Shorter Oxford Textbook of Psychiatry, 6th Ed.

CHAPTER 17. The misuse of alcohol and drugs

Introduction

Classification of substance use disorders

Alcohol-related disorders

Other substance use disorders

Introduction

The presentation of alcohol and drug misuse is not limited to any particular psychiatric or indeed medical specialty. Alcohol and drug use may play an important part in all aspects of psychiatric practice, and is relevant, for example, to the assessment of a patient with acute confusion on a medical ward, a suicidal patient in the Accident and Emergency department, an elderly patient whose self-care has deteriorated, a troubled adolescent, or a disturbed child who may be inhaling volatile substances.

The phrases substance use disorder (DSM-IV) or disorders due to psychoactive drug use (ICD-10) are used to refer to conditions arising from the misuse of alcohol, psychoactive drugs, or other chemicals such as volatile substances. In this chapter, problems related to alcohol will be discussed first under the general heading of alcohol use disorders. Problems related to drugs and other chemicals will then be discussed under the general heading of other substance use disorders.

Classification of substance use disorders

The two classification systems, DSM-IV and ICD-10, use similar categories for substance use disorders but group them in different ways. Both schemes recognize the following disorders: intoxication, abuse (or harmful use), dependence, withdrawal states, psychotic disorders, and amnestic syndromes. These and some additional categories are shown in Table 17.1.

In both diagnostic systems the first step in classification is to specify the substance or class of substance that is involved (see Table 17.2); this provides the primary diagnostic category. Although many drug users take more than one kind of drug, the diagnosis of the disorder is made on the basis of the most important substance used. Where this judgement is difficult or where use is chaotic and indiscriminate, the categories polysubstance-related disorder(DSM-IV) or disorder due to multiple drug use (ICD-10) may be employed. Then the relevant disorder listed in Table 17.1 is added to the substance misused. In this system any kind of disorder can, in principle, be attached to any drug, although in practice certain disorders do not develop with individual drugs. ICD-10 also has a specific category, residual and late-onset psychotic disorder, which describes physiological or psychological changes that occur when a drug is taken but then persist beyond the period during which a direct effect of the substance would reasonably be expected to be operating. Such categories might include hallucinogen-induced flashbacks and alcohol-related dementia.

Definitions in DSM-IV and ICD-10

Intoxication

Both DSM-IV and ICD-10 provide definitions of intoxication. In both systems, intoxication is considered to be a transient syndrome due to recent substance ingestion that produces clinically significant psychological and physical impairment. These changes disappear when the substance is eliminated from the body. The nature of the psychological changes varies with the individual as well as with the drug—for example, some people when intoxicated with alcohol become aggressive, while others become maudlin.

Table 17.1 Substance-related disorders

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Table 17.2 Classes of substances

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Table 17.3 Criteria for substance abuse (DSM-IV) and harmful use (ICD-10)

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Abuse

The terms abuse in DSM-IV and harmful use in ICD-10 refer to maladaptive patterns of substance use that impair health in a broad sense (see Table 17.3). (The widely used term misuse carries a similar meaning.) The DSM and ICD criteria differ somewhat, with the emphasis being on negative social consequences of substance use in DSM-IV, and on adverse physical and psychological consequences in ICD-10. Some individuals show definite evidence of substance abuse but do not meet the criteria for substance dependence (see Table 17.4). However, if they do meet those criteria, the diagnosis of dependence should be made, not that of abuse or harmful use.

Dependence

The term dependence refers to certain physiological and psychological phenomena that are induced by the repeated taking of a substance. The criteria for diagnosing dependence are similar in DSM-IV and ICD-10, and include the following:

• a strong desire to take the substance

• progressive neglect of alternative sources of satisfaction

• the development of tolerance

• a physical withdrawal state (see Table 17.4).

Tolerance

This is a state in which, after repeated administration, a drug produces a decreased effect, or increasing doses are required to produce the same effect.

Table 17.4 Criteria for dependence in DSM-IV and ICD-10

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Withdrawal state

This refers to a group of symptoms and signs that occur when a drug is reduced in amount or withdrawn, which last for a limited time. The nature of the withdrawal state is related to the class of substance used.

Alcohol-related disorders

Terminology

Alcoholism. In the past, the term alcoholism was generally used in medical writing. Although the word is still widely used in everyday language, it is unsatisfactory as a technical term because it has more than one meaning. It can be applied to habitual alcohol consumption that is deemed excessive in amount according to some arbitrary criterion, and it may also refer to damage, whether mental, physical, or social, resulting from such excessive consumption. In a more specialized sense, alcoholism may imply a specific disease entity that is supposed to require medical treatment. However, to speak of an alcoholic often has a pejorative meaning, suggesting behaviour that is morally bad. For most purposes it is better to use four terms that relate to the classifications outlined above.

1Excessive consumption of alcohol. This refers to a daily or weekly intake of alcohol that exceeds a specified amount (see below). Excessive consumption of alcohol is also known as hazardous drinking. Harmful drinking is a term used to describe levels of hazardous drinking at which damage to health is very likely.

2Alcohol misuse. This refers to drinking that causes mental, physical, or social harm to an individual. However, it does not include those with formal alcohol dependence.

3Alcohol dependence. This term can be used when the criteria for a dependence syndrome listed in Table 17.4 are met.

4Problem drinking. This term is applied to those in whom drinking has caused an alcohol-related disorder or disability. Its meaning is essentially similar to alcohol misuse, but it can also include drinkers who are dependent on alcohol.

The term alcoholism, if it is used at all, should be regarded as a shorthand way of referring to some combination of these four conditions. However, since these specific terms have been introduced fairly recently, the term alcoholism has been used in this chapter when referring to the older literature.

At this point it is appropriate to examine the moral and medical models of alcohol misuse.

The moral and medical models

According to the moral model, if someone drinks too much, they do so of their own free will, and if their drinking causes harm to them or their family, their actions are morally bad. The corollary of this attitude is that public drunkenness should be punished. In many countries this is the official practice; public drunks are fined, and if they cannot pay the fine they go to prison. Many people now believe that this approach is too harsh and unsympathetic. Whatever the humanitarian arguments, there is little practical justification for punishment, since there is little evidence that it influences the behaviour of dependent drinkers. However, it is possible that social disapproval could play a role in dissuading non-dependent drinkers from excessive consumption.

According to the medical model, a person who misuses alcohol is ill rather than wicked. Although it had been proposed earlier, this idea was not strongly advocated until 1960, when Jellinek published an influential book, The Disease Concept of Alcoholism. The disease concept embodies three basic ideas.

1. Some people have a specific vulnerability to alcohol misuse.

2. Excessive drinking progresses through well-defined stages, at one of which the person can no longer control their drinking.

3. Excessive drinking may lead to physical and mental disease of several kinds.

One of the main consequences of the disease model is that attitudes towards excessive drinking become more humane. Instead of blame and punishment, medical treatment is provided. The disease model also has certain disadvantages. By implying that only certain people are at risk, it diverts attention from some important facts. First, anyone who drinks a great deal for a long time may become dependent on alcohol. Secondly, the best way to curtail the misuse of alcohol may be to limit consumption in the whole population, and not just among a predisposed minority. Thirdly, it may suggest that excessive drinking, at least initially, is not a product of a personal choice.

Perhaps a useful way to resolve these two approaches is to apply the moral model to excessive drinking in the population in the hope of decreasing the number of people who put themselves at risk of alcohol-related disability. However, once dependence has occurred, with its attendant loss of control over drinking, a medical approach may be more appropriate.

Excessive alcohol consumption

In many societies the use of alcohol is sanctioned and even encouraged by sophisticated marketing techniques. Therefore the level of drinking at which an individual is considered to demonstrate excessive alcohol consumption is a somewhat arbitrary concept, which is usually defined in terms of the level of use associated with significant risk of alcohol-related health and social problems. It is usually expressed in units of alcohol consumed per week. For example, in the UK, current government advice is that men should not drink more than 3–4 units of alcohol a day, while for women the limit is 2–3 units a day. Above these limits the risk of health and social problems increases generally in proportion to the amount of alcohol consumed. Men who regularly drink more than 50 units a week and women who regularly drink more than 35 units a week are seen as harmful drinkers (Department of Health, 2007a).

If the concept of excessive alcohol consumption is to be understood and accepted, it is necessary to explain the units in which it is assessed. In everyday life, this is done by referring to conventional measures such as pints of beer or glasses of wine. These measures have the advantage of being widely understood, but they are imprecise because both beers and wines vary in strength (see Table 17.5). Alternatively, consumption can be measured as the amount of alcohol (expressed in grams). This measure is precise and useful for scientific work, but is difficult for many people to relate to everyday measures.

For this reason, the concept of a unit of alcohol has been introduced for use in health education. A unit can be related to everyday measures because it corresponds to half a pint of beer, one glass of table wine, one conventional glass of sherry or port, and one single bar measure of spirits. It can also be related to average amounts of alcohol (see Table 17.5). Thus on this measure a can of beer (450 ml) contains nearly 1.5 units, a bottle of table wine contains about 10 units, a bottle of spirits contains about 30 units, and 1 unit is about 8 g of alcohol. The increase in strength of wine and beer over the last two decades has made many of these calculations difficult. Wine sold in the UK now contains an average of 12–13% alcohol, and sometimes more. To compound matters, the size of wine glass used in most restaurants has increased from 125 ml to 175 ml, so that an average serving in a restaurant or public house is equivalent to a minimum of 2 units.

Epidemiological aspects of excessive drinking and alcohol misuse

Epidemiological methods can be applied to the following questions concerning excessive drinking and alcohol misuse.

1. What is the annual per capita consumption of alcohol for a nation as a whole, and how does this vary over the years and between nations?

2. What is the pattern of alcohol use of different groups of people within a defined population?

3. How many people in a defined population misuse alcohol?

4. How does alcohol misuse vary with such characteristics as gender, age, occupation, social class, and marital status?

Unfortunately, we lack reliable answers to these questions, partly because different investigators have used different methods of defining and identifying alcohol misuse and ‘alcoholism’, and partly because excessive drinkers tend to be evasive about the amount that they drink and the symptoms that they experience.

Consumption of alcohol in different countries

In the UK, the annual consumption of alcohol per adult (calculated as absolute ethanol consumption) doubled between 1960 and 2000, rising from about 4 litres to over 8 litres. Consumption in Western Europe has generally been higher than this, particularly in France. High levels of consumption are also seen in the former Soviet Union, while in the Eastern Mediterrean and in Muslim countries consumption is much less.

Recent changes in the UK can be usefully considered in a historical perspective. For example, in Great Britain between 1860 and 1900 the annual consumption of alcohol was about 10 litres of absolute alcohol per head of population over 15 years of age. It then fell until the early 1930s, reaching about 4 litres per person over 15 years of age per annum. Consumption then increased slowly until the 1950s, when it began to rise more rapidly. Over the last few years there has been a small drop in annual consumption, but the average annual amount is still about twice what it was in the 1950s (see Figure 17.1).

Table 17.5 Alcohol content of some beverages

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Figure 17.1 Average annual consumption of alcohol in the UK between 1947 and 2009. Source: British Beer and Pub Association (2010). BBPA Statistical Handbook, 2010. British Beer and Pub Association, London.

These changes have been accompanied by changes in the kinds of alcoholic beverages consumed. In Britain in 1900, beer and spirits accounted for most of the alcohol that was drunk. By 1980 the consumption of wine had risen about fourfold, and accounted for almost as much of the consumption of alcohol as did spirits, although most alcohol was still consumed as beer (see Figure 17.1).

Drinking habits in different groups. Surveys of drinking behaviour generally depend on self-reports, a method which is open to obvious errors. Enquiries of this kind have been conducted in several countries, including the UK and the USA. Such studies show that the highest reported consumption of alcohol is generally among young men who are unmarried, separated, or divorced. However, over the last 15 years drinking by women has increased. Based on population estimates in 2008, men in England drank on average 16.8 units of alcohol a week, whereas women drank on average 8.6 units per week. Around 18% of school pupils aged 11 to 15 years reported drinking alcohol in the week prior to interview; this figure is lower than that for 2001, when 26% of pupils reported drinking in the preceding week (Office for National Statistics, 2010).

The prevalence of alcohol misuse

This can be estimated in three ways—from hospital admission rates, from deaths from alcoholic cirrhosis, and by surveys of the general population.

Hospital admission rates. These give an inadequate measure of prevalence, because a large proportion of excessive drinkers are not admitted to hospital.

• In England during the period 2007–2008 there were about 62 000 NHS hospital admissions with a primary diagnosis of mental and behavioural disorders due to alcohol (Office for National Statistics, 2009).

• Alcohol is estimated to be a causal factor in about one-third of attendances at Accident and Emergency services (Academy of Medical Sciences, 2004).

Deaths from alcoholic cirrhosis. About 10–20% of people who drink alcohol excessively develop cirrhosis of the liver, and there are correlations in a population between rates of liver cirrhosis and mean alcohol consumption. Therefore deaths from cirrhosis can be used as a means of estimating rates of alcohol misuse. Rates of mortality from liver cirrhosis are showing a decline in a number of developed countries. For example, in southern Europe there has been a sustained decrease in deaths from cirrhosis, probably as a result of fiscal law enforcement and health promotion policies. On the other hand, alcoholic liver cirrhosis appear to be increasing in England, with deaths attributable to this cause rising from 3236 in 2001 to 4400 in 2008, an increase of 36% (Office for National Statistics, 2010).

General population surveys. One method of ascertaining the rate of alcohol misuse in a population is by seeking information from general practitioners, social workers, probation officers, health visitors, and other agencies who are likely to come into contact with heavy drinkers. Another approach is the community survey, in which samples of people are asked about the amount they drink and whether they experience symptoms. For example, the National Survey Comorbidity Replication in the USA found a 1-year prevalence rate for DSM-IV alcohol abuse of 3.1%, while the prevalence of alcohol dependence was 1.3% (Kessler et al., 2005b). The Psychiatric Morbidity Survey in England, reporting 6-month prevalences, classified 24% of adults living in households as hazardous drinkers, and 6% as alcohol dependent (although 5% of these individuals were classified as having ‘mild’ dependence) (McManus et al., 2007). Over time there are significant individual fluctuations in alcohol consumption, with a substantial proportion of people moving from hazardous drinking towards safer drinking, while others move into the hazardous drinking category.

Surveys based on households are likely to miss certain groups at high risk of alcohol misuse and dependence. The British Psychiatric Morbidity Survey sampled separately from homeless populations and from those in institutions such as prisons. Among people living in night shelters or sleeping rough, 40% were found to drink more than 50 units of alcohol a week, and about 35% of those sleeping rough were estimated to have severe alcohol dependence (Gill et al., 1996).

Alcohol misuse and population characteristics

Gender. Rates of alcohol misuse and dependence are consistently higher in men than in women, but the ratio of affected men to women varies markedly across cultures. In Western countries, about three times as many men as women suffer from alcohol misuse and dependence, but in Asian and Hispanic cultures a higher ratio of men to women are affected. In the Psychiatric Morbidity Survey in England the rate of hazardous drinking among white men (36%) was more than twice as high as that among white women (16%), while the rate among South Asian men (12%) was four times higher than that among South Asian women (3%) (McManus et al., 2007). However, perhaps because of changing social attitudes, the gap between men and women with regard to excessive drinking seems to be narrowing in many Western countries. This is of concern because studies indicate that women are more susceptible than men to many of the damaging effects of alcohol (see below).

Age. We have seen that the heaviest drinkers are men in their late teens or early twenties. In most cultures the prevalence of alcohol misuse and dependence is lower in those aged over 45 years.

Ethnicity and culture. The followers of certain religions which proscribe alcohol (e.g. Islam, Hinduism, and the Baptist Church) are less likely than the general population to misuse alcohol. It is also worth noting that the non-white population in the UK and the USA are less likely to drink excessively than the white population, and therefore have a lower rate of alcohol-related disorders. In some instances, the low consumption of alcohol in a particular ethnic group may be due to a biologically determined lack of tolerance to alcohol. For example, Asians with a particular variant of the isoenzyme of aldehyde dehydrogenase experience flushing, nausea, and tachycardia due to accumulation of acetaldehyde when they drink alcohol. Such individuals are likely to be at reduced risk of excess drinking and the consequent development of alcohol-related disorders. Thus, although the aldehyde dehydrogenase variant that causes the flushing reaction was present in 35% of the general Japanese population, it was found in only 7% of Japanese patients with alcoholic liver disease (Shibuya and Yoshida, 1988).

Occupation. The risk of alcohol misuse is much increased among several occupational groups. These include chefs, kitchen porters, barmen, and brewery workers, who have easy access to alcohol, executives and salesmen who entertain on expense accounts, actors and entertainers, seamen, and journalists. Doctors have been said to have an increased risk of harmful drinking, but whether this is in fact the case has been questioned. However, doctors do have higher rates of prescription drug misuse, and treatment programmes for both this problem and alcohol-related disorders may be difficult to institute (Marshall, 2008).

Syndromes of alcohol dependence and alcohol withdrawal

Patients are described as alcohol dependent when they meet the criteria for substance dependence described in Table 17.4. The presence of withdrawal phenomena is not necessary for the diagnosis of dependence, and a substantial minority of individuals who meet the dependence criteria do not experience any withdrawal phenomena when their intake of alcohol decreases or stops. However, about 5% of dependent individuals experience severe withdrawal symptomatology, including delirium tremens and grand mal seizures.

Course of alcohol misuse and dependence

Schuckit et al. (1993) reviewed the course of over 600 men with alcohol dependence who received inpatient treatment at a single facility in the USA between 1985 and 1991. These individuals showed a general pattern of escalation of heavy drinking in their late twenties followed by evidence of serious difficulties in work and social life by their early thirties. In their middle to late thirties, following the perception that they could not control their drinking, they experienced increasing social and work-related problems, together with a significant deterioration in physical health.

Vaillant (2003) described a 60-year follow-up of 194 men who had exhibited misuse of alcohol at some point in their adult life. By the age of 70 years over 50% of the cohort had died and about 20% were abstinent. Around 10% were drinking in a controlled way, while a further 10% continued to misuse alcohol. In a number of individuals alcohol misuse had apparently persisted for decades without remission, death, or progression to formal dependence. However, for alcohol-dependent men, periods of controlled drinking were invariably followed by a return to a pattern of alcohol dependence. Attendance at Alcoholics Anonymous was the best predictor of good outcome. This study suggests that the prognosis of alcohol misuse is very variable. However, once an individual has become alcohol dependent the prognosis is poor unless abstinence can be maintained.

The alcohol withdrawal syndrome

Withdrawal symptoms occur across a spectrum of severity, ranging from mild anxiety and sleep disturbance to the life-threatening state known as delirium tremens. The symptoms generally occur in people who have been drinking heavily for years and who maintain a high intake of alcohol for weeks at a time. The symptoms follow a drop in blood alcohol concentration. They characteristically appear on waking, after the fall in concentration has occurred during sleep. Dependent drinkers often take a drink on waking to stave off withdrawal symptoms. In most cultures, early-morning drinking is diagnostic of dependency. With the increasing need to stave off withdrawal symptoms during the day, the drinker typically becomes secretive about the amount consumed, hides bottles, or carries them in a pocket. Rough cider and cheap strong beers may be drunk regularly in order to obtain the most alcohol for the minimum cost.

The earliest and commonest feature of alcohol withdrawal is acute tremulousness affecting the hands, legs, and trunk (‘the shakes’). The sufferer may be unable to sit still, hold a cup steady, or fasten up buttons. They are also agitated and easily startled, and often dread facing people or crossing the road. Nausea, retching, and sweating are frequent. Insomnia is also common. If alcohol is taken, these symptoms may be relieved quickly; otherwise they may last for several days (see Table 17.6).

Table 17.6 Symptoms and signs of acute alcohol withdrawal

Anxiety, agitation, and insomnia

Tachycardia and sweating

Tremor of limbs, tongue and eyelids

Nausea and vomiting

Seizures

Confusion and hallucinations

From Ritson (2005).

As withdrawal progresses, misperceptions and hallucinations may occur, usually only briefly. Objects appear distorted in shape, or shadows seem to move; disorganized voices, shouting, or snatches of music may be heard. Later there may be epileptic seizures, and finally after about 48 hours delirium tremens may develop.

Other alcohol-related disorders

The different types of damage—physical, psychological, and social—that can result from alcohol misuse are described in this section. A person who suffers from these disabilities may or may not be suffering from alcohol dependence.

Physical damage

Excessive consumption of alcohol may lead to physical damage in several ways. First, it can have a direct toxic effect on certain tissues, notably the brain and liver. Secondly, it is often accompanied by poor diet, which may lead to deficiency of protein and B vitamins. Thirdly, it increases the risk of accidents, particularly head injury. Fourthly, it is accompanied by general neglect which can lead to increased susceptibility to infection.

Gastrointestinal disorders

Gastrointestinal disorders are common, notably liver damage, gastritis, peptic ulcer, oesophageal varices, and acute and chronic pancreatitis. Damage to the liver, including fatty infiltration, hepatitis, cirrhosis, and hepatoma, is particularly important. For a person who is dependent on alcohol, the risk of dying from liver cirrhosis is almost ten times greater than the average. However, only about 10–20% of alcohol-dependent people develop cirrhosis.

Nervous system

Alcohol also damages the nervous system. Neuropsychiatric complications are described later; other neurological conditions include peripheral neuropathy, epilepsy, and cerebellar degeneration. The last of these is characterized by unsteadiness of stance and gait, with less effect on arm movements or speech. Rare complications are optic atrophy, central pontine myelinolysis, and Marchiafava–Bignami syndrome. The latter condition results from widespread demyelination of the corpus callosum, optic tracts, and cerebellar peduncles. Its main features are dysarthria, ataxia, epilepsy, and marked impairment of consciousness; in the more prolonged forms, dementia and limb paralysis occur. Head injury is also common in alcohol-dependent people.

Cardiovascular system

Alcohol misuse is associated with hypertension and increased risk of stroke. Paradoxically, men who drink moderate amounts of alcohol (up to about 10 units a week) appear to be less likely than non-drinkers to die from coronary artery disease (Beulens et al., 2010). Alcohol misuse has also been linked to the development of certain cancers, notably of the mouth, pharynx, oesophagus, liver, and breast.

Other physical complications of excessive consumption of alcohol are too numerous to detail here. Examples include anaemia, myopathy, episodic hypoglycaemia, haemochromatosis, cardiomyopathy, vitamin deficiencies, and tuberculosis. They are described in textbooks of medicine, such as the Oxford Textbook of Medicine (Warrell et al., 2010).

Alcohol misuse in women

Studies suggest that women progress more rapidly than men to problem drinking, and tend to suffer the medical consequences of alcohol use after a shorter period of exposure to a smaller amount of alcohol. As well as the expected medical complications noted above, female drinkers also show elevated rates of breast cancer and reproductive pathology, including amenorrhoea, anovulation, and possibly early menopause.

Damage to the fetus

There is evidence that a fetal alcohol syndrome occurs in children born to mothers who drink excessively. In France, Lemoine et al. (1968) described a syndrome of facial abnormality, small stature, low birth weight, low intelligence, and overactivity. Fetal alcohol syndrome is associated with clearly excessive alcohol use during pregnancy. However, subsequent research has suggested that even moderate or low levels of alcohol consumption at this time can have adverse effects on childhood development, and the ‘safe limit’ for alcohol consumption during pregnancy (if such a level exists) is not known. Current advice is that women should avoid alcohol during the first 12 weeks of pregnancy, and thereafter consume no more than one to two drinks a week (Khalil and O’Brien, 2010).

Mortality

People with a low level of alcohol consumption (about 1 unit daily) have decreased mortality rates compared with non-drinkers (Doll et al., 2005). This is mainly attributable to lowered cardiovascular mortality (see above). Not surprisingly, however, the mortality rate is increased in those who misuse alcohol. Follow-up investigations have studied mainly middle-aged men drinking excessively, in whom overall mortality is at least twice the expected rate, and mortality in women who drink excessively appears to be substantially higher than this (Harris and Barraclough, 1998). In England it has been estimated that about 15 000 deaths a year are directly attributable to the medical consequences of alcohol misuse (Office for National Statistics, 2010). Of course, alcohol must contribute indirectly to many more deaths from causes such as accidents. At a global level, the World Health Organization has estimated that alcohol causes 1.8 million deaths annually (about 3.2% of all deaths).

Psychiatric disorders

Alcohol-related psychiatric disorders fall into four groups:

• intoxication phenomena

• withdrawal phenomena

• toxic or nutritional disorders

• associated psychiatric disorders.

Intoxication phenomena

The severity of the symptoms of alcohol intoxication correlates approximately with the blood alcohol concentration. As noted above, there is much individual variation in the psychological effects of alcohol, but certain reactions, such as lability of mood and belligerence, are more likely to cause social difficulties. At high doses, alcohol intoxication can result in serious adverse effects, such as falls, respiratory depression, inhalation of vomit, and hypothermia.

The molecular mechanisms that underlie the acute effects of alcohol are unclear. An influential view has been that alcohol interacts with neuronal membranes to increase their fluidity—an action also ascribed to certain anaesthetic agents. This action gives rise to more specific changes in the release of a range of neurotransmitters, leading to the characteristic pharmacological actions of alcohol. For example, the pleasurable effects of alcohol use could be mediated by release of dopamine and opioids in the mesolimbic forebrain, while the anxiolytic effects could reflect facilitation of brain gamma-aminobutyric acid (GABA) activity (Lingford-Hughes et al., 2010).

The term idiosyncratic alcohol intoxication has been applied to marked maladaptive changes in behaviour, such as aggression, occurring within minutes of taking an amount of alcohol insufficient to induce intoxication in most people (with the behaviour being uncharacteristic of the affected individual). In the past, these sudden changes in behaviour were called pathological drunkenness, or manie à potu, and the descriptions emphasized the explosive nature of the outbursts of aggression. However, there is doubt as to whether behaviour of this kind really is induced by small amounts of alcohol. The term ‘idiosyncratic alcohol intoxication’ does not appear in DSM-IV or ICD-10.

Memory blackouts or short-term amnesia are frequently reported after heavy drinking. At first the events of the night before are forgotten, even though consciousness was maintained at the time. Such memory losses can occur after a single episode of heavy drinking in people who are not dependent on alcohol. If they recur regularly, they indicate habitual excessive consumption. With sustained excessive drinking, memory losses may become more severe, affecting parts of the daytime or even whole days.

Withdrawal phenomena

The general withdrawal syndrome has been described earlier under the heading of alcohol dependence. Here we are concerned with the more serious psychiatric syndrome of delirium tremens. Delirious states are described generally in Chapter 13, but delirium tremens is discussed here because of its prevalence and mortality, and its somewhat different treatment.

Delirium tremens occurs in people whose history of alcohol misuse extends over several years. Following alcohol withdrawal there is a dramatic and rapidly changing picture of disordered mental activity, with clouding of consciousness, disorientation in time and place, and impairment of recent memory. Perceptual disturbances include misinterpretations of sensory stimuli and vivid hallucinations, which are usually visual but sometimes occur in other modalities. There is severe agitation, with restlessness, shouting, and evident fear. Insomnia is prolonged. The hands are grossly tremulous and sometimes pick up imaginary objects; truncal ataxia may occur. Autonomic disturbances include sweating, fever, tachycardia, raised blood pressure, and dilatation of pupils. Dehydration and electrolyte disturbance are characteristic. Blood testing shows leucocytosis and impaired liver function.

The condition lasts for 3 or 4 days, with the symptoms characteristically being worse at night. It often ends with deep prolonged sleep from which the patient awakens with no symptoms and little or no memory of the period of delirium. Delirium tremens carries a significant risk of mortality and should be regarded as a medical emergency.

Toxic or nutritional conditions

These include Korsakov’s psychosis and Wernicke’s encephalopathy (see also Chapter 13), and alcoholic dementia, which is described next.

Alcoholic dementia. In the past there has been disagreement as to whether alcohol misuse can cause dementia. This doubt may have arisen because patients with general intellectual defects have been wrongly diagnosed as having Korsakov’s psychosis. However, it is now generally agreed that chronic alcohol misuse can cause cognitive impairment, particularly in tests of memory and executive function (Sullivan et al., 2010).

Attention has also been directed to the related question of whether chronic alcohol misuse can cause structural brain atrophy. Both computerized tomography (CT) scanning and magnetic resonance imaging (MRI) have shown that excess alcohol consumption is associated with enlarged lateral ventricles. Furthermore, MRI scans have shown focal deficits, with loss of grey matter in both cortical and subcortical areas. Subcortical changes are more likely to be found in patients with Korsakov’s syndrome. Thinning of the corpus callosum has also been reported in patients with alcohol dependence. White matter changes are common in heavy drinkers, and studies using diffusion tensor imaging (see p. 112) indicate that there is demyelination.

Many of the changes noted above occur in patients without obvious neurological disturbance, although, as noted above, psychological testing usually reveals deficits in cognitive function. The changes in brain structure and cognitive impairment that are seen in excessive drinkers remit to some extent with cessation of alcohol use. However, some abnormalities can still be detected after long periods of abstinence.

For a review of brain imaging studies of the effects of alcohol, see Sullivan et al. (2010).

Associated psychiatric disorder

Personality deterioration. As the patient becomes increasingly concerned with the need to obtain alcohol, interpersonal skills and attention to their usual interests and responsibilities may deteriorate. These changes in social and interpersonal functioning should not be confused with personality disorder, which should be diagnosed only when the appropriate features have been clearly present prior to the development of alcohol dependence.

Mood and anxiety disorders. The relationship between alcohol consumption and mood is complex. On the one hand, some depressed and anxious patients drink excessively in an attempt to improve their mood. On the other hand, excess drinking may induce persistent depression or anxiety. People with a history of alcohol dependence have a fourfold increased risk of experiencing subsequent major depression, and the risk remains elevated even in those who are no longer drinking. The risk of experiencing an anxiety disorder is also significantly increased, but to a somewhat lesser extent (Anthenelli, 2010).

Suicidal behaviour. Suicide rates among people with alcohol use disorders are much higher than those among individuals who do not misuse alcohol. Conner and Duberstein (2004) identified a number of risk factors for suicidal behaviour among people with alcohol dependence, including impulsivity, negative affect, and hopelessness. Suicide among alcohol misusers is discussed further on p. 424. Here it is worth noting that suicide in young men is associated with a high rate of substance misuse, including alcohol misuse.

Pathological jealousy. Excessive drinkers may develop an overvalued idea or delusion that their partner is being unfaithful. This syndrome of pathological jealousy is described on p. 305.

Alcoholic hallucinosis. This is characterized by auditory hallucinations, usually involving voices uttering insults or threats, which occur in clear consciousness. The patient is usually distressed by these experiences, and appears anxious and restless. The hallucinations are not due to acute alcohol withdrawal, and can indeed persist after several months of abstinence. There has been considerable controversy about the aetiology of the condition. Some follow Kraepelin and Bonhoffer in regarding it as a rare organic complication of alcoholism; others follow Bleuler in supposing that it is related to schizophrenia. More recent reviewers have concluded that alcoholic hallucinosis is an alcohol-induced organic psychosis, which is distinct from schizophrenia and has a good prognosis if abstinence can be maintained (Mann and Kiefer, 2009).

In both DSM-IV and ICD-10, alcoholic hallucinosis is subsumed under the heading of substance-induced psychotic disorder.

Social damage (see Box 17.1)

Family problems

Excessive drinking is liable to cause profound social disruption, particularly in the family. Marital (or other relationship) and family tension is virtually inevitable. The divorce rate among heavy drinkers is high, and the partners of men who drink excessively are likely to become anxious, depressed, and socially isolated. The husbands of ‘battered wives’ frequently drink excessively, and some women who are admitted to hospital because of self-poisoning blame their partner’s drinking. The home atmosphere is often detrimental to any children present, because of quarrelling and violence, and a drunken parent provides a poor role model. Children of heavy drinkers are at risk of developing emotional or behavioural disorders, and of performing poorly at school.

Box 17.1 Medical and social consequences of excessive alcohol consumption in the UK

1. Annual alcohol-related costs of crime and public disorder are £7.3 billion, workplace costs are £6.4 billion, and health costs are £1.7 billion.

2. Up to one-third of all Accident and Emergency attendances involve alcohol.

3. Around 2.9 million (7%) of the adult population are dependent on alcohol.

4. Around 47% of victims of violence believe that their assailant was under the influence of alcohol.

5. Alcohol is involved in 30–60% of child protection cases. Up to 1.3 million children are adversely affected by family drinking.

Source: Prime Minister’s Strategy Unit (2003).

Work difficulties and road accidents

At work, the heavy drinker often progresses through declining efficiency, lower-grade jobs, and repeated dismissals to lasting unemployment. There is also a strong association between road accidents and alcohol misuse. The strength of the association varies between countries. For example, in 2006, the proportion of fatal traffic accidents involving alcohol was about 17% in the UK, whereas the corresponding figures for France and Germany were about 27% and 11%, respectively. Whether these figures are attributable to real cross-national differences in the role of alcohol in traffic fatalities, or whether they are due to variations in methods of data collection and definition, is not certain (Assum and Sørensen, 2010).

Crime

Excessive drinking is also associated with crime, mainly petty offences such as larceny, but also with fraud, sexual offences, and crimes of violence, including murder. Studies of recidivist prisoners in England and Wales have shown that many of them had serious drinking problems before imprisonment. It is not easy to determine to what extent alcohol causes the criminal behaviour and to what extent it is part of the lifestyle of the criminal. In addition, there is a link between certain forms of alcohol misuse and antisocial personality disorder (see below).

The causes of excessive drinking and alcohol misuse

Despite much research, surprisingly little is known about the causes of excessive drinking and alcohol dependence. At one time it was believed that certain people were particularly predisposed, either through personality or due to an innate biochemical anomaly. Nowadays this simple notion of specific predisposition is no longer held. Instead, alcohol misuse is thought to result from a variety of interacting factors which can be divided into individual factors and those in society.

Individual factors

Genetic factors

Most genetic studies of alcoholism have investigated individuals with evidence of alcohol dependence. If less severe diagnostic criteria are involved—for example, fairly broadly defined alcohol misuse—the relative genetic contribution is somewhat less. However, it is well established that alcohol dependence aggregates in families, and twin studies show a higher concordance in MZ than DZ twins, with an estimated heritability of about 50% (Bienvenu et al., 2011).

Support for a genetic explanation also comes from investigations of adoptees. A number of studies have indicated a higher risk of alcohol misuse and dependence in the adopted-away sons of alcohol-dependent biological parents than in the adopted-away sons of non-alcohol-dependent biological parents. Such studies suggest a genetic mechanism, but they do not indicate its nature.

Adoption studies in Sweden led to the suggestion that there are two separate kinds of alcohol dependence, which have been called type 1 and type 2 (Cloninger et al., 1988). Type 2 alcoholism is strongly genetic, predominantly occurs in males, has an early age of onset, and is associated with criminality and sociopathic disorder in both adoptee and biological father. By contrast, type 1 alcoholism has a later age of onset, is only mildly genetic, and occurs in both men and women. Subsequent typologies of alcohol dependence have become more complex, but continue to include a group of alcohol-dependent people with early age of onset and sociopathic disorder. In others, however, an early age of onset of alcohol dependence is associated not with sociopathic traits but with high levels of anxiety-related symptoms(Leggio et al., 2009).

If a genetic component to aetiology were to be confirmed, it would still be necessary to discover the mechanism. The latter might be biochemical, involving the metabolism of alcohol or its central effects, or psychological, involving personality. In addition, it is important to note that a predisposition to misuse alcohol and develop dependence will only be expressed if a person consumes excessive amounts of alcohol. Here non-genetic familial factors are likely to play a major role.

Genes for alcohol dependence risk. Allelic association studies have focused in particular on the alleles of genes that affect alcohol metabolism because, as we have already seen, people with impaired activity of the alcohol-metabolizing enzyme, aldehyde dehydrogenase, have unpleasant reactions when they consume alcohol, and are therefore at significantly lower risk of alcohol dependence. At a molecular level, a point mutation in the gene for a form of aldehyde dehydrogenase (ALDH2) renders the enzyme inactive; this mutation is less common in people with alcohol dependence. Subsequent linkage analyses have confirmed that mutations in the genes that code for aldehyde dehydrogenase protect against harmful drinking (Foroud et al., 2010). However, such mutations are rare in people of European ancestry. Other candidate genes have included the dopamine D4 receptor and the GABA receptor, and some associations with alcohol dependence have been reported. However, attempts at replication have yielded inconsistent findings. Similarly, genome-wide association studies (GWAS) have not provided reliable indications of relevant genes, although again the GABA receptor has been implicated by some (Foroud et al., 2010).

Other biological factors

The sons of men with alcohol dependence are at increased risk of developing alcohol dependence themselves, and a number of studies have attempted to find biological abnormalities that may antedate and predict the development of alcohol dependence in these individuals. A variety of impairments have been described, including impaired performance on cognitive tasks, particularly executive function, and an abnormal P300 visual evoked response, which is a measure of visual information processing. There is also reasonably consistent evidence that sons of alcohol-dependent men are less sensitive to the acute intoxicating effects of alcohol. Presumably, if people experience less subjective response to alcohol, they may tend to drink more, thus putting themselves at risk of developing alcohol dependence. However, the evidence for this interesting hypothesis is inconsistent (Sher et al., 2005).

Learning factors

Alcohol use. Children tend to follow their parents’ drinking patterns, and from an early age boys tend to be encouraged to drink more than girls. Non-genetic familial factors appear to be important in determining levels of alcohol use. Nevertheless, it is not uncommon to meet people who are abstainers although their parents drank heavily. In addition, the risk of children of alcohol-dependent parents developing alcohol use disorders is apparently little influenced by whether their parents are currently drinking or not. This suggests that modelling of drinking behaviour does not contribute substantially to the increased risk in the children (Sher et al., 2005)

Reward dependence. It has also been suggested that learning processes may contribute in a more specific way to the development of alcohol dependence. Thus the ability of alcohol to increase pleasurable feelings and decrease anxiety could lead to behavioural reinforcement, particularly in people who for physiological or social reasons overemphasize the positive effects of alcohol while ignoring its negative consequences. Recent formulations that combine biochemical and cognitive approaches emphasize the role of dopamine release in mesolimbic pathways in mediating incentive learning. In this way drugs such as alcohol which increase dopamine levels in this brain region stimulate motivational behaviours that are focused on the need to secure further drug supplies. These behaviours may be outside conscious control, and are difficult to extinguish (Lingford-Hughes et al., 2010).

Personality factors

Little progress has been made in identifying personality factors that contribute to alcohol misuse and dependence. In clinical practice it is common to find that excessive alcohol consumption is associated with chronic anxiety, a pervading sense of inferiority, or self-indulgent tendencies. However, many people with personality problems of this kind do not resort to excessive drinking or become alcohol dependent. Other surveys have emphasized the role of personality traits that lead to risk taking and novelty seeking (Kampov-Polevoy et al., 2004). It seems likely that these characteristics apply to those with antisocial personality disorder, who are known to be at increased risk of misusing alcohol and developing alcohol dependence. However, the majority of alcohol-dependent people do not have an antisocial personality disorder.

Psychiatric disorder

Alcohol misuse is commonly found in conjunction with other psychiatric disorders, and sometimes appears to be secondary to them. For example, some patients with depressive disorders use alcohol in the mistaken hope that it will alleviate low mood. Those with anxiety disorders, particularly panic disorder and social phobia, are also at risk. Alcohol misuse is also seen in patients with bipolar disorder and schizophrenia. The mechanisms underlying this comorbidity are not established, but overlapping genetic predispositions are a possibility, perhaps associated with shared abnormalities in the functioning of reward pathways (Negrete and Gill, 2009). (The treatment of patients with severe mental illness and comorbid substance misuse is discussed on p. 471).

Alcohol consumption in society

There is now general agreement that rates of alcohol dependence and alcohol-related disorders are correlated with the general level of alcohol consumption in a society. Previously it had been supposed that levels of intake among excessive drinkers were independent of the amounts taken by moderate drinkers. The French demographer Ledermann (1956) challenged this idea, proposing instead that the distribution of consumption within a homogeneous population follows a logarithmic normal curve. If this is the case, an increase in the average consumption must inevitably be accompanied by an increase in the number of people who drink an amount that is harmful.

Although the mathematical details of Ledermann’s work have been criticized, there are striking correlations between average annual alcohol consumption in a society and several indices of alcohol-related damage among its members. For this reason, it is now widely accepted that the proportion of a population that drinks excessively is largely determined by the average alcohol consumption of that population.

What then determines the average level of drinking within a nation? Economic, formal, and informal controls must be considered. The economic control is the price of alcohol. There is now ample evidence from the UK and other countries that the real price of alcohol (i.e. the price relative to average income) profoundly influences a nation’s drinking habits. Furthermore, heavy drinkers as well as moderate drinkers reduce their consumption when the tax on alcohol is increased.

The main formal controls are the licensing laws, but these do not seem to influence drinking behaviours in a consistent way when comparisons are made between different countries. Informal controls are the customs and moral beliefs in a society that determine who should drink, in what circumstances, at what time of day, and to what extent. Some communities appear to protect their members from alcohol misuse despite the general availability of alcohol. For example, alcohol-related problems are uncommon among Jews even in countries where there are high rates in the rest of the community. For a discussion of the economic and social aspects of alcohol consumption, see the Academy of Medical Sciences (2004).

Recognition of alcohol misuse

Detection

Only a small proportion of alcohol misusers in the community are known to specialized agencies. When special efforts are made to screen patients in medical and surgical wards, around 10–30% are found to misuse alcohol, with the rates being highest in Accident and Emergency wards. It has been estimated that of the one million people in England who are dependent on alcohol, only about 6% a year receive treatment. There are probably several reasons for this, including lack of help seeking by users, limited availability of specialist alcohol services, and under-identification of alcohol misuse by health professionals (National Institute for Health and Clinical Excellence, 2011a).

Screening questionnaires. Alcohol misuse often goes undetected because patients conceal the extent of their drinking. However, doctors and other professionals often do not ask the right questions. It should be a standard practice to ask all patients (medical, surgical, and psychiatric) about their alcohol consumption. Brief screening questionnaires can be helpful—for example, the CAGE questionnaire which consists of the following four questions.

• Have you ever felt you ought to Cut down on your drinking?

• Have people Annoyed you by criticizing your drinking?

• Have you ever felt Guilty about your drinking?

• Have you ever had a drink first thing in the morning (an ‘Eye-opener’) to steady your nerves or get rid of a hangover?

Two or more positive replies are said to identify alcohol misuse (see p. 125). Some patients will give false answers, but others find that these questions provide an opportunity to reveal their problems. Overall the CAGE has a good sensitivity but only modest specificity (Warner, 2004).

An alternative is the AUDIT, a 10-item structured interview designed at the request of the World Health Organization for screening for both currently harmful and potentially hazardous drinking. It shows good sensitivity and specificity, can identify mild dependence, and is probably the most useful screening questionnaire for clinicians and researchers in primary care (see Box 17.2).

Scores for each question range from 0 to 4, with the first response for each question scoring 0, and the last response scoring 4. For questions 9 and 10, which only have three responses, the scoring is 0, 2, and 4.

People who score in the range 8–15 should receive a brief intervention based on their risk for developing alcohol-related harm. Those who score 16–19 need a brief intervention and regular monitoring, including referral to specialist alcohol services if heavy drinking continues. Those who score in the range 20–40 should receive an early specialist referral and, depending on the severity of physical dependence, detoxification and other treatments (Room et al., 2005).

Box 17.2 AUDIT questionnaire: screen for alcohol misuse

1. How often do you have a drink containing alcohol?

• Never

• Monthly or less

• 2–4 times a month

• 2–3 times a week

• 4 or more times a week

2. How many standard drinks containing alcohol do you have on a typical day when drinking?

• 1 or 2

• 3 or 4

• 5 or 6

• 7 to 9

• 10 or more

3. How often do you have six or more drinks on one occasion?

• Never

• Less than monthly

• Monthly

• Weekly

• Daily or almost daily

4. During the past year, how often have you found that you were not able to stop drinking once you had started?

• Never

• Less than monthly

• Monthly

• Weekly

• Daily or almost daily

5. During the past year, how often have you failed to do what was normally expected of you because of drinking?

• Never

• Less than monthly

• Monthly

• Weekly

• Daily or almost daily

6. During the past year, how often have you needed a drink in the morning to get yourself going after a heavy drinking session?

• Never

• Less than monthly

• Monthly

• Weekly

• Daily or almost daily

7. During the past year, how often have you had a feeling of guilt or remorse after drinking?

• Never

• Less than monthly

• Monthly

• Weekly

• Daily or almost daily

8. During the past year, have you been unable to remember what happened the night before because you had been drinking?

• Never

• Less than monthly

• Monthly

• Weekly

• Daily or almost daily

9. Have you or someone else been injured as a result of your drinking?

• No

• Yes, but not in the past year

• Yes, during the past year

10. Has a relative or friend, doctor or other health worker been concerned about your drinking or suggested that you cut down?

• No

• Yes, but not in the past year

• Yes, during the past year

General ‘at-risk’associations. The next requirement is for the doctor to be suspicious about ‘at-risk’ associations. In general practice, alcohol misuse may come to light as a result of problems in the patient’s primary relationship and family, at work, with finances, or with the law. The alcohol misuser is likely to have many more days off work than the moderate drinker, and repeated absences on a Monday should arouse strong suspicion. The high-risk occupations (see p. 448) should also be borne in mind.

Medical ‘at-risk’ associations. In hospital practice, the alcohol-dependent patient may be noticed if they develop withdrawal symptoms after admission. Florid delirium tremens is obvious, but milder forms may be mistaken for an acute organic syndrome—for example, in pneumonia or post-operatively. In both general and hospital practice, at-risk factors include physical disorders that may be alcohol related. Common examples are gastritis, peptic ulcer, and liver disease, but others such as neuropathy and seizures should be borne in mind. Repeated accidents should also arouse suspicion.

Psychiatric at-risk associations include anxiety, depression, erratic moods, impaired concentration, memory lapses, and sexual dysfunction. Alcohol misuse should be considered in all cases of deliberate self-harm.

Drinking history

If any of the above factors raise suspicion of alcohol misuse, the next stage is to take a comprehensive drinking history (see Box 17.3). This should be done sensitively, with understanding that the patient may have difficulty in giving a clear history. The clinician should aim to build up a picture of what and how much the patient drinks throughout a typical day—for example, when and where they have the first drink of the day. The patient should be asked how they feel if they go without a drink for a day or two, and how they feel on waking. This can lead on to enquiries about the typical features of dependence and the range of physical, psychological, and social problems associated with it.

Box 17.3 Alcohol use history

• Describe a typical day’s drinking. What time is the first drink of the day?

• When did daily drinking start?

• Presence of withdrawal symptoms in the morning or after abstinence

• Previous attempts at treatment

• Medical complications

• Patient’s attitude towards drinking

To gain an idea of the duration of alcohol problems, key points in the history may include establishing when the patient first began drinking every day, when they began drinking in the mornings, and when, if ever, they first experienced withdrawal symptoms. It is useful to ask about periods of abstinence from alcohol, what factors helped to maintain this state of affairs, and what led to a resumption of drinking. This can lead on to enquiries about past attempts at treatment.

It is necessary to obtain a clear understanding of the patient’s own view of their drinking behaviour, because there are a number of possible treatment goals. In this situation the patient’s attitude to their problems plays a key role in deciding which approaches are likely to be most beneficial (see the section on motivational interviewing).

Laboratory tests

Several laboratory tests can be used to detect alcohol misuse, although none gives an unequivocal answer. This is because the more sensitive tests can give ‘false-positive’ results when there is disease of the liver, heart, kidneys, or blood, or if enzyme-inducing drugs such as anticonvulsants, steroids, or barbiturates have been taken. However, abnormal values point to the possibility of alcohol misuse. The most useful tests are listed in Box 17.4.

The treatment of alcohol misuse

Early detection and treatment

Early detection of excessive consumption of alcohol and alcohol misuse is important because treatment of established cases is difficult, particularly when dependence is present. Many cases can be detected early by general practitioners, physicians, and surgeons when patients are seeking treatment for another problem (see Box 17.5).

Brief intervention

General practitioners are well placed to provide early treatment of alcohol problems, and they are likely to know the patient and their family well. It is often effective if the general practitioner gives simple advice in a frank, matter-of-fact way, but with tact and understanding.

Brief intervention approaches generally involve simple education and advice about safe levels of alcohol consumption. The aim is to promote safer drinking, rather than abstinence. Generally, brief interventions lead to a significant reduction in alcohol consumption over the next few years, and are the best initial approach for a person whose alcohol consumption exceeds safe limits. It is generally agreed that brief interventions are not effective for people with severe drinking problems, particularly those who are alcohol dependent (Boland et al., 2008).

Box 17.4 Laboratory tests for alcohol dependence

Gamma-glutamyl-transpeptidase (GGT) Estimations of GGT in blood provide a useful screening test. The level is raised in about 70% of alcohol misusers, both men and women, whether or not there is demonstrable liver damage. The heavier the drinking, the greater is the rise in GGT.

Mean corpuscular volume (MCV) MCV is raised above the normal value in about 60% of alcohol misusers, and more commonly in women than in men. If other causes are excluded, a raised MCV is a strong indicator of excessive drinking. Moreover, it takes several weeks to return to normal after abstinence.

Carbohydrate-deficient transferrin This is a variant of a serum protein which transports iron, and levels are increased in response to heavy drinking. It is probably more specific than GGT.

Blood alcohol concentration A high concentration does not distinguish between an isolated episode of heavy drinking and chronic misuse. However, if a person is not intoxicated when the blood alcohol concentration is well above the legal limit for driving, they are likely to be unusually tolerant of alcohol. This tolerance suggests persistent heavy drinking. Alcohol is eliminated rather slowly from the blood and can be detected in appreciable amounts for 24 hours after an episode of heavy drinking. In clinical practice, breath alcohol is often used as a proxy measurement for blood alcohol.

Box 17.5 Approach to treatment of alcohol misuse

• Raise awareness of problem

• Increase motivation to change

• Support and advice

• Withdraw alcohol (or controlled drinking)

• High-intensity psychological treatments

• Alcoholics Anonymous

• Medication (disulfiram, acamprosate)

Motivational interviewing

Patients with problems of alcohol misuse, particularly those detected by screening methods, may be unsure whether or not to engage in treatment programmes. An appropriate interviewing style, particularly during the first assessment, can help to persuade the patient to engage in a useful review of their current pattern of drinking.

Confrontation is avoided in motivational interviewing, and a less directive approach is taken during which the patient is helped to assess the balance of the positive and negative effects of alcohol on their life. The clinician can help in this exercise by providing feedback to the patient about the personal risks that alcohol poses both to them and to their family, together with a number of options for change. The aim of motivational interviewing is to persuade the patient to argue their own case for changing their pattern of substance use (see Box 17.6).

For a review of motivational interviewing and its role in the treatment of substance misuse in general, see Treasure (2004).

Box 17.6 Motivational interviewing

• Express empathy.

• Avoid arguing; don’t be judgemental.

• Detect and ‘roll with’ resistance.

• Point out discrepancies in the patient’s history.

• Raise awareness about the contrast between the substance user’s aims and behaviour.

Treatment plans for more established alcohol misuse and dependence

For patients who have significant alcohol-related disorders, particularly alcohol dependence, treatment may need to be more intensive (Fig 17.2). Any intervention should be preceded by a full assessment, and should include a drinking history and an appraisal of current medical, psychological, and social problems. An intensive and searching enquiry often helps the patient to gain a new recognition and understanding of their problem, and this is the basis of treatment. As noted above, however, it is important to avoid confrontation, as this will only alienate someone who is likely to have very mixed feelings about the prospect of life without alcohol. It is usually desirable to involve the patient’s partner in the assessment, both to obtain additional information and to give the partner an opportunity to unburden their feelings.

Images

Figure 17.2 Relationship between extent of alcohol misuse and level of intervention required. Reproduced from A R Lingford-Hughes, S J C Davies, S McIver, T M Williams, M R C Daglish, and D J Nutt, Addiction: Imaging in clinical neuroscience, British Medical Bulletin, 65, © Oxford University Press, 2003, by permission of Oxford University Press.

A mutually agreed treatment plan should be worked out with the patient (and their partner if appropriate). There should be specific goals, and the patient should be required to take responsibility for realizing these. The goals should deal not only with the drinking problem, but also with any accompanying problems with regard to the patient’s health, marriage or other relationship, job, and social adjustment. In the early stages they should be short-term and achievable—for example, complete abstinence for 2 weeks. In this way the patient can be rewarded by early achievement.

Longer-term goals can be set as treatment progresses. These will be concerned with trying to change factors that precipitate or maintain excessive drinking, such as tensions in the family. When drawing up this treatment plan, an important decision is whether to aim for total abstinence or limited consumption of alcohol (controlled drinking).

Total abstinence versus controlled drinking

The disease model of alcoholism proposes that an alcohol-dependent person must become totally abstinent and remain so, as a single drink would lead to relapse. Alcoholics Anonymous have made this a tenet of their approach to treatment.

The issue of abstinence versus controlled drinking remains unresolved. A prevalent view is that controlled drinking may be a feasible goal for people whose alcohol misuse has been detected early, and who are not dependent or physically damaged. Abstinence is a better goal for dependent drinkers and others who have attempted controlled drinking unsuccessfully. If controlled drinking is to be attempted, the doctor should give the patient clear advice about safe levels (see p. 445).

Withdrawal from alcohol

For patients with the dependence syndrome, withdrawal from alcohol is an important stage in treatment which should be managed carefully. In the less severe cases, withdrawal may take place at home provided there is adequate support and clinical monitoring (see Table 17.7). This should involve daily assessment by the general practitioner, practice nurse, or specialist alcohol worker to check the patient’s physical state and supervise medication (see Box 17.7). In uncomplicated cases, withdrawal symptoms usually resolve within 4 to 6 days. However, any patient who is likely to have severe withdrawal symptoms, especially if there is a history of delirium tremens or seizures, should be admitted to hospital (Ritson, 2005). The Severity of Alcohol Dependence Questionnaire (SADQ) can be useful for estimating the likely severity of alcohol dependence and thereby gauging the amount of difficulty that the patient might encounter during withdrawal. An SADQ score of more than 30 is an indication for inpatient detoxification. Other indications for residential detoxification are very high alcohol consumption (over 30 units daily), concomitant benzodiazepine misuse, and significant medical or psychiatric comorbidity (National Institute for Health and Clinical Excellence, 2011a).

The extensive research on pharmacological treatment for alcohol withdrawal has been systematically reviewed by Lingford-Hughes et al. (2004). The most important concern is the prevention of major complications of withdrawal, such as seizures or delirium tremens. Treatment with benzodiazepines is usually the most suitable choice.

Table 17.7 Considerations before alcohol detoxification

1. What are the medical risks?

2. What setting is appropriate?

3. What does the patient want from detoxification?

4. What kind of aftercare is needed to help to maintain abstinence?

From Lingford-Hughes et al. (2004).

Benzodiazepines differ in their duration of action (see p. 517). Although the longer-acting compounds may carry the risk of over-sedation in the elderly or in those with significant liver disease, they also have the advantage of smoother withdrawal and generally better relief of withdrawal symptoms. Chlordiazepoxide is often used. A typical outpatient regimen would start with 20–30 mg four times daily, reducing and stopping over a period of 5–7 days. In more severe cases, particularly in inpatients, higher doses are commonly used. If convulsions occur, the dose of benzodiazepine should be reviewed and increased if necessary. Administration of a benzodiazepine that is well absorbed parenterally (e.g. lorazepam) may be useful to relieve severe acute withdrawal, although oral medication can usually be resumed promptly. In home-based withdrawal it is helpful for a family member or friend to supervise the medication.

Box 17.7 General management of alcohol detoxification

1. Explanation of the process to the patient and their family

2. The patient should stay off work and rest. They should not drive.

3. The patient should take plenty of fluids but avoid caffeinated drinks.

4. Daily visit by health professional.

5. Maintain abstinence.

6. Reducing course of benzodiazepines over 5–7 days (see text).

Carbamazepine has also been found to be effective in the treatment of alcohol withdrawal, and although not often used in the UK, it is a good alternative to the use of a benzodiazepine. There is no added benefit from using carbamazepine and a benzodiazepine together (Lingford-Hughes et al., 2004).

Clomethiazole was frequently used in the management of alcohol withdrawal in the past, but is no longer recommended, because of its toxicity when combined with alcohol and its danger in overdose. It is occasionally used for the most severe withdrawal states, where intensive inpatient medical monitoring is available, but there is no clear advantage compared with adequate doses of a benzodiazepine.

Antipsychotic drugs lower the seizure threshold and are less effective than benzodiazepines in preventing delirium. They are sometimes used to reduce agitation during alcohol withdrawal, but use of adequate doses of a benzodiazepine is a safer strategy. Antipsychotic drugs may be required occasionally, however, in patients with delusions that do not respond to benzodiazepines. In these circumstances, combination of antipsychotic treatment with benzodiazepines would be expected to attenuate the pro-convulsive effects of the antipsychotic drug.

Vitamin supplements, particularly thiamine, should also be given to prevent the Wernicke–Korsokov syndrome (see p. 320). Parenteral thiamine should be given to patients at high risk (i.e. those with alcohol dependence and a poor diet). In the treatment of delirium tremens or Wernicke’s encephalopathy, thiamine treatment should always precede glucose administration.

Psychological treatment

As noted above, provision of information and advice about the effects of excessive drinking is an important first stage in treatment. The information given should relate to the specific problems of the individual patient, including both those that have already occurred and those that are likely to develop if drinking continues. The technique of motivational interviewing can be useful (see p. 457).

More specialized, high-intensity psychological treatments are appropriate if the drinking problem is more serious, particularly in cases of alcohol dependence. Several treatment approaches have been employed, although there is significant overlap between the different therapies (see Box 17.8). Important features of successful psychological approaches include the use of behavioural techniques which require the drinker to take some action him- or herself, as well as the involvement of a partner and the drinker’s wider social network. There are also important roles for education and the improvement of social and interpersonal skills as these relate to alcohol misuse.

It may be helpful, for example, to identify situational or interpersonal triggers that cause the patient to drink excessively, and then to plan and rehearse new methods of coping with these situations. This is an important part of relapse prevention. The use of cue exposure to alcoholic drinks, without subsequent consumption, may also lessen the risk of subsequent relapse when the patient has to contend with the ready availability of alcohol in social settings. It is important for the patient to appreciate that a lapse in drinking behaviour does not have to progress to a full-blown relapse. Many patients who misuse alcohol have general deficiencies in problem-solving skills, and appropriate training may help to reduce relapse rates. If the patient is in a relatively stable relationship with a partner, cognitive–behavioural relationship therapy can produce improvements in both drinking behaviour and relationship adjustment.

For a review of psychological treatments for problem drinking, see Raistrick et al. (2006).

Pharmacological treatments to help to maintain abstinence

A number of different kinds of medication have been employed to help people to abstain from drinking or to experience less drinking-related harm. Medications are not regarded as ‘stand-alone’ treatments, and when used in the management of drinking problems should be combined with an appropriate psychosocial intervention (see Lingford-Hughes et al., 2004, and Box 17.9).

Box 17.8 High-intensity psychological therapies for alcohol-focused specialist treatment

Community reinforcement approach. A broad range of treatments, with the overall aim of changing the drinker’s social environment so that sobriety is rewarded. Components include training in communication skills, problem solving, and assertive drink refusal. Relationship therapy and promotion of relapse prevention are also offered. Disulfiram with monitored compliance is frequently used.

Social behaviour and network therapy. Use of the drinker’s social network to help to modify their drinking and maintain change. Facilitation of communication within the network and the agreement of common goals with the drinker. Use of pleasant social activities as an alternative to drinking.

Behavioural self-control training. Main use is to control drinking rather than to achieve abstinence. Can be used in groups, individually, or in a self-help format. Key components include setting drinking limits, development of methods to control drinking rate, drink refusal skills training, and self-reward for successful behaviours that replace drinking.

Coping and social skills training. Can be used in a group or individual format. Improves relationships by building up interpersonal skills, and uses cognitive emotional coping for mood regulation. Coping skills training enhances activities of daily living and facilitates dealing with stressful life events and the impact of alcohol-related cues that prompt drinking.

Cognitive–behavioural relationship therapy. Based on social learning theory. Uses behavioural contracting, communication skills training, and behavioural rehearsal with the drinker and their partner. Particularly appropriate in cases where the drinking problem and relationship difficulties exacerbate each other.

Cue exposure. Based on Pavlovian conditioning theory, and views craving for alcohol as a conditioned response to specific environmental cues. Aims to ‘extinguish’ conditioned responses and ameliorate craving by presenting relevant cues in the absence of the reinforcing effect of alcohol. Not used as a ‘stand-alone treatment.’

Relapse prevention. Difficult to define because it is a goal of treatment rather than a specific treatment modality. Based on cognitive–behavioural techniques, and involves training in social skills and coping and behavioural rehearsal. An important component of many other approaches.

See Raistrick et al. (2006).

Disulfiram (Antabuse) acts by blocking the oxidation of alcohol so that acetaldehyde accumulates. Some patients find it useful because the anticipation of an unpleasant reaction acts as a deterrent to impulsive drinking. The reaction includes facial flushing, throbbing headache, hypotension, palpitations, tachycardia, and nausea and vomiting. In vulnerable patients, cardiac arrhythmias and collapse may occur.

The main contraindications to the use of disulfiram are a history of heart failure, coronary artery disease, hypertension, psychosis, and pregnancy. The patient should be given clear verbal and written instructions together with a list of alcohol-containing substances to be avoided. Common side-effects are drowsiness, bad breath, nausea, and constipation. Disulfiram is given in a single dose of 800 mg on the first day of treatment, reducing over 5 days to 100–200 mg daily.

The efficacy of disulfiram depends on compliance. The treatment is likely to be more successful if a partner or health worker is able to supervise its use. However, the unsupervised use of disulfiram is not considered to be an effective approach (Rao and Luty, 2009).

Acamprosate (calcium acetyl homotaurinate) appears to suppress the urge to drink in response to learned cues, and can produce modest but useful reductions in drinking behaviour in alcohol-dependent individuals. It is believed to act by stimulating GABA-inhibitory neurotransmission and decreasing the excitatory effects of glutamate. The effects of acamprosate have not been consistent across studies. For example, a large trial in the USA (COMBINE) showed no increased benefit in measures of drinking behaviour when acamprosate was combined with cognitive–behaviour therapy, compared with cognitive–behaviour therapy alone (Anton et al., 2006). However, a meta-analysis of 19 randomized trials showed that over a 2-year follow-up, acamprosate significantly increased the abstinence rate, with a relative risk of 0.83 (95% CI, 0.77–0.88) (National Institute for Health and Clinical Excellence, 2011a).

Box 17.9 National Institute for Health and Clinical Excellence (NICE) guidance on the management of harmful drinking and alcohol dependence

1. For harmful drinking and mild dependence offer a high-intensity psychological treatment (see Box 17.8).

2. For those drinking over 15 units of alcohol a day and/or scoring 15–30 or more on the SADQ* test, offer community-based assisted withdrawal, or inpatient treatment if there are safety concerns.

3. After successful withdrawal for patients with moderate or severe alcohol dependence, consider offering acamprosate or oral naltrexone in combination with a high-intensity psychological treatment that promotes relapse prevention.

* Severity of Alcohol Dependence Questionnaire.

From National Institute for Health and Clinical Excellence (NICE) (2011a).

The usual dose of acamprosate is two tablets (333 mg each) three times daily with meals. In lighter patients (< 60 kg), four tablets daily are recommended. Acampro-sate is not metabolized in the liver and is excreted by the kidney. It is therefore unlikely to cause drug interactions. Adverse effects include diarrhoea and, less frequently, nausea, vomiting, and abdominal pain. Skin rashes may occur, as can fluctuations in libido.

The opioid antagonist, naltrexone, is believed to block some of the reinforcing effects of alcohol and in this way decrease the likelihood of relapse after detoxification. Not all trials have found a significant benefit over placebo. In the COMBINE study, the best effects on drinking behaviour were shown by participants who received both naltrexone and cognitive–behaviour therapy (Anton et al., 2006). A meta-analysis of 27 randomized trials showed that over a 12-month follow-up, naltrexone significantly increased rates of abstinence, with a relative risk of 0.83 (95% CI, 0.75–0.91), very similar to that of acamprosate (National Institute for Health and Clinical Excellence, 2011a). Common side-effects of naltrexone treatment include nausea, vomiting, headache, dizziness, and weight loss.

Topiramate is an anticonvulsant drug which has been shown to improve drinking outcomes in two randomized trials of 3 to 6 months in duration (Johnson, 2010). An effective dose appears to be about 100 mg a day. The adverse effects of topiramate include paraesthesia, anorexia, headache, abdominal pain, sleep disturbance, and cognitive impairment.

Antidepressant medication is useful in patients who experience persistent symptoms of major depression after detoxification. However, tricyclic antidepressants are not recommended because of potentially serious interactions, including cardiotoxicity and death following overdose. Some studies have suggested that selective serotonin reuptake inhibitors (SSRIs) such as citalopram can reduce drinking in non-depressed alcohol-dependent patients, but not all of the studies are in agreement. Re-analyses of some trials suggest that the effects of SSRIs may vary according to the ‘type 1’ and ‘type 2’ categories described by Cloninger (see p. 452). SSRIs may improve drinking outcome in type 1 alcohol dependence (later age of onset, anxious traits), but may worsen the outcome in type 2 alcohol dependence (early age of onset, positive family history, impulsive/antisocial personality traits) (Lingford-Hughes et al., 2004).

Other agencies concerned with drinking problems

Alcoholics Anonymous (AA) is a self-help organization founded in the USA by two alcoholic men, a surgeon and a stockbroker. It has since extended to most countries of the world. Members attend group meetings, usually twice weekly, on a long-term basis. In crisis they can obtain immediate help from other members by telephone. The organization works on the firm belief that abstinence must be complete. At present there are about 1200 groups in the UK.

Alcoholics Anonymous is based on a number of fundamental principles, known as the ‘Twelve Steps’, that members adhere to. It does not appeal to all problem drinkers because the meetings involve an emotional confession of problems, and because of the evangelical, quasi-religious nature of the twelve-step approach. However, the organization is of great value to some problem drinkers, and anyone with a drink problem should be encouraged to try it.

A treatment approach similar to that provided by Alcoholics Anonymous, coupled with encouragement to attend Alcoholics Anonymous meetings, was one of the psychological therapies employed in Project MATCH (see below). In general, all of the treatments that were employed appeared to be roughly equal in efficacy. However, patients with fewer psychiatric problems at entry tended have a better outcome with the Alcoholics Anonymous type of treatment.

Al-Anon is a parallel organization that provides support for the partners of excessive drinkers. Al-Ateen has a similar role for their teenage children.

Non-statutory agencies are voluntary bodies that provide a range of services, including advice for problem drinkers and their families, counselling, and help with occupational and social activities for those who have recovered.

Hostels are intended mainly for homeless problem drinkers. They provide rehabilitation and counselling. Usually abstinence is a condition of residence.

Results of treatment

In a controlled trial involving 100 male alcoholics, Edwards et al. (1977) compared simple advice with intensive treatment that included introductions to Alcoholics Anonymous, medication, repeated interviews, counselling for their wives, and, where appropriate, inpatient treatment as well. The advice group received a 3-hour assessment together with a single session of counselling with the partner present. The two groups were well matched. After 12 months there was no significant difference between them with regard to drinking behaviour, subjective ratings, or social adjustment.

Similar findings with regard to drinking behaviour were reported by Chick et al. (1988), who found that at a 2-year follow-up there was no difference in stable abstinence rates between patients who received a minimal treatment intervention, consisting mainly of advice, and those who were offered a broad range of therapies, including inpatient care and group therapy. However, the group that was offered the broad range of therapies suffered less alcohol-related harm, particularly in relation to family life.

Some have argued that abstinence rates by themselves do not provide a useful measure of treatment outcome. For example, although the patient may still be drinking, the amount consumed may decrease. This can be associated with a reduction in aspects of alcohol-related harm, as shown by the study by Chick et al. (1988). From this viewpoint, harm reduction, even where the individual continues to drink, is a worthwhile achievement. The principles of the harm-reduction approach have been applied to the misuse of other substances (see below).

Interest in the effectiveness of structured psychological treatments was studied by Project MATCH, a large randomized controlled trial of three psychological treatments for patients with alcohol problems (Project MATCH Research Group, 1997). The three treatments studied were a cognitive–behavioural intervention, a brief motivational enhancement therapy, and a treatment that aimed to help patients to make use of the ‘twelve-step’ philosophy of Alcoholics Anonymous. The main aim of the study was to attempt to find patient characteristics that predicted response to particular treatments. There were no important differences between the treatments, and few strong correlations were found between effectiveness and patient characteristics. However, in general the outcome was favourable, and the authors concluded that structured psychological treatments of various kinds were helpful in the management of alcohol misuse. In fact, the brief motivational enhancement therapy was generally as effective as the two more intensive psychological treatments.

Consistent with this, the UK Alcohol Treatment Trial (UKATT), which was conducted at several UK centres, found that motivational enhancement therapy was just as effective as social network therapy in decreasing alcohol consumption and alcohol dependence. However, at a 1-year follow-up the effects of treatment were fairly modest. For example, relative to baseline levels, average alcohol consumption on a drinking day fell from 27 units to 19 units, and the number of days on which patients abstained from alcohol rose from 30% to 45% (UK Alcohol Treatment Trial Research Team, 2005).

There are likely to be factors within the patient that will predict a good response to a number of different kinds of treatment. There is some disagreement as to what these factors are, but the following generally predict a better prognosis regardless of which treatment is used:

• good insight into the nature of the problems

• social stability in the form of a fixed abode, family support, and ability to keep a job

• ability to control impulsiveness, to defer gratification, and to form satisfactory emotional relationships.

For reviews of the effectiveness of a broad range of treatment approaches for alcohol use disorders, see Rao and Luty (2009) and the National Institute for Health and Clinical Excellence (2011a).

Prevention of alcohol misuse and dependence

In seeking to prevent excessive drinking and alcohol-related disorders, two approaches are possible. The first is to improve the help and guidance available to the individual, as already described. The second is to introduce social changes that are likely to affect drinking patterns in the population as a whole (see Box 17.10). It is this second group that we are concerned with here. Consumption within a population might be reduced by four methods:

1The pricing of alcoholic beverages. Putting up the price of alcohol would probably reduce consumption within the population. Based on a systematic review, Wagenaar et al. (2010) predicted that doubling alcohol taxes in the USA would reduce direct alcohol-related mortality by 35%, traffic fatalities by 11%, and violent crime by 2%.

2Controls on advertising. Controlling or abolishing the advertising of alcoholic drinks might be another preventive measure. It is unclear how far advertising encourages the use of particular brands of alcohol rather than overall consumption. However, in the UK, annual expenditure on alcohol advertising rose from £150 million to £250 million between 1989 and 2000, and during that time there was a strong correlation between advertising expenditure and mean weekly alcohol consumption by children aged 11–15 years (Academy of Medical Sciences, 2004).

3Controls on sale. Another preventive measure might be to control sales of alcohol by limiting hours or banning sales in supermarkets. Although relaxation of restrictions has been shown to lead to increased sales of alcohol in some countries, it does not follow that increased restrictions would reduce established rates of drinking. However, there is evidence that a higher minimum age for legal drinking is associated with a decrease in alcohol consumption and fatal car accidents in young drivers (McCartt et al., 2010). There is growing concern about the heavy drinking associated with nightlife culture in many UK cities.

4Health education. It is not known whether education about alcohol misuse is effective. Little is known about how attitudes are formed or changed. Although education about alcohol would seem to be desirable, it cannot be assumed that classroom lectures or mass media propaganda would alter attitudes. In general, there is little convincing evidence that such approaches are effective (Room et al., 2005).

Box 17.10 Some recommendations by the Academy of Medical Sciences (2004) for decreasing alcohol-related harm in the UK

• Increase taxes on alcohol to restore its affordability relative to income to that obtaining in the early 1970s.

• Reduce the duty-free allowance of alcohol for travellers.

• Review advertising and promotion of alcoholic drinks, particularly to young people.

• Improve medical research on the damaging effects of alcohol.

• Inform the public and encourage debate about the extent of alcohol-related harm (see Box 17.1).

• Reduce the statutory blood alcohol concentration for drivers from 80 mg/100 ml to 50 mg/100 ml. Impose a zero statutory blood alcohol level for young drivers up to the age of 21 years.

Other substance use disorders

Under this heading we shall consider the use and misuse of substances other than alcohol. Although these substances include agents such as volatile substances (inhalants), the general term drug will be employed because it is in common use. In this discussion the term misuse will be applied to what is classified as harmful use in ICD-10 and abuse in DSM-IV (see Table 17.3).

Epidemiology

Illicit drug use

The 2009 National Survey on Drug Use and Health in the USA found that 8.7% of the population aged 12 years or over had used an illicit substance in the past month (Substance Abuse and Mental Health Services Administration, 2010). Use was highest in unemployed people in the 16–25 years age range. The most commonly used illicit drug was cannabis, with a slight majority of illicit drug takers (58%) using cannabis only. The Psychiatric Morbidity Survey reported that, in England, 9.2% of adults had taken an illicit drug in the last year, most commonly cannabis (7.5%) (McManus et al., 2007). Use was higher in men (12.0%) than in women (6.7%). Among males, drug use was highest in black men (21.8%) and lowest in South Asian men (3.5%). In women the highest rate of drug use was in white women (6.8%), with South Asian women reporting the lowest rate (0.8%). Highest rates of drug use in the last year were seen in men aged 25–34 years (28.9%) and women aged 16–24 years (21.9%). About 4% of the UK population had used at least one Class A drug (opiate, cocaine, lysergic acid diethylamide, or injected stimulant) in the previous year (see Table 17.8).

The European School Survey Project on Alcohol and Other Drugs (2007) surveyed drug use in 15- to 16-year-olds in 37 European countries. On average, 23% of boys and 17% of girls had tried illicit drugs at least once in their lifetime. Again cannabis was by far the most commonly used drug. The country with the most frequent cannabis use was the Czech Republic (45%), and that with the lowest use was Armenia (3%). The UK had the third highest rate (29%). However, there was a 14% decrease in illicit drug use in the UK between 1995 and 2007.

Drug misuse and dependence

Little is known for certain about the prevalence of different types of drug misuse and drug dependence. In the UK, information comes from three main sources—criminal statistics (mainly based on offences involving the use and misuse of illicit drugs), special surveys, and hospital admissions.

The Psychiatric Morbidity Survey reported that in England the prevalence of drug dependence during the previous 12 months was 4.1% (5.4% of men and 2.3% of women). Most of the dependence was on cannabis (3.4%). The highest frequency was in the 16–24 years age group (McManus et al., 2007). These rates are similar to those found in 2000. Rates of drug dependence are much higher among the homeless population and those in prison. For example, the British Psychiatric Morbidity Survey found that 24% of people who were sleeping rough met the criteria for drug dependence. Among remand prisoners, 51% of men and 54% of women reported dependence on drugs before coming into prison, whereas among sentenced prisoners, 43% of men and 41% of women reported drug dependence (Gill et al., 1996; Singleton et al., 1997).

Table 17.8 Illicit drug use in England in the past year

Cannabis 7.5%

Cocaine 2.5%

Ecstasy 1.2%

Amphetamines 0.7%

Amyl nitrite 0.7%

Tranquillizers 0.7%

Magic mushrooms 0.6%

Heroin and methadone 0.3%

LSD 0.2%

Crack 0.2%

Anabolic steroids 0.1%

Volatile substances 0.1%

From McManus et al. (2007).

The National Comorbidity Survey Replication in the USA (Kessler et al., 2005b) found rather lower 12-month rates of drug dependence (0.4%), and the rate of drug abuse was 1.4%. It is difficult to know whether the differences between the UK and the USA in reported rates of drug dependence are real variations in incidence or might instead reflect differences in how the presence of drug dependence is assessed.

Rates of drug misuse and dependence are higher in disadvantaged areas of large cities. Adolescents are at risk, particularly around school-leaving age. A high proportion of attenders at drug-dependence clinics in large cities are unemployed, with few stable relationships, and leading disorganized lives. However, many young drug users remain in employment and apparently regard their drug taking as part of normal recreational activity for their particular peer group.

Causes of drug misuse

There is no single cause of drug misuse. It is generally argued that four factors are important:

• availability of drugs

• a vulnerable personality

• an adverse social environment

• pharmacological factors.

The widespread availability of illicit drugs means that occasional use in a young person can no longer be regarded as abnormal behaviour. However, about 10% of those who experiment with drugs will go on to develop problems with them (Robson, 2009). Once drug taking has started, personal, social, and pharmacological factors play a role in determining misuse and dependence. Studies of the aetiology of misuse of substances other than alcohol are still at an early stage. For example, it is unclear whether similar risk factors predict misuse of a range of substances, including alcohol, or whether there is some specificity in the mechanisms, which leads certain individuals to misuse particular substances.

Availability of drugs

Drugs involved in misuse can be obtained in three main ways:

1legally without prescription—nicotine and alcohol are obvious contemporary examples, and in the nineteenth century much dependence on opioids resulted from taking freely available remedies containing morphia

2by prescription from doctors—in the first part of the twentieth century much of the known dependence on opioids and barbiturates in Western countries was due to drugs obtained from this source; more recently, benzodiazepine dependence was often acquired in this way

3from illicit sources (‘street drugs’).

Personal factors

Of those who experiment with drugs, the users who go on to develop problems appear to have some degree of personal vulnerability before they begin taking drugs. They may live in disrupted families and have started taking drugs at a relatively young age. Associated behaviours include a poor school record, truancy, or delinquency. Traits such as sensation seeking and impulsivity are also common. Many of those who misuse drugs report depression and anxiety, but it is seldom clear whether these are the causes or the consequences of drug misuse and dependence. Some give a history of mental illness or personality disorder in the family. Genetic factors are strongly implicated in a variety of drug use disorders, but less so in drug use itself. This suggests that drug use in general is largely dependent on factors such as availability and social environment, but that genes contribute to the propensity to develop harmful use and dependence (Schulden et al., 2009; Bienvenu et al., 2011).

Social environment

The risk of drug misuse is greater in societies that condone drug use of one kind or another. Within the immediate group, there may be social pressures for a young person to take drugs to achieve status. Thus drug use by individuals is influenced by substance use by their peers or parents. There are also links between drug misuse and indices of social deprivation, such as unemployment and homelessness (Gill et al., 1996).

Neurobiology of drug use, misuse, and dependence

Use, misuse, and dependence. Many individuals use drugs without misusing them, and not all drug misusers become drug dependent. Therefore it is useful to study the biological mechanisms underlying drug use, misuse, and dependence separately. Drugs are used and misused because they have the ability to serve as positive reinforcers—that is, they increase the frequency of behaviours that lead to their use (Everitt and Robbins, 2005). Drugs act as positive reinforcers because they cause positive subjective experiences such as euphoria or a reduction in anxiety.

Neurobiological mechanisms. An important neurological substrate that mediates such effects is the midbrain dopamine system, the cell bodies of which originate in the ventral tegmental area and innervate the forebrain, particularly the ventral striatum. It has been proposed that these dopamine pathways form part of a physiological reward system, which has the property of increasing the frequency of behaviours that activate it. Therefore it is of interest that administration of different kinds of drugs of misuse—including alcohol, nicotine, and opioids—to animals increases dopamine release in the nucleus accumbens. This suggests that activation of midbrain dopamine pathways may be a common property of drugs that have a propensity to be used and misused (Everitt and Robbins, 2005).

Although this hypothesis may explain in part the social use of particular drugs, it does not account for the misuse of drugs in some circumstances. Presumably this is a consequence of interactions between the pharmacological properties of the drug, the biological disposition and personality of the user, and the social environment. Current neurobiological formulations of drug dependence suggest that the switch from controlled drug taking to compulsive use is associated with a lessening of prefrontal ‘reflective’ processes and a corresponding increase in striatal activity which underpins more habitual behaviours. These changes might explain the ability of repeated drug administration in some people to ‘hijack’ executive behaviour almost exclusively to serve the needs of the drug habit, and the poor judgement and decision making shown by people with substance dependence (Everitt et al., 2008).

Physiological and non-physiological dependence. Dependence on drugs has traditionally been described as either psychological or physiological. In DSM-IV, dependence is categorized according to whether or not it is physiological in nature. Physiological dependence is diagnosed when a substance user demonstrates either tolerance of the pharmacological effects of the drug or a characteristic withdrawal syndrome when use of the drug is reduced. Cardinal features of both physiological and non-physiological dependence are desire for the drug and drug-seeking behaviour. These features probably result from the continued need to obtain the reinforcing properties of the drug, as described above. Learning and conditioning factors are likely to be important in this context (Everitt and Robbins, 2005).

It is important to note that, even in non-physiological dependence, phenomena such as craving and dysphoria are associated with altered brain function. For example, in experimental studies the discontinuation of cocaine after a period of administration results in a sharp decline in dopamine release in the nucleus accumbens. It is possible that such an effect could correspond clinically to symptoms such as anhedonia and a desire to obtain more supplies of the drug.

Neurobiology of tolerance and dependence. The phenomena of tolerance and withdrawal are believed to be a result of neuroadaptive changes in the brain. These are part of a homeostatic process which counteracts the acute pharmacological effects that occur when a drug is administered. For example, many drugs that are misused for their anxiolytic and hypnotic properties (e.g. barbiturates, benzodiazepines, and alcohol) have, among their acute pharmacological effects, the ability to enhance brain GABA function. During continued treatment with these agents, adaptive changes occur in GABA- and benzodiazepine-receptor sensitivity that tend to offset the effect of the drugs to facilitate GABA neurotransmission. Such an effect could account for the phenomenon of tolerance, with the result that an individual needs to take more of the drug in order to produce the same pharmacological effect.

If the drug is abruptly discontinued, persistence of the adaptive changes in receptor function could lead to a sudden decline in GABA activity. In fact many of the clinical features of withdrawal from anxiolytic drugs, such as anxiety, insomnia, and seizures, can be explained on the basis of diminished brain GABA function. Such an effect can also explain the well-known phenomenon of cross-tolerance between anxiolytics and hypnotics and alcohol, which makes it possible, for example, to treat alcohol withdrawal with a benzodiazepine.

Similar kinds of adaptive changes have been proposed to account for the tolerance and withdrawal phenomena that are seen with other drugs of misuse. For example, while acute administration of opioids decreases the firing of noradrenaline cell bodies in the brainstem, tolerance of this effect occurs during repeated treatment, probably because of adaptive changes in the sensitivity of opioid receptors. If opioids are now abruptly withdrawn, there is a sudden increase in the firing of noradrenaline neurons and in the release of noradrenaline in terminal regions. Increased noradrenergic activity may account for several of the clinical features of acute opioid withdrawal, including sweating, tachycardia, hypertension, and anxiety. These studies have led to the use of the noradrenaline autoreceptor agonists, clonidine and lofexidine, in the management of opioid withdrawal (Lingford-Hughes et al., 2010).

Although the positive reinforcing actions of drugs are considered to be the major factor in promoting continued drug use, withdrawal effects are also likely to play a part, because they are invariably unpleasant, and individuals are likely to try to prevent them by taking more of the drug. It is worth noting that for many months following the cessation of a clear-cut withdrawal syndrome, dependent individuals may experience a sudden intense desire to consume the drug. Often particular psychological and social stimuli that were previously associated with drug use may trigger intense craving associated with symptoms resembling a withdrawal state. It has been proposed that a single exposure to the drug during this period may rapidly lead to a full relapse to drug dependence—the so-called reinstatement effect. An analogous effect has been shown in previously drug-dependent animals, where a single priming dose of the drug concerned can lead to a full recovery of drug-seeking behaviours that had previously been extinguished.

For a review of the brain mechanisms involved in drug misuse and their implications for treatment, see Ling-ford-Hughes et al. (2010).

Adverse effects of drug misuse

Drug misuse has many undesirable effects, both for the individual and for society.

Physical health

Drug misuse can lead people to neglect their health, in addition to the direct physical consequences of the substance itself. These are discussed in more detail under the heading of individual drugs.

Intravenous drug use poses particular health risks. This practice is very common with opioid use, but barbiturates, benzodiazepines, amphetamines, and other drugs may be taken in this way. Intravenous drug use has important consequences, which include both local and general effects (see Table 17.9).

The most serious complications of intravenous drug use include HIV infection and hepatitis. Rates of HIV infection among drug users in the UK are lower than those found in some other European countries, and some attribute this to the vigorous harm reduction policies in the UK (methadone prescribing, needle exchanges, and education for drug users). However, hepatitis C is a major concern, as preliminary studies suggest that this infection has a prevalence of 50–80% among UK users who inject drugs. Rates of hepatitis B are lower but still significant (30–50%). Accidental drug overdose can occur by any route, but there is a far higher risk of death from heroin overdose when the intravenous route is used.

Table 17.9 Some consequences of intravenous drug misuse

Local

Vein thrombosis

Infection of injection site

Damage to arteries

Systemic

Bacterial endocarditis

Hepatitis B and C

HIV infection

Accidental overdose

Substance dependence in women

Substance misuse treatment services, including those for alcohol-related disorders, are not usually designed to meet the special needs of women, because existing treatment models have been developed for men. Clinicians need to take into account factors such as the following:

• social and parenting responsibilities

• possible history of victimization and sexual abuse

• social barriers to obtaining medical care

• the availability of female therapists.

Drug misuse in pregnancy and the puerperium

Often drug misusers do not take up healthcare services until late into the pregnancy, which increases the health risk to both mother and baby. When a pregnant woman misuses drugs, the fetus may be affected. When drugs are taken in early pregnancy, there is a risk of increased rates of fetal abnormality. Opioids may directly decrease fetal growth. When drugs are taken in late pregnancy, the fetus may become dependent on them. The risk of fetal dependence is high with heroin and related drugs, and after delivery the neonate may develop serious withdrawal effects that require skilled care. If the mother continues to take drugs after delivery, the infant may be neglected. Intravenous drug use may lead to infection of the mother with HIV or other conditions that can affect the fetus. Engagement in treatment and good antenatal care reduce the risks to both mother and baby.

For a review of problem drug use in women, see Greenfield et al. (2010).

Psychiatric comorbidity

There is a strong association between substance misuse and psychiatric comorbidity (often described as dual diagnosis). For example, people with substance misuse often have additional diagnoses of personality disorder, depression, and anxiety. Sometimes symptoms of mood disturbance may be a direct result of drug use. For example, people who use stimulants can experience depression subsequently, particularly during periods of acute withdrawal.

In other cases the relationship is more complex, with premorbid psychiatric disorder interacting with substance misuse. Thus patients with primary psychiatric disorders such as schizophrenia, bipolar disorder, and sociopathic personality disorder frequently misuse alcohol and illicit drugs. This practice increases the morbidity of the underlying disorder and heightens the risk of violence and self-harm. There is debate about the best ways of delivering treatment services to such patients, but as yet there is little firm evidence to provide guidance. The general consensus is that an integrated service, where the same clinical team deals with both psychiatric and substance misuse disorders, is likely to be the best approach. However, implementing such a service model poses challenges (see p. 471).

Social consequences of drug misuse

There are three reasons why drug misuse can lead to undesirable social effects.

1. Chronic intoxication may affect behaviour adversely, leading to unemployment, motoring offences, accidents, and family problems, including neglect of children.

2. Illicit drugs are generally expensive, so the user may steal or sell sexual favours in order to obtain money.

3. Drug misusers often keep company with one another, and those with previously stable social behaviour may be under pressure to conform to a group ethos of antisocial or criminal activity.

The economic costs of problem drug use in the UK have been estimated by Godfrey et al. (2002) to be between £10.1 and £17.4 billion annually (see Box 17.11).

Diagnosis of drug misuse

It is important to diagnose drug misuse early, at a stage when dependence may be less established and behaviour patterns less fixed, and the complications of intravenous use may not have developed. Before describing the clinical presentations of the different types of drugs, some general principles will be given. The clinician who is not used to treating people who misuse drugs should remember that they are in the unusual position of trying to help a patient who may be attempting to deceive them. Patients who are misusing heroin may overstate the daily dose in order to obtain extra supplies for their own use or for sale to others. Furthermore, many patients take more than one drug but may not say so. It is important to try to corroborate the patient’s account of the amount that they are taking by asking detailed questions about the duration of drug taking, and the cost and source of drugs, by checking the story for internal consistency, and by external verification whenever possible.

Box 17.11 Social costs of drug misuse in the UK

Users: premature death, physical and mental illness, low educational achievement, unemployment

Families: adverse effect on children, poverty and deprivation

Others: victims of dangerous driving, victims of crime, victims of assault

Community: criminal activity related to drug dealing, environmental impoverishment, health and crime risks to community

Industry: sickness absence, theft in the workplace, productivity losses, costs of security

Public sector: healthcare expenditure, criminal justice expenditure, social services care and benefits

Physical signs

Certain physical signs lead to the suspicion that drugs are being injected. These include needle tracks and thrombosis of veins, especially in the antecubital fossa, wearing garments with long sleeves in hot weather, and scars. Intravenous drug use should be considered in any patient who presents with subcutaneous abscesses or hepatitis.

Behavioural signs

Behavioural changes may also suggest drug misuse. These include absence from school or work, and occupational decline. Dependent people may also neglect their appearance, isolate themselves from former friends, and adopt new friends in a drug culture. Minor criminal offences, such as petty theft and prostitution, may also be indicators.

Medical presentation

Dependent people may come to medical attention in several ways. Some declare that they are dependent on drugs. Others conceal their dependency, and ask for controlled drugs for the relief of pain such as renal colic or dysmenorrhoea. It is important to be particularly wary of such requests from temporary patients. Others present with drug-related complications, such as cellulitis, pneumonia, hepatitis, or accidents, or for the treatment of acute drug effects, overdose, withdrawal symptoms, or adverse reactions to hallucinogenic drugs. A few are detected during an admission to hospital for an unrelated illness.

Taking a drug history

When taking a drug history (see Box 17.12) from a patient who is misusing drugs, the doctor should ask the patient to describe their drug use the previous day and also to describe a typical drug-using day(which drug, how often, and which route of use). A typical week can be described if drugs are not used every day. The doctor should ask about craving, withdrawal symptoms, and other features of the dependence syndrome, such as increased tolerance of the drug and the priority of drug seeking over other duties and pleasures. The patient should be asked specifically about risky behaviour, such as dangerous injecting (into the groin or neck or infected injection sites), and sharing injection equipment.

chronological history of the development of use of each drug can then be taken. Useful milestones can include the first use of the drug, when the patient began to use the drug daily, when withdrawal symptoms were first experienced, and when the patient first injected drugs. A history of sharing injection equipment will be important when estimating the risk of HIV or hepatitis.

Box 17.12 Drug-using history

• Typical drug-using day or week

• Types and quantities of drugs taken (including alcohol and nicotine)

• Symptoms experienced when drugs are unavailable

• Tolerance and primacy of drug habit

• Risky behaviour

• Developmental history of drug misuse

• Abstinence and relapse triggers

• Medical and social complications

• Psychiatric and forensic history

If the patient has had periods of abstinence, it is useful to ask which influences helped them to achieve this and what factors led to relapse. A history of complications should include adverse effects of the drug itself as well as complications of the route of administration. Any history of accidental overdose should also be elicited. The patient should be asked about family, occupational, and legal problems. Any past history of treatment should be elicited. There are several possible goals in the treatment of drug misusers. Abstinence is one, but safer drug use (harm reduction) may be a more realistic aim for many. It is therefore important to obtain the patient’s views about their drug use and the changes that they would like to make.

Laboratory diagnosis

Whenever possible, the diagnosis of drug misuse should be confirmed by laboratory tests. Urine testing is most commonly used, as it is easier and less invasive than repeated blood testing. However, saliva, blood, and hair analysis can be useful in certain circumstances. The laboratory should be provided with as complete a list as possible of drugs that are likely to have been taken, including those that have been prescribed.

For a review of laboratory investigations, see Abraham and Luty (2010).

Prevention, treatment, and rehabilitation: general principles

Prevention

Because treatment is difficult, considerable effort should be given to prevention. For many drugs, important preventive measures such as restricting availability and lessening social deprivation depend on government, not medical, policy. However, the reduction of over-prescribing by doctors is important, especially with regard to benzodiazepines and other anxiolytic drugs and opiates.

Although education programmes by themselves do not seem to be effective in prevention, it is important that information about the dangers of drug misuse should be available to young people in the school curriculum and through the media. Another aspect of prevention is the identification and treatment of family problems that may contribute to drug taking. In all of these preventive measures the general practitioner has an important role. Some young people are particularly vulnerable to drug misuse. This includes those who have been in care, those who are homeless, and those who are not in school due to either truancy or exclusion. Identification of young people at risk of drug misuse should be followed by specific psychosocial interventions that are designed to divert them away from drug use (National Institute for Health and Clinical Excellence, 2007a).

Treatment

Motivation and change

When drug misuse has already begun, treatment is more effective if it is given before dependence is established. At this stage, as at later stages, the essential step is to motivate the patient to control their drug taking. This requires a combination of advice about the likely effects of continuing misuse, and help with any concurrent psychological or social problems. The techniques of motivational interviewing (Treasure, 2004) (see p. 457 and Box 17.6) may be useful here. The stages of change model described by Prochaska and DiClemente (1986) can help the clinician to encourage motivation effectively (see Box 17.13).

Box 17.13 Stages of change model

Pre-contemplation

Misuser does not believe that there is a problem, although others recognize it.

Contemplation

Individual weighs up the pros and cons and considers that change might be necessary.

Decision

The point is reached where a decision is made to act (or not to act) on the issue of substance misuse.

Action

Individual chooses a strategy for change and pursues it.

Maintenance

Gains are maintained and consolidated. Failure may lead to relapse.

Relapse

Return to previous pattern of behaviour.

However, relapse may be a positive learning experience, with lessons for the future.

Aims of treatment

The ultimate aim of treatment of the drug-dependent patient is a good personal and social adjustment in the absence of drug use. However, drug withdrawal (or detoxification) by itself has no effect on long-term outcome (Vaillant, 1988), so this process should be part of a wider treatment programme. If withdrawal cannot be achieved, continued prescribing of certain drugs (e.g. opioids) may be considered as part of a harm reduction programme (see below). In addition, psychological treatment and social support are required. The general principles of treatment will be outlined below, and later sections of the chapter will consider treatment specific to individual drugs.

Treatment setting

In the UK, drug misusers are treated in a number of different settings, and there is increasing variation in the way that care is delivered locally. A model of shared care in which drug misusers are managed jointly by the GP and specialist services is being replaced by a system with a wider range of care providers. For example, treatment can be given by the GP supported by a nurse or drugs worker from the voluntary sector. In secondary care and in specialized drug treatment services, patients continue to be managed by a multidisciplinary team using the key worker system. Inpatient care is provided in psychiatric hospitals, in psychiatric units in general hospitals, or in a small number of specialist inpatient units. Individual counselling, group therapy, and therapeutic communities are provided by a variety of charitable organizations. All doctors in the UK who are treating drug misusers for their drug problems should provide information on the standard form to their local Regional Drug Misuse Database. Contact numbers for this can be found in the British National Formulary.

Physical complications

The complications of self-injection may require treatment in a general hospital. They include accidental overdose, skin infections, abscesses, septicaemia, hepatitis, and HIV infection. Drug misusers will also need help with general health problems such as nutrition and dental care. Immunization against hepatitis B may be advisable.

Principles of withdrawal

The withdrawal of misused drugs is sometimes called detoxification. For many drugs, particularly opioids, withdrawal may sometimes be most effectively undertaken in hospital (see below). Withdrawal from stimulant drugs and benzodiazepines can often be an outpatient procedure, provided that the doses are not very large and that barbiturates are not taken as well. Nevertheless, the risk of depression and suicide should be borne in mind.

Drug maintenance

Some clinicians undertake to prescribe certain drugs to dependent people who are not willing to give them up. The usual procedure is to prescribe a drug which has a slower action (and is therefore less addictive) than the ‘street’ drug. For example, methadone is prescribed in place of heroin. When this procedure is combined with help with social problems and a continuing effort to encourage the person to accept withdrawal, it is called maintenance therapy.

The rationale of this approach is twofold.

1. Prolonged prescribing will remove the need for the patient to obtain ‘street’ drugs, and will thereby reduce the associated physical and social damage.

2. Social and psychological help, aided by the natural process of maturing, will give the patient the confidence and skills to be able to give up drugs eventually.

Maintenance drug treatment is used in particular for patients with opioid dependence. If maintenance drug therapy is used, it should be remembered that some drug-dependent people convert tablets or capsules into material for injection, which is a particularly dangerous practice. Furthermore, some attend a succession of general practitioners in search of supplementary supplies of drugs. They may withhold information about attendance at clinics or pose as temporary residents.

Some patients who receive maintenance drugs achieve a degree of social stability, but others continue heavy drug misuse and deteriorate both medically and socially. Patients who are on maintenance methadone are more likely to be retained in treatment than those in drug-free programmes. This may be important because the length of time spent in treatment, regardless of type, is the best predictor of favourable outcome. (The use of methadone maintenance treatment in the management of opioid dependence is considered in more detail below.)

Harm reduction

The increase in HIV and hepatitis C infection has emphasized the importance of harm reduction programmes, of which prescribing maintenance may be one component. The purpose of such programmes is to increase the number of substance misusers who enter and comply with treatment. The aim is to identify intermediate treatment goals which, although not involving total abstinence, nevertheless reduce the risk of drug misuse to the individual and society. For example, even if a patient continues to misuse drugs, the risk of hepatitis and HIV infection can be reduced by providing appropriate education and practical help. Such interventions may result in the drug misuser using safer routes of drug administration or sterile injection equipment. Counselling and screening for hepatitis and HIV may also be worthwhile, and hepatitis B vaccination should be offered to non-immune patients.

Psychosocial treatments

Treatment for drug misuse should always include psychosocial approaches. The usual way to deliver this is through a key worker who institutes measures such as counselling, education, and motivational interviewing. Practical help with benefits and information about services can also be provided. All patients should be aware of self-help and mutual aid groups such as Narcotics Anonymous, which can be of great benefit to many individuals. Some patients are helped by treatment in a therapeutic community in which there can be frank discussion of the effects of drug taking on the person’s character and relationships within the supportive setting of the group (for an outline of community therapy, see p. 595).

More formal psychological treatments as described for the management of alcohol misuse (see p. 460) can also be helpful, and have been reviewed by the National Institute for Health and Clinical Excellence (2007b). The aim of such treatment is to increase recreational and personal skills so that the patient becomes less reliant on drugs and the drug culture as a source of satisfaction. Involvement of the patient’s partner and family in structured couple and family therapy is often helpful.

As with alcohol dependence, cognitive–behavioural techniques can be used to identify, in advance, situations that act as triggers for drug use. In this way alternative methods of coping can be planned (relapse prevention). It has already been mentioned that when a drug misuser is confronted with a situation that contains personal cues for drug use, they can experience acute discomfort associated with a strong desire to use the drug. The technique of cue exposure aims, through repeated exposure, to desensitize the drug misuser to these effects and thus improve their ability to remain abstinent. Although contingency management is not currently widely used in the UK, there is good evidence for its effectiveness in reducing drug misuse. Contingency management provides a variety of incentives in the form of vouchers, privileges, or modest financial rewards to encourage individuals to modify their drug misuse and increase health-promoting behaviours (Department of Health, 2007b; National Institute for Health and Clinical Excellence, 2007b).

Rehabilitation

Many drug takers have difficulty in establishing themselves in normal society. The aim of rehabilitation is to enable the drug-dependent person to leave the drug subculture and to develop new social contacts. Unless this can be achieved, any treatment is likely to fail.

Rehabilitation may be undertaken after treatment in a therapeutic community (see p. 595). Patients first engage in work and social activities in sheltered surroundings, and then take greater responsibility for themselves in conditions that are increasingly similar to those of everyday life. Hostel accommodation is a useful stage in this gradual process. Continuing social support is usually required when the person makes the transition to normal work and living.

Dual-diagnosis patients

As noted above, the management of patients with both substance misuse and serious psychiatric illness, such as schizophrenia or mood disorders, poses several additional challenges. Such comorbidity is associated with an increased risk of violence and suicide and poorer clinical and social outcomes (Department of Health, 2007b; National Institute for Health and Clinical Excellence, 2011b). Patients with dual diagnoses are particularly difficult to retain in treatment, and frequently present in crisis with many unmet social needs. Drake et al. (2007) identified the following components of a successful integrated treatment service for patients with substance misuse and serious psychiatric illness:

• appropriate staff training

• use of a recovery-based approach with expectation of recovery in the longer term

• multidisciplinary case management with assertive outreach to engage and retain patients in treatment

• some form of peer-orientated group intervention led by a professional facilitator

• emphasis on motivational interviewing, harm reduction, and skills training

• long-term community support, including day care and residential care

• pharmacotherapy (e.g. naltrexone and disulfuram), with particular consideration of clozapine for those with schizophrenia and substance misuse.

It is worth emphasizing that in many settings the cooccurrence of serious mental illness and drug and alcohol misuse is the norm rather than the exception. Recent guidance from the National Institute for Health and Clinical Excellence highlights the importance of recognizing patients with comorbid psychosis and substance misuse, and the development of suitably integrated services to tackle both problems (National Institute for Health and Clinical Excellence, 2011b).

Misuse of specific types of drug

Opioids

This group of drugs includes morphine, heroin, codeine, and synthetic analgesics such as pethidine, methadone, and dipipanone. The pharmacological effects of opioids are mediated primarily through interaction with specific opioid receptors, with morphine and heroin being quite selective for the μ-opioid-receptor type. The main medical use of opioids is for their powerful analgesic actions; they are misused for their euphoriant and anxiolytic effects.

In the past morphine was misused widely in Western countries, but has been largely replaced as a drug of misuse by heroin, which has a particularly powerful euphoriant effect, especially when taken intravenously.

Epidemiology

The Psychiatric Morbidity Survey reported that in households in England the prevalence of illicit opiate use over the last year was about 0.3%, and the rate of dependence was 0.1%. The lifetime rate of illicit opiate use was almost 2% (McManus et al., 2007). Higher rates would be expected in the homeless and in prisons.

Use and misuse

The epidemiological data indicate that many people use heroin without becoming dependent on it. However, there is no doubt that repeated heroin use can lead to the rapid development of dependence and marked physiological tolerance. As well as the intravenous route, opioid users may employ other methods of administration—for example, subcutaneous administration (‘skin-popping’) or sniffing (‘snorting’). Heroin may also be heated on a metal foil and inhaled (‘chasing the dragon’). Heroin users may change their customary method of drug administration from time to time. From the perspective of harm reduction, methods that avoid intravenous administration are preferable.

Clinical effects

As well as euphoria and analgesia, opioids cause respiratory depression, constipation, reduced appetite, and low libido. Tolerance develops rapidly, leading to the need for an increasing dosage. Tolerance does not develop equally to all of the effects, and constipation often continues when the other effects have diminished. When the drug is stopped, tolerance diminishes rapidly, so a dose taken after a period of abstinence has greater effects than it would have had previously. This loss of tolerance can result in dangerous—sometimes fatal—respiratory depression when a previously tolerated dose is resumed after a drug-free interval (e.g. after a stay in hospital or prison).

Withdrawal from opioids

Withdrawal symptoms from opioids may include the following:

• intense craving for the drug

• restlessness and insomnia

• pain in muscles and joints

• running nose and eyes

• abdominal cramps, vomiting, and diarrhoea

• piloerection, sweating dilated pupils, and raised pulse rate

• disturbance of temperature control.

These features usually begin about 6 hours after the last dose, reach a peak after 36–48 hours, and then wane. Withdrawal symptoms rarely threaten the life of someone in reasonable health, although they cause great distress and so drive the person to seek further supplies of the drug.

Methadone

Methadone is approximately as potent, weight for weight, as morphine. It causes cough suppression, constipation, and depression of the central nervous system and of respiration. Pupillary constriction is less marked. The withdrawal syndrome is similar to that of heroin and morphine, and is at least as severe. Because methadone has a long half-life (1–2 days), symptoms of withdrawal may begin only after 36 hours and reach a peak after 3–5 days. For this reason, methadone is often used to replace heroin in patients who are dependent on the latter drug.

The natural course of opioid dependence

Longer-term follow-up studies of opioid misusers have revealed that in most cases the disorder appears to run a chronic relapsing and remitting course, with a significant mortality (10–20%) over 10 years. Nevertheless, up to 50% of opioid users have been found to be abstinent at 10-year follow-up, which suggests a trend towards natural remission in survivors (Robson, 2009).

Deaths are not infrequently due to accidental overdosage, often related to loss of tolerance after a period of enforced abstinence (see above). Suicide is also a common cause of death. Deaths from HIV infection and hepatitis have become more frequent in recent years. Factors associated with a good outcome include substantial periods of employment and marriage. Abstinence is often related to a change in life circumstances. This is illustrated by the report of 95% abstinence among soldiers who returned to the USA after becoming dependent on opioids during service in the Vietnam War (Robins, 1993).

Prevention

Because dependence develops rapidly and treatment of dependent opioid misusers is unsatisfactory, preventive measures (see p. 469) are particularly important with regard to this group of drugs.

Treatment of crisis

Opioid misusers may present in crisis to a doctor in any of three situations. First, when their supplies have run out, they may seek drugs either by requesting them directly or by feigning a painful disorder. Although withdrawal symptoms are very unpleasant, so that the misuser will go to great lengths to obtain more drugs, these symptoms are not usually dangerous to an otherwise healthy person. Therefore it is best to offer drugs only as the first step of a planned maintenance or withdrawal programme. This programme is described in the following sections. The second form of crisis is drug overdose. This requires medical treatment, directed in particular towards any respiratory depression caused by the drug. The third form of crisis is an acute complication of intravenous drug usage, such as local infection, necrosis at the injection site, or infection of a distant organ, often the heart or liver.

Planned withdrawal (detoxification) (see Box 17.14)

The severity of withdrawal symptoms depends on psychological as well as pharmacological factors. Therefore the psychological management of the patient during withdrawal is as important as the drug regimen. The speed of withdrawal should be discussed with the patient, in order to establish a timetable which is neither so rapid that the patient will not collaborate, nor so protracted that the state of dependence is perpetuated. During withdrawal, much personal contact is needed to reassure the patient; the relationship that is formed in this way can be important in later treatment. The duration of opioid detoxification is usually about 4 weeks in a residential setting and up to 12 weeks in a community setting.

Box 17.14 Pharmacological management of opioid withdrawal

• If short-term, non-opiate treatment is desired, use an α2-adrenoceptor agonist such as lofexidine.

• Buprenorphine can be used for short-term opioid withdrawal.

• Methadone treatment for withdrawal can be successful, but needs to be carried out slowly with a gradual tapering of the dose.

From National Institute for Health and Clinical Excellence (NICE) (2007c).

When the dose is low, opioids can be withdrawn more quickly while giving symptomatic treatment for the withdrawal effects. Drugs such as loperamide or metoclopr-amide can be useful for gastrointestinal symptoms. Non-steroidal analgesics may be useful for aches and pains. Another drug that may be useful is the α2-adrenoceptor agonist, lofexidine. Lofexidine has a similar action to clonidine, but causes less hypotension and is preferred for managing opiate withdrawal.

When the daily dose of heroin is high, it may be necessary to prescribe an opioid, reducing the dose gradually. One approach is to use methadone, which has a more gradual action. The difficulty lies in judging the correct dose of methadone, because patients may either overstate their use of heroin because they fear the withdrawal symptoms, or understate it in an attempt to avoid censure. In addition, as noted below, the strength of street drugs varies.

Methadone should be given in a liquid form to be taken by mouth. The initial methadone dose is normally 10–40 mg daily, depending on the patient’s usual consumption. Users with evidence of opioid tolerance may require dosing at the higher end of this range. If 4 hours after an initial dose there is evidence of withdrawal symptoms, a supplementary dose may be given, but caution is needed because methadone is a long-acting drug, and accumulation and toxicity could result. Street heroin varies in potency in different places and at different times. Therefore, if possible, advice about the equivalent dose of methadone should be obtained from a doctor with experience of treating drug dependence. The rate of methadone reduction depends on the clinical circumstances and the patient’s clinical responses. The most rapid regimen may take about 10 days to 3 weeks, but slower reductions over several months may sometimes be appropriate.

Buprenorphine, a partial agonist at opioid receptors, can also be used to manage opioid withdrawal. Again, tapering doses are used at a rate that has been agreed with the patient. Buprenorphine is often well tolerated, but care needs to be taken when starting treatment, especially in the case of patients who are transferring from metha-done. This is because the partial agonist action of the drug may precipitate acute withdrawal in patients who are transferring from higher doses of methadone (more than 30 mg) or heroin. This can usually be avoided by beginning treatment when the patient is already in mild withdrawal.

The opioid antagonist, naltrexone, has been used in a procedure known as rapid opioid detoxification in conjunction with sedation and sometimes general anaesthesia (ultra-rapid detoxification). The use of general anaesthesia during detoxification is not recommended because of serious safety concerns. Rapid opioid detoxification is a possible option, but requires a high level of nursing support because of the increased severity of withdrawal symptomatology and the need to monitor the airway of a sedated patient (National Institute for Health and Clinical Excellence, 2007c).

When opioid drugs are prescribed to drug-dependent patients, there is the possibility of diversion of the medication to the illegal market. This can be avoided by supervision of consumption of each daily dose—for example, by nursing or pharmacy staff. This practice also reduces the risk of overdose, and the daily personal contact probably also has other therapeutic benefits. It is generally regarded as good practice at least while treatment is being established, although daily attendance can be difficult for patients who are in full-time employment. In general, opiate detoxification can take place in the community, but inpatient management should be considered for patients who have not benefited from previous attempts at detoxification in the community, or who need a high level of nursing and medical care because of comorbid physical or psychiatric problems or polydrug abuse, or those who have significant social problems.

During and after opiate withdrawal it is important to consider and institute a suitable plan of psychosocial intervention as outlined above. The current guideline from the National Institute for Health and Clinical Excellence (2007b) recommends consideration of contingency management (see p. 471).

Pregnancy and opioid dependence

The babies of women who misuse opioids are more likely than other babies to be premature and of low birth weight. They may also show withdrawal symptoms after birth, including irritability, restlessness, tremor, and a high-pitched cry. These signs appear within a few days of birth if the mother was taking heroin, but are delayed if she was taking methadone, which has a longer half-life in the body. Low birth weight and prematurity are not necessarily directly related to the drug, as poor nutrition and heavy smoking are common among heroin misusers.

Later effects have been reported, with the children of opioid-dependent mothers being more likely, as toddlers, to be overactive and to show poor persistence. However, these late effects may result from the unsuitable family environment rather than from a lasting effect of the intrauterine exposure to the drug.

The pregnancies of women who are in methadone maintenance programmes have a better outcome than those of women who use opioids but are not in such programmes. Some pregnant women request detoxification, but there are significant risks to the baby if this is carried out in the first or third trimester. The main aim of treatment in the first trimester is to engage the mother in a multidisciplinary care programme that will include stabilization on a suitable dose of methadone, avoidance of illegal drug use, and a high level of antenatal care. Patients who are receiving buprenorphine can remain on this treatment. Detoxification may be carried out in the second trimester, employing small frequent reductions of methadone or buprenorphine (Department of Health, 2007b; National Institute for Health and Clinical Excellence, 2007c).

Maintenance treatment for opioid dependence

As described above, withdrawal from opioids is the preferred treatment option, but if this is not possible, maintenance treatment, usually with methadone, may reduce the physical and social harm associated with the intravenous use of illegal drug supplies. The principle of this treatment is explained on p. 472. Instead of heroin, methadone is prescribed as a liquid preparation formulated so as to discourage attempts to inject it.

Methadone maintenance treatment. There is good evidence from randomized studies that methadone maintenance treatment decreases the use of illegal opioids and reduces criminal activity. In addition, patients in methadone maintenance programmes show less risky injecting behaviours and lower rates of HIV infection. Overall, patients who are receiving methadone maintenance treatment are approximately three times more likely to stay in treatment, and are about two-thirds less likely to use illegal heroin (Department of Health, 2007b; National Institute for Health and Clinical Excellence, 2007d).

Methadone doses of 20–40 mg daily have been widely advocated as appropriate for maintenance treatment, but there is evidence that higher doses (60–120 mg daily) are associated with lower rates of illegal opioid use and improved retention in the therapeutic programme (Department of Health, 2007b). The latter is associated with an improved therapeutic outcome. The best approach is probably to have a flexible dosing policy, bearing in mind the potential toxicity of methadone in patients whose tolerance is unknown or difficult to assess. Generally it is better to start treatment with lower doses initially (not more than 40 mg daily), and to increase the dose over a number of weeks, titrating against the presence of withdrawal symptoms. It should be remembered that methadone levels continue to increase for about 5 days after the last dosage adjustment. Practical advice on methadone treatment has been provided by the National Institute for Health and Clinical Excellence (2007d) and the Department of Health (2007b).

There is also a growing evidence base for the use of buprenorphine as an alternative to methadone for maintenance treatment for opioid users, although there is less consensus on appropriate dosing. In general, doses of 12–16 mg are used in longer-term prescribing. The same principles of treatment apply as in methadone prescribing. Theoretically, because of its partial agonist properties, buprenorphine may be safer in overdose than metha-done and less liable to illegal diversion. However, whether this is in fact the case has not yet been clearly demonstrated.

The concerns about diversion of prescribed opioid drugs, and the risk of overdose, have been described above in the section on management of opioid withdrawal. They also apply in maintenance treatment, and daily supervised consumption is commonly continued for a proportion of patients in maintenance treatment. A UK survey showed that supervision of methadone administration produced a fourfold decrease in deaths due to methadone overdose (Strang et al., 2010).

Naltrexone is a long-acting opioid antagonist which is used to help to prevent relapse in detoxified opioid-dependent patients. Although naltrexone treatment may have a role in certain dependent individuals who are highly motivated, such as doctors recovering from opioid dependence, or patients engaged in structured programmes associated with the criminal justice system, its benefit in the wider community of opioid users is less well established (Kirchmayer et al., 2003).

Therapeutic community methods

These forms of treatment aim to produce abstinence by effecting a substantial change in the patient’s attitudes and behaviour. Drug taking is represented as a way of avoiding pre-existing personal problems, and as a source of new ones. Group therapy and communal living are combined in an attempt to produce greater personal awareness, more concern for others, and better social skills. In most therapeutic communities some of the staff have previously been dependent on drugs, and so are often better able to gain the confidence of patients in the early stages of treatment.

Anxiolytic and hypnotic drugs

The most frequently misused drugs in this group are now the benzodiazepinesBarbiturates are little prescribed and their misuse has fallen. Other drugs in this group that are currently misused include clomethiazole and chloral. The clinical effects of these drugs are thought to result from their ability to facilitate brain GABA function. Benzodiazepines produce these effects by binding to a specific benzodiazepine receptor.

Benzodiazepines

These drugs were in therapeutic use for many years before it became apparent that their prolonged use could lead to tolerance and dependence, with a characteristic withdrawal syndrome. The withdrawal syndrome includes the following:

• anxiety symptoms—anxiety, irritability, sweating, tremor, and sleep disturbance

• altered perception—depersonalization, derealization, hypersensitivity to stimuli, abnormal body sensations, and abnormal sensation of movement

• other features (rare)—depression, suicidal behaviour, psychosis, seizures, and delirium tremens.

Epidemiology. Benzodiazepine use is extremely widespread—for example, it has been estimated that about 10% of the population of Europe and the USA use benzodiazepines as anxiolytics or hypnotics. Over the last few years there has been in decline in the prescription of benzodiazepines for anxiety. Most long-term users are older women. However, there is a significant misuse problem among younger people, often associated with intravenous administration and polysubstance misuse. A significant proportion of people who are dependent on alcohol are also dependent on benzodiazepines. The Psychiatric Morbidity Survey reported that in households in England the prevalence of illegal tranquillizer use during the previous year was 0.7%, while 0.3% of those surveyed described themselves as dependent on tranquillizers (McManus et al., 2007).

Dependence. Dependence on benzodiazepines often results from prolonged medical use, but may also result from the availability of benzodiazepines as street drugs because of their euphoriant and calming effects. The withdrawal syndrome closely resembles the anxiety symptoms for which the drugs are usually prescribed. Thus if symptoms appear after the dose of benzodiazepine has been reduced, the doctor may revert to a higher dosage in the mistaken belief that these symptoms indicate a persistent anxiety disorder. It has been estimated that about one-third of patients who take a benzodiazepine at therapeutic doses for more than 6 months may become dependent (Lingford-Hughes et al., 2004).

Treatment. Treatment of dependence usually consists of gradual withdrawal over a period of at least 8 weeks, combined with supportive counselling. Withdrawal appears to be more severe from benzodiazepines that have short half-lives and high potency at the benzodiazepine receptor. For this reason it is often suggested that patients who are taking such compounds should be switched to longer-acting drugs such as diazepam before withdrawal is attempted. For patients who have difficulty withdrawing using these measures, anxiety management may be useful (see p. 584).

Current advice is that the dose of benzodiazepine should be lowered by about one-eighth every 2 weeks. However, if a patient experiences troublesome withdrawal symptoms, the dose can be maintained or even temporarily increased until the symptoms settle. If a patient has been misusing benzodiazepines and taking very high doses, it may be difficult to identify an appropriate starting dose. In general, patients should not be given more than 40–60 mg diazepam daily. This dose should gradually be reduced by about half over 6 weeks (Department of Health, 2007b).

Many patients experience their most troublesome withdrawal symptoms once the benzodiazepine dose has been completely tapered off. Symptoms usually subside over the next few weeks, although the time course can be irregular and some symptoms, such as muscle spasm, may not appear until other features of withdrawal have largely disappeared. A few patients continue to experience withdrawal-like symptoms for months or even years after cessation of benzodiazepines (prolonged withdrawal syndrome).

Prevention. The prevention of benzodiazepine dependence lies in the restriction of prescribing. Psychological treatments are effective for anxiety disorders (see p. 584), and non-pharmacological approaches to insomnia are also beneficial (see p. 362). If benzodiazepines are prescribed, this should be for the short-term relief of symptoms that are severely disabling or distressing. In some patients who are already long-term users, the balance of benefit and risk will favour continued prescribing, but these patients should be regularly reviewed and the daily dose of diazepam should not exceed 30 mg (Department of Health, 2007b). Advice from a general practitioner can be sufficient to persuade 20–40% of long-term benzodiazepine users to reduce their daily dose or discontinue treatment.

For further information about benzodiazepine dependence and its treatment, see Lingford-Hughes et al. (2004).

Barbiturates

Barbiturate prescribing has greatly diminished over the last decade as newer anxiolytic and antidepressant agents have become preferred, so illegal use is becoming rare. Previously many people who became dependent on barbiturates began taking the drug because it had been prescribed as a hypnotic. Some barbiturates reached young drug misusers who administered them intravenously by dissolving capsules. Polysubstance misuse with barbiturates was common.

Withdrawal. Abrupt withdrawal of barbiturates from a dependent patient is dangerous. It may result in a delirium, like that which occurs after alcohol withdrawal, and may lead to seizures and sometimes to death due to cardiovascular collapse. Therefore if it is necessary to withdraw a person who has been taking doses substantially in excess of the therapeutic range, inpatient detoxification is advisable. However, if a patient has been taking a therapeutic dose, slow withdrawal as an outpatient may be considered.

Cannabis

Cannabis is derived from the plant Cannabis sativa. It is consumed either as the dried vegetative parts in the form known as marijuana or grass, or as the resin secreted by the flowering shoots of the female plant. Cannabis contains several pharmacologically active substances, of which the most powerful psychoactive compound is δ-9-tetrahydrocannabinol (THC). It seems likely that the pharmacological effects of cannabinols are mediated through interaction with a specific cannabinoid receptor in the central nervous system. The endogenous ligand for these receptors is probably anandamide (for a review of the pharmacology of cannabis, see Howlett et al., 2004). Over the last decade more potent cannabis preparations (known as ‘skunk’) have become widely available which have higher levels of THC and presumably a greater risk of adverse effects.

Epidemiology. In some parts of North Africa and Asia, cannabis products are consumed in a similar way to alcohol in Western society. In North America and Europe the intermittent use of cannabis by young people is widespread. The Psychiatric Morbidity Survey reported that in households in England the lifetime use of cannabis was about 23%, with 7.5% of those surveyed reporting use in the last year, and 2.7% meeting the criteria for cannabis dependence (McManus et al., 2007).

Clinical effects. The effects of cannabis vary with the dose, the person’s expectations and mood, and the social setting. Users sometimes describe themselves as ‘high’ but, like alcohol, cannabis seems to exaggerate the pre-existing mood, whether that was exhilaration or depression. Users report an increased enjoyment of aesthetic experiences, and distortion of the perception of time and space. There may be reddening of the eyes, dry mouth, tachycardia, irritation of the respiratory tract, and coughing. Cannabis intoxication can lead to dangerous driving.

Adverse effects. No serious adverse effects have been demonstrated among those who use cannabis intermittently in small doses. Although there is no positive evidence of teratogenicity, cannabis has not been proved safe during the first 3 months of pregnancy. Inhaled cannabis smoke irritates the respiratory tract and is potentially carcinogenic. The most common adverse psychological effect of acute cannabis consumption is anxiety. Mild paranoid ideationis also not uncommon. At higher doses, toxic confusional states and occasionally psychosis in clear consciousness may occur.

Cannabis and mental illness. It is well established that cannabis can modify the course of an established schizophrenic illness, with evidence from a number of studies that users are more likely to experience psychotic episodes and relapse (Hall and Dengenhardt, 2011). The question of whether cannabis use can predispose to the later development of schizophrenia has been more controversial. Andreasson et al. (1987) followed up 45 570 Swedish conscripts for 15 years. They found that the relative risk of developing schizophrenia was 2.5 times higher in individuals who used cannabis, and that the relative risk for heavy users was six times higher. Although these data suggest that cannabis could be a risk factor for the development of schizophrenia, it is also possible that those who are predisposed to develop schizophrenia are also predisposed to misuse cannabis.

However, more recent prospective cohort studies that have adjusted for various confounding factors continue to demonstrate an increased risk of new-onset psychotic symptoms in young people who use cannabis (Kuepper et al., 2011). The increase in risk of psychosis is about twofold in individuals without other risk factors for schizophrenia (rising from about 7 in 1000 to 14 in 1000 in regular users). However, in people at high risk of schizophrenia due, for example, to a strong family history, a twofold increase in risk could be important, perhaps raising the risk of psychosis from about 1 in 10 to 1 in 5 (Hall and Dengenhardt, 2011). Arseneault et al. (2004) calculated that the removal of cannabis from society would prevent about 8% of cases of schizophrenia.

There has also been concern that cannabis use among teenagers might increase the risk of other poor psychosocial outcomes, such as mood disorder, poor educational performance, job instability, and uptake of more harmful illegal drugs. However, a systematic review found that the evidence that cannabis is a major cause of psychosocial harm in young people was inconsistent and likely to be confounded by other factors, such as childhood adversity (Macleod et al., 2004). It is also said that chronic use of cannabis can lead to a state of apathy and indolence (an amotivational state). However, this proposal has not been confirmed by epidemiological studies. It is possible that the symptoms and signs of the amotivational state could reflect chronic intoxication (Hall, 2009).

Tolerance and dependence. There is evidence that tolerance to the effects of cannabis can occur in individuals who are exposed to high doses for a prolonged period of time, but it is much less evident in those who use small or intermittent doses. However, some patients do report inability to control cannabis use despite personal and social harm resulting from it. Withdrawal from high doses of cannabis gives rise to a syndrome of irritability, nausea, insomnia, and anorexia. These symptoms are generally mild in nature. The best way to manage cannabis dependence is unclear, but psychosocial interventions are commonly provided. Although abstinence may be difficult to achieve, treatment does appear to lower cannabis use und the associated harms.

For a review of the adverse effects of cannabis use, see Hall (2009), and for an outline of the management of cannabis dependence, see Winstock et al. (2010).

Stimulant drugs

These drugs include amphetamines, and related substances such as methylphenidate. Cocaine is also a stimulant drug, but is considered separately in the next section.

Amphetamines

Amphetamines have been largely abandoned in medical practice, apart from their use for the treatment of attention deficit disorder (see p. 654) and narcolepsy (see p. 363). The psychomotor stimulant effects of amphetamines are believed to result from their ability to release and block the reuptake of dopamine and noradrenaline.

Epidemiology. Amphetamines are currently used rather less than cocaine in the UK, although they were used more previously. The Psychiatric Morbidity Survey reported that in households in England the lifetime use of amphetamines was about 8.6%, with 0.7% reporting use in the last year, and 0.2% of those surveyed meeting the criteria for amphetamine dependence (McManus et al., 2007).

In the past, addiction to stimulant drugs arose chiefly from injudicious prescribing. However, most amphetamines are now illegally synthesized and used as a ‘street drug’, known as ‘speed’ or ‘whizz.’ As well as being taken orally or intravenously, amphetamines can also be ‘snorted’ (taken like snuff). A pure form of amphetamine (‘ice’) can be smoked or injected, and is said to produce particularly powerful effects.

Clinical effects. Apart from their immediate effect on mood, amphetamines cause over-talkativeness, overactivity, insomnia, dryness of the lips, mouth, and nose, and anorexia. The pupils dilate, the pulse rate increases, and the blood pressure rises. With large doses there may be cardiac arrhythmia, severe hypertension, cerebrovascular accident, and occasionally circulatory collapse. At increasingly high doses, neurological symptoms such as seizures and coma may occur. Acute adverse psychological effects of amphetamines include dysphoria, irritability, insomnia, and confusion. Anxiety and panic can also be present. Obstetric complications include miscarriage, premature labour, and placental abruption (see Table 17.10).

Amphetamine-induced psychosis. Prolonged use of high doses of amphetamines may result in repetitive stereotyped behaviour (e.g. repeated tidying). A paranoid psychosis that has been likened to paranoid schizophrenia may also be induced by prolonged high doses. The features include persecutory delusions, auditory and visual hallucinations, and sometimes hostile and dangerously aggressive behaviour (Connell, 1958). Usually the condition subsides within about a week, but occasionally it persists for months. It is not certain whether these prolonged cases represent true drug-induced psychoses, schizophrenia provoked by the amphetamine, or are merely coincidental. Whatever the nature of the association, it is not uncommon for patients with a history of amphetamine misuse to present to general psychiatric services. The ability of amphetamines to provoke psychosis has been one of the observations that has supported the dopamine hypothesis of schizophrenia (see Chapter 11).

Table 17.10 Some complications of amphetamine and cocaine misuse

Medical

Cardiovascular—hypertension, stroke, arrhythmias, myocardial infarction

Infective—abscesses, septicaemia, hepatitis, HIV

Obstetric—reduced fetal growth, miscarriage, premature labour, placental abruption

Other—weight loss, dental problems, epilepsy, general neglect

Psychiatric

Anxiety, depression, antisocial behaviour, paranoid psychosis

Tolerance and dependence. From the epidemiology of amphetamine use, it seems that many recreational users do not progress to misuse and dependence. In more persistent users, tolerance to amphetamines leads to higher doses of the drug being taken. A withdrawal syndrome (‘crash’) of varying severity follows cessation of amphetamine use. In mild cases it consists mainly of low mood and decreased energy. In some cases, particularly in heavy users, depression can be severe, and accompanied by anxiety, tremulousness, lethargy, fatigue, and nightmares. Craving for the drug may be intense, and suicidal ideation may be prominent. Dependence on amphetamines can develop quickly. Dependence on stimulant drugs may be recognized from a history of overactivity and high spirits alternating with inactivity and depression. Whenever amphetamine use is at all likely, a urine sample should be taken for analysis as soon as possible because these drugs are quickly eliminated.

Prevention and treatment. Prevention of amphetamine misuse depends on restriction of the drugs and careful prescribing. Doctors should be wary of newly arrived patients who purport to suffer from narcolepsy.

Treatment of acute overdoses requires sedation and management of hyperpyrexia and cardiac arrhythmias. Most toxic symptoms, including paranoid psychoses, resolve quickly when the drug is stopped. An antipsychotic drug may be needed to control florid symptoms.

The treatment of amphetamine dependence is difficult, as craving for the drug can be intense. Abstinence is the usual goal. and to achieve this a full range of social and psychological interventions may be needed (see above). Benzodiazepines may be helpful for managing acute distress caused by a severe withdrawal syndrome. Antidepressants do not appear to be effective in promoting abstinence, although they may be appropriate for treatment of a persistent depressive disorder. Abstinence-based programmes are not suitable for all misusers, and in view of the considerable harm that is associated with severe intravenous misuse, some specialist centres have undertaken maintenance treatment with oral amphetamine. There is no clear evidence base for this practice, and current guidance from the Department of Health is that it should not ‘ordinarily be provided’ (Department of Health, 2007b).

Cocaine

Cocaine is a central nervous stimulant with effects similar to those of amphetamines (described above). It a particularly powerful positive reinforcer in animals, and causes strong dependence in humans. These latter effects probably stem from the ability of cocaine to block the reuptake of dopamine into presynaptic dopamine terminals. This leads to substantial increases in extracellular levels of dopamine in the nucleus accumbens, and consequent activation of the physiological ‘reward system’ (Lingford-Hughes et al., 2010).

Cocaine is administered by injection, by smoking, and by sniffing into the nostrils. The latter practice sometimes causes perforation of the nasal septum. In ‘freebasing’, chemically pure cocaine is extracted from the street drug to produce ‘crack’, which has a very rapid onset of action, particularly when inhaled.

Epidemiology. The Psychiatric Morbidity Survey reported that in households in England the lifetime use of cocaine was about 6.3%, with 2.5% of those surveyed reporting use in the last year and 0.4% meeting the criteria for cocaine dependence.

Clinical effects. The psychological effects of cocaine include excitement, increased energy, and euphoria. This can be associated with grandiose thinking, impaired judgement, and sexual disinhibition. Higher doses can result in visual and auditory hallucinations. Paranoid ideation may lead to aggressive behaviour. More prolonged use of high doses of cocaine can result in a paranoid psychosis with violent behaviour. This state is usually short-lived, but may be more enduring in those with a pre-existing vulnerability to psychotic disorder. Formication (‘cocaine bugs’)—a feeling as if insects are crawling under the skin—is sometimes experienced by heavy cocaine users.

The physical effects of cocaine include increases in pulse rate and blood pressure. Dilation of the pupils is often prominent. Severe adverse effects of cocaine use include cardiac arrhythmias, myocardial infarction, myocarditis, and cardiomyopathy. Cocaine use has also been associated with cerebrovascular disease, including cerebral infarction, subarachnoid haemorrhage, and transient ischaemic attacks. Seizures and respiratory arrest have been reported. Obstetric complications include miscarriage, placental abruption, and premature labour.

Tolerance and dependence. In persistent users, tolerance of the effects of cocaine develops and a withdrawal syndrome similar to that seen following withdrawal of amphetamines can occur. After acute cocaine use, the ‘crash’ consists of dysphoria, anhedonia, anxiety, irritability, fatigue, and hypersomnolence. If the preceding cocaine use has been relatively mild, such symptoms resolve within about 24 hours. After more prolonged use, the symptoms are more severe and extended, and are associated with intense craving, depression, and occasionally severe suicidal ideation. Craving for cocaine can re-emerge after months of abstinence, particularly if the individual is exposed to psychological or social cues previously associated with its use.

Treatment. Acute intoxication may require sedation with benzodiazepines or, in severe cases, an antipsychotic agent. Concurrent medical crises such as seizures or hypertension should be managed in the usual way.

As with amphetamines, the treatment of cocaine dependence is difficult because of the intense craving associated with abstinence from the drug. For moderate cocaine users it may be sufficient to provide psychological and social support on an outpatient basis. Heavy and chaotic users with strong dependence will need more intensive management, perhaps in a residential setting. There is little evidence to support substitute pharmacological treatments to date, although several approaches have been evaluated. Various psychosocial approaches can be helpful for patients with cocaine dependence. These include cognitive–behavioural therapies, contingency management, and programmes that incorporate twelve-step approaches. With regard to individual treatment programmes, it is worth noting that people who misuse cocaine often misuse other drugs, such as opioids and alcohol.

MDMA (‘ecstasy’)

The recreational use of 3,4 methylenedioxymethamphetamine (MDMA), also known as ‘ecstasy’, increased rapidly at the end of the twentieth century but might now be declining to some extent. In 1998, about 5% of 16- to 24-year-olds reported using ecstasy in the last year, and in 2002 the number had risen to about 7% (Aust et al., 2002). In 2007, the Psychiatric Morbidity Survey found a corresponding figure of 3.4% (McManus et al., 2007). Lifetime use of ecstasy in this survey across all ages was about 5%. Ecstasy is a synthetic drug that is classified in the DSM-IV substance list as a hallucinogen. However, it has stimulant as well as mild hallucinogenic properties. It is usually taken in tablet or capsule form in a dose of about 50–150 mg. Given in this way, its effects last for about 4–6 hours. Like amphetamines, ecstasy increases the release of dopamine, but it also releases 5–hydroxytryptamine (5-HT), which may account for its hallucinogenic properties.

Clinical effects. Ecstasy produces a positive mood state, with feelings of euphoria, sociability, and intimacy. It also produces sensations of newly discovered insights and heightened perceptions. The physical effects of ecstasy include loss of appetite, tachycardia, bruxism, and sweating. Tolerance of successive doses of ecstasy develops quickly. Weekend users describe a midweek ‘crash’ in mood which may represent withdrawal effects.

Adverse reactions. Rarely, ecstasy can cause severe adverse reactions, and deaths due to hyperthermia and its complications have been reported in healthy young adults. Hyperthermia probably results from the effect of ecstasy in increasing brain 5-HT release, together with the social setting in which the drug is customarily taken (crowded parties with prolonged and strenuous dancing). Deaths have also been reported due to cardiac arrhythmias, although pre-existing cardiac disease may have played a role. Intracerebral haemorrhage has occurred in ecstasy users, probably as a consequence of hypertensive crises. Cases of toxic hepatitis could reflect impurities in manufacture or an idiosyncrasy in metabolism.

The use of ecstasy has been associated with acute and chronic paranoid psychoses. However, as with other drug-induced psychotic states, it is not clear how far such disorders represent idiosyncratic reactions of vulnerable individuals. There are also reports of ‘flashbacks’, which are the recurrence of abnormal experiences weeks or months after drug ingestion. Such effects have been reported with other hallucinogens (see below). It is possible that repeated use of ecstasy may increase the risk of adverse psychiatric outcomes such as depression, anxiety, and depersonalization.

In experimental animals, including primates, repeated treatment with ecstasy causes degeneration of 5-HT nerve terminals in the cortex and forebrain. Therefore it is possible that such effects could occur in humans, and some brain-imaging studies have shown changes in serotonin transporter binding consistent with 5-HT neuronal damage; however, the findings are not consistent. Whether such a change could be associated with long-term neuropsychological or psychiatric sequelae is not known, but there is evidence for impairment of verbal memory in former ecstasy users.

Prevention and harm reduction. Although the risk of serious harm following acute ecstasy use appears to be low, it is important to inform potential users about the acute risks and the potential long-term hazard of neurotoxicity, cognitive impairment, and adverse longer-term psychiatric sequelae. Consumption of large doses and pre-existing psychiatric disorder are likely to be associated with increased risk of adverse reactions. Education may also help users to avoid heatstroke by encouraging them to take breaks from dancing and to consume sufficient isotonic replacement fluid during vigorous exercise. However, the consumption of large amounts of water has sometimes caused death due to hyponatraemia.

For a review of ecstasy and the complications of its use, see Winstock and Schifano (2009).

Hallucinogens

Hallucinogens are sometimes known as psychedelics, but we do not recommend this term because it does not have a single clear meaning. The term psychotomimetic is also used, because the drugs produce changes that bear some resemblance to those of psychotic symptoms. However, the resemblance is not close, so we do not recommend this term either.

The synthetic hallucinogens include lysergic acid diethylamide (LSD), dimethyltryptamine, and methyldimethoxyamphetamine. Of these drugs, LSD is encountered most often in the UK. Hallucinogens also occur naturally in some species of mushroom, and varieties containing psilocybin are consumed for their hallucinogenic effects. The mode of action of hallucinogenic drugs is unclear, but most of them act as partial agonists at brain 5-HT2A receptors.

Epidemiology. The Psychiatric Morbidity Survey reported that in households in England the lifetime use of LSD was 3.5%, while that of magic mushrooms was 5.0%. The corresponding figures for use in the last year were 0.2% and 0.6%, respectively (McManus et al., 2007).

Clinical effects. The effects of LSD have been most well studied, and will be described here. The physical actions of LSD are variable. There are initial sympathomimetic effects—heart rate and blood pressure may increase and the pupils may dilate. However, overdosage does not appear to result in severe physiological reactions.

In predisposed individuals, the hypertensive effects of hallucinogens can cause adverse myocardial and cerebrovascular effects. The psychological effects develop within a period of 2 hours after LSD consumption, and generally last from 8 to 14 hours. The most remarkable experiences are distortions or intensifications of sensory perception. There may be confusion between sensory modalities (synaesthesia), with sounds being perceived as visual, or movements being experienced as if heard. Objects may be seen to merge with one another or to move rhythmically. The passage of time appears to be slowed, and experiences seem to have a profound meaning.

A distressing experience may be distortion of the body image, with the person sometimes feeling that they are outside their own body. These experiences may lead to panic, with fears of insanity. The patient’s mood may be one of exhilaration, distress, or acute anxiety. According to early reports, behaviour could be unpredictable and extremely dangerous, with users sometimes injuring or even killing themselves as a result of behaving as if they were invulnerable. Since then there may have been some reductions in such adverse reactions, possibly because users are more aware of the dangers and take precautions to ensure support from other people during a ‘trip.’

Whenever possible, adverse reactions should be managed by ‘talking down’ the user, explaining that the alarming experiences are due to the drug. If there is not time for this, an anxiolytic such as diazepam should be given and is usually effective. Tolerance of the psychological effects of LSD can occur, but a withdrawal syndrome has not been described. It is uncertain whether dependence occurs, but it is likely to be rare.

It has been argued that the use of LSD can cause long-term abnormalities in thinking and behaviour, or even schizophrenia, but the evidence for this is weak. However, flashbacks (i.e. the recurrence of psychedelic experience weeks or months after the drug was last taken) are a recognized event. A number of medications, including benzodiazepines and anticonvulsants, have been reported to be helpful in the management of flashbacks, but there have been no controlled trials (Abraham, 2009).

Phencyclidine and ketamine

Phencyclidine is sufficiently different from the hallucinogens in its actions to require a separate description. It can be synthesized easily, and is taken by mouth, smoked, or injected. Phencyclidine was developed as a dissociative anaesthetic, but its use was abandoned because of adverse effects such as delirium and hallucinations. It is related to the currently used anaesthetic agent ketamine. Ketamine is also misused, and has similar effects to those of phencyclidine. However, ketamine has a shorter half-life than phencyclidine and is less likely than the latter to be associated with grossly disturbed behaviour.

Both phencyclidine and ketamine antagonize neurotransmission at N-methyl-D-aspartate (NMDA) receptors, which may account for their hallucinogenic effects. The psychological effects of ketamine in healthy volunteers have been used to model some of the clinical symptoms and cognitive changes that are seen in patients with schizophrenia, and are discussed on p. 278. Ketamine has also aroused interest because of its unexpected ability to produce a striking temporary remission of depression in treatment-refractory patients.

Phencyclidine is widely available in the USA but is little used in the UK. Most users of phencyclidine also use other drugs, particularly alcohol and cannabis. Ingestion of phencyclidine may be inadvertent, as it is often added to other street drugs to boost their effects. Ketamine is growing in popularity and is mainly used in the ‘club scene’ (Winstock and Schifano, 2009). Ketamine has a good safety profile when used as an anaesthetic, for which purpose it is given intravenously. Illicit use of ketamine can involve intravenous use or ‘snorting.’ When taken by either of these routes the drug has short duration of action (about 1 to 2 hours).

Clinical effects. Small doses of phencyclidine produce drunkenness, with analgesia of the fingers and toes, and even anaesthesia. Intoxication with the drug is prolonged, the common features being agitation, depressed consciousness, aggressiveness and psychotic-like symptoms, nystagmus, and raised blood pressure. With high doses there may be ataxia, muscle rigidity, convulsions, and absence of response to the environment even though the eyes are wide open. Phencyclidine can be detected in the urine for 72 hours after it was last taken.

If serious overdoses are taken, sympathomimetic crises may occur with hypertensive heart failure, cerebrovascular accident, or malignant hyperthermia. Status epilepticus may appear. Rhabdomyolysis can lead to renal failure. Fatalities have been reported, due mainly to hypertensive crisis but also to respiratory failure or suicide. Other people may be attacked and injured. Chronic use of phencyclidine may lead to aggressive behaviour accompanied by memory loss. Tolerance of the effects of phencyclidine occurs, although withdrawal symptoms are rare in humans. Animal studies suggest that dependence could occur in heavy users (Abraham, 2009).

Low doses of ketamine produce mood elevation, while at higher doses the user experiences sensory and perceptual distortions and out-of-body experiences similar to those reported with LSD. Frightening hallucinations, thought disorder, and confusion can also occur. These usually remit after a few hours. Patients who are admitted to hospital with ketamine intoxication show evidence of sympathetic overactivity, with chest pain, tachycardia, and palpitations. They may also experience nausea and vomiting, difficulty in breathing, ataxia, mutism, and temporary paralysis. Rarely, severe agitation and rhabdomyolysis can occur.

Treatment of intoxication. Treatment of acute phencycli-dine intoxication is symptomatic, according to the features listed above. Haloperidol, diazepam, or both may be given. Caution should be exercised if using benzodiazepines alone, because of the risk of further behavioural disinhibition. Chlorpromazine should be avoided, as it may increase the anticholinergic effects of phencyclidine and worsen the patient’s mental state. Hypertensive crisis should be treated with antihypertensive agents such as phentolamine. Respiratory function must be carefully monitored because excessive secretions may compromise the airway in an unconscious patient. Treatment of ketamine intoxication is also supportive and symptomatic. Antipsychotic drugs have little effect on the psychiatric symptoms, but benzodiazepines are reported to be helpful.

For reviews, see Abraham (2009) and Winstock and Schifano (2009).

Volatile substances (solvents, inhalants)

The misuse of volatile substances (also known as solvents) is not new, but public concern about widespread misuse first became apparent in the USA in the 1950s. Similar concerns emerged in the UK in the early 1970s. Although public interest has waned since then, there is a continuing high level of volatile substance misuse, particularly among adolescents. The pharmacological actions of volatile substances in the central nervous system are unclear but, like alcohol, they may increase the fluidity of neuronal cell membranes and could also increase brain GABA function (Beckstead et al., 2000).

Epidemiology. Volatile substance misuse is a worldwide problem. The Psychiatric Morbidity Survey (McManus et al., 2007) reported that in households in England the lifetime use of volatile substances was about 1.4%, with 0.1% of those surveyed reporting use in the last year. However, the survey did not include teenagers under the age of 16 years, among whom current use may be highest. Amyl nitrite(‘poppers’) appears to be more commonly used (see Table 17.8), but has a different pattern of use and is not discussed here. Volatile substance misuse is highly prevalent among the very young homeless populations in South American countries.

Volatile substance use occurs mainly in young men, and is more common in individuals from lower socioeconomic groups. Most of the young people who are known to use volatile substances do so as a group activity, and only about 5% are solitary users. There is some evidence that a subgroup of volatile substance users have antisocial personality disorder and are likely to use and misuse multiple substances. However, the epidemiological data suggest that most individuals who use volatile substances do so only a few times and then abandon the practice (Ives, 2009).

Substances used and methods of use. The volatile substances used are mainly solvents and adhesives (hence the name ‘glue sniffing’), but also include many other substances, such as petrol, cleaning fluid, aerosols of all kinds, agents used in fire extinguishers, and butane. Toluene and acetone are frequently used. In this chapter the term ‘volatile substance’ will be used to denote all of these various substances. The methods of ingestion depend on the substance, and include inhalation from the tops of bottles, beer cans, cloths held over the mouth, plastic bags, and sprays. Volatile substance use may be associated with the taking of other illicit drugs, or with tobacco or alcohol consumption, which can be heavy.

Clinical effects. The clinical effects of volatile substances are similar to those of alcohol. The central nervous system is first stimulated and then depressed. The stages of intoxication are similar to those of alcohol, namely euphoria, blurring of vision, slurring of speech, incoordination, staggering gait, nausea, vomiting, and coma. Compared with alcohol intoxication, volatile substance intoxication develops and wanes rapidly (within a few minutes, or up to 2 hours). There is early disorientation, and 40% of cases may develop hallucinations, which are mainly visual and often frightening. This combination of symptoms may lead to serious accidents.

Adverse effects. Volatile substance misuse has many severe adverse effects, of which the most serious is sudden death. These fatalities occur during acute intoxication, and about 100 such deaths occurred annually in the UK in the 1990s, although there has been a decline subsequently, with 36 deaths being recorded in 2008 (Ghodse et al., 2010). Around 50% of the deaths are due to the direct toxic effects of the volatile substance, particularly cardiac arrhythmias and respiratory depression. The rest are due to trauma, asphyxia (due to plastic bag over the head), or inhalation of stomach contents.

Chronic users may show evidence of neurotoxic effects, and severe and disabling peripheral neuropathy has been described in teenager misusers. Other neurological adverse effects, particularly associated with toluene, include impaired cerebellar function, encephalitis, and dementia. Volatile substance misuse can also damage other organs, including the liver, kidney, heart, and lungs. Gastrointestinal symptoms include nausea, vomiting, and haematemesis.

Tolerance and dependence. Dependence can develop if use is regular, but physical withdrawal symptoms are unusual. When such symptoms occur they usually consist of sleep disturbance, irritability, nausea, tachycardia, and, rarely, hallucinations and delusions. With sustained use over a period of 6 to 12 months, tolerance can develop.

Diagnosis. The diagnosis of acute volatile substance intoxication is suggested by several features, including glue on the hands, face, or clothes, a chemical smell on the breath, rapid onset and waning of intoxication, and disorientation in time and space. Chronic misuse is diagnosed mainly on the basis of an admitted history of habitual consumption, increasing tolerance, and dependence. A suggestive feature is a facial rash (‘glue-sniffer’s rash’) caused by repeated inhalation from a bag.

Treatment. As noted above, for many users experimentation with volatile substances is a temporary phase that does not appear to lead to persistent misuse or dependence. Advice and support may be sufficient for such individuals. However, a significant subgroup of those who misuse volatile substances also misuse other substances, such as alcohol and opioids. Such individuals are more likely to have an antisocial personality disorder and to have experienced a chaotic and abusive family life. Treatment of this group is difficult, and a full range of psychological and social treatments is likely to be needed (see above). There is no specific pharmacotherapy for volatile substance misuse, but associated psychiatric disorders such as depression may require treatment in their own right.

Prevention. Prevention of volatile substance misuse may best be directed at the large numbers of young people who experiment with volatile substances as a result of curiosity or peer pressure. Policies include the restriction of sales of volatile substances to children and adolescents. Education, particularly concerning the risk of severe injury and death (which can, of course, occur in occasional or first-time users), seems to be worthwhile. Wider social measures such as the provision of improved recreational facilities have also been advocated.

For a review of volatile substance misuse, see Ives (2009).

Further reading

Department of Health (2007). Drug Misuse and Dependence: UK guidelines on clinical management. Department of Health, London. (Current practice guidelines on the assessment and treatment of drug misuse.)

Gelder MG, López-Ibor JJ Jr, Andreasen NC and Geddes JR (eds) (2009). Section 4.27: Substance use disorders. In: The New Oxford Textbook of Psychiatry. Oxford University Press, Oxford.

National Institute for Health and Clinical Excellence (2011). Alcohol-Use Disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. Clinical Guideline 115. National Institute for Health and Clinical Excellence, London. (A periodically updated comprehensive review.)

Robson P. (2009). Forbidden Drugs. Oxford University Press, Oxford. (A very readable account of illegal drugs, the reasons for their use, and treatment of misuse.)