THE MYSTERY. Many medications have an effect on sleep. Drugs can have both good and bad effects on sleep. Many prescription and over-the-counter preparations, alcohol, and recreational drugs can play havoc with nighttime sleep or cause daytime sleepiness.
The Case of the Executive with Lifelong Insomnia
The patient had come to the sleep clinic because she had insomnia. She was a thirty-five-year-old lawyer working as an executive for a financial company. Her job performance had recently deteriorated, and she was concerned about making mistakes. Her insomnia had begun when she was a child, and her mother had told her she had always been a poor sleeper. She had learned to cope with her difficulty sleeping as a child and later as a student, doing well in school and college.
Then, about six months before she came to see me, her insomnia had worsened to the point where she had asked her doctor for sleeping pills. She had always resisted them in the past because she thought they were addictive. But after she started taking the pills, her insomnia became, if anything, worse than it had been. Her husband had started to complain that her sleeplessness and restlessness were causing him to lose sleep, and their bed was always a mess in the morning, with bedclothes kicked into a tangle.
A doctor’s most powerful tool is to ask questions. I was pretty sure I would be able to solve her problem with just a few.
What people consume or take into their bodies may make them sleepy or keep them from sleeping. It is important for us all to be aware of the sleep-related side effects of some of the more common drugs and of alcohol.
Drugs That Affect Sleep
Two-thirds of the U.S. adult population use prescription medications each month, at a total cost of about $300 billion. And according to a U.S. government report from 2015, 9.3 percent of males and 12 percent of females take five or more prescription medications each month. A side effect of many medications is sleep disturbance. There are literally hundreds of widely used medications and products likely to cause sleep problems, so I shall discuss only the most commonly used ones here.
Patients who are taking a medication that they suspect might be causing problems with their sleep can look up the product on the internet; product inserts, for example, can usually be found on the manufacturer’s website. Keywords such as insomnia, restlessness, sleepiness, fatigue, drowsiness, and somnolence should help them find other information. If the information is too technical, or if the problem seems to persist, the patient should discuss the issue with his or her doctor.
Antidepressants are the most commonly used drugs taken in the United States and by people referred to a sleep clinic. Each month 6 percent of all males and 11.8 percent of all females take antidepressants. Depression is a common cause of sleep disorders. But the antidepressants themselves can cause sleep symptoms, and some patients who have sleep disorders that cause sleepiness are incorrectly diagnosed as being depressed and prescribed antidepressants.
It is hardly surprising that antidepressants can have an effect on sleep: their main action affects certain chemicals in the brain, where sleep is controlled. Not all antidepressants, however, affect sleep in all patients. It is sometimes a challenge for the doctor and the patient to figure out which problems are related to the medication and which to the underlying depression, or whether both are causing the sleep problem.
For some people, certain antidepressants can cause sleepiness as a side effect. (Some doctors consider this a benefit.) But this side effect can be inconsistent from person to person: the same antidepressant can cause sleepiness in one patient and insomnia in others. Some patients might even have both side effects simultaneously—they might become very sleepy yet have difficulty falling asleep. These unwanted effects often lessen as treatment continues, as the patients become used to the medication and as the depression lifts. The doctor might change the timing of when drugs are taken to mitigate the side effects. If an antidepressant causes sleepiness, for example, the patient could start taking the drug at bedtime. If it is stimulating, the patient could try to take it at some time other than bedtime if possible. Patients should discuss their treatment schedule with their doctor.
Other drugs used to treat psychological and psychiatric conditions (see Chapter 16) can also affect sleep, so it is always safest to check with a doctor before taking them.
DRUGS USED FOR CARDIOVASCULAR DISEASE
Because cardiovascular diseases are common, medications used to treat these conditions are among the most widely used by the general population.
Drugs used to treat high blood pressure. Beta blockers (for example, propranolol [Inderal]) are used to treat diseases of the heart (including abnormal heart rhythms) and hypertension. In 2012, 7.3 percent of adult males and 9.1 percent of adult females in the United States took a beta blocker. These medications can cause nightmares and insomnia, though not all the drugs in this category have these effects. Some beta blockers not only affect the cardiovascular system, they make their way into the central nervous system, where they reduce the production of melatonin. Before taking a beta blocker, patients should consult with their doctor about its effect on sleep. Research published in 2012 showed that taking melatonin improved the disturbed sleep of people taking beta blockers.
Alpha-2 agonists (clonidine, methyldopa) can cause nightmares, insomnia, and daytime sleepiness. Calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors are used to treat high blood pressure; they very rarely cause problems with sleep. However, for some patients the ACE inhibitors can cause inflammation of the upper parts of the breathing passage, and this can lead to obstructive sleep apnea and severe, almost uncontrollable, coughing, which is likely to keep the patient awake at night. Such drugs usually have names that end with “-pril,” and examples include lisinopril, ramapril, and captopril. After the patient has stopped taking these medications, it may take one to four weeks for the symptoms to improve. (In rare cases the symptoms might persist for several months.) Since the patients still need to treat their high blood pressure, they are sometimes switched to angiotensin II receptor blockers, drugs whose names typically end in “-artan.” Examples include losartan and valsartan.
Cholesterol-lowering drugs. These drugs, called statins—such as rosuvastatin (Crestor), atorvastatin (Lipitor), pravastatin (Pravachol), and simvastatin (Zocor)—are used to lower blood cholesterol levels. These are among the most widely used medications and have few effects on sleep. Some patients have reported insomnia when taking these medications, though it is unknown why the drugs might have this effect.
Histamine is a chemical found in some specialized cells of the body. It is released from these cells during an allergic reaction. Histamine itself then interacts with receptors on other cells. There are two main types of histamine receptors (called histamine-1 and histamine-2) in the body. Histamine-1 receptors are found in the nervous system as well as in cells that are activated in an allergic reaction. The antihistamines that were commonly used until recently blocked these receptors, and their major side effect was to cause sleepiness. Diphenhydramine, an old medication, introduced in the mid-1940s, is used in several over-the-counter sleep medications. Similar medications introduced over twenty years ago include the ingredient triprolidine and azatadine and are usually available in North America in combination with pseudo ephedrine. People taking these combined medications may find that they have daytime sleepiness and insomnia.
The second-generation antihistamines do not have this side effect. The most widely used second-generation histamine-1 antagonists, cetirizine (Zyrtec in the United States and the United Kingdom, Reactine in Canada), fexofenadine (Allegra), and loratadine (Claritin), cause few symptoms related to sleep. The absence of these side effects perhaps explains why these types of antihistamines have become much more popular in recent years.
DRUGS USED TO REDUCE STOMACH ACID
Histamine-2 receptors are found in cells of the stomach lining. When activated they can cause overproduction of stomach acid. Histamine-2 receptor antagonists—for example, ranitidine (Zantac)—block this receptor directly and thus reduce the production of acid. Proton pump inhibitors such as omeprazole (Prilosec in the United States, Losec in Canada) and esomeprazole (Nexium) have a different effect on these cells, while reducing the production of acid. These widely used medications usually have little direct effect on sleep. However, iron and vitamin B12 are best absorbed when there is acid in the stomach; patients who use these drugs for a long period of time might experience a reduction in the absorption of iron or B12. This in turn can lead to iron or B12 deficiency, a cause of restless legs syndrome.
Pseudoephedrine and phenylpropanolamine are ingredients in medications that treat nasal congestion. These medications can sometimes cause insomnia. Phenylpropanolamine has been withdrawn from the market in both the United States and Canada because of concern that the product can cause stroke in rare instances.
Asthma itself can cause insomnia, particularly if the patient is short of breath, wheezes, or coughs at night, disrupting sleep. Most of the treatments currently available that involve puffers (bronchodilators or steroid medications) have little direct effect on sleep. However, patients who overuse over-the-counter bronchial dilator puffers that contain older medications such as epinephrine could experience difficulty in falling asleep, particularly as these medications are stimulants. Medications containing theophylline can also cause insomnia in asthmatics because this medication is chemically related to caffeine.
DRUGS USED TO TREAT PAIN AND JOINT DISEASES
Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used to relieve the pain of joint diseases, have no known effects on sleep. Examples include ibuprofen (Motrin or Advil), naproxen (Aleve), and celecoxib (Celebrex).
Narcotic painkillers such as codeine and morphine lead to drowsiness, but typically what ensues will be a light sleep with many awakenings. Morphine and drugs with morphine-like effects can suppress breathing. I have seen several patients with sleep apnea brought on by the use of morphine or methadone. The sleep apnea of these patients has been called complex apnea, a form of central apnea. These patients might have sleepiness related to both the medication and the apnea.
DRUGS USED TO TREAT NEUROLOGICAL CONDITIONS
Since the brain controls sleep, drugs used to treat diseases of the nervous system are likely to affect sleep. People receiving such medications should be warned about sleepiness as a possible side effect, and they should not drive if they experience this side effect.
Drugs used to treat Parkinson’s disease. As we saw in Chapter 15, Parkinson’s disease itself can cause sleep problems. The drugs used to treat the condition usually improve sleep and are used to treat restless legs syndrome. But sometimes the same drugs (those that imitate the effects of a chemical called dopamine) might cause the patient to become sleepy in the daytime. These drugs can also cause patients to develop problems with impulse control, leading to compulsive shopping, pathological gambling, or heightened sexual drive. Patients experiencing these symptoms should consult with their neurologist, who can switch them to other products.
Anti-epilepsy medications. There are a very large number of drugs available to treat epilepsy, and some are also used to treat headaches, fibromyalgia, and restless legs syndrome. Most can cause sleepiness in the daytime. Epilepsy must be treated, and unfortunately the patient might have to tolerate the sleepiness in order to control the seizures.
DRUGS USED TO TREAT CANCER
There are many chemotherapy medications used for different types of cancer. I cannot review them in any detail here, but a few points are worth mentioning. Many chemotherapy medications have nausea and vomiting as side effects that can impact sleep. Some of the drugs can also affect the nervous system, and some users develop restlessness and restless legs syndrome. Many people on chemotherapy experience overwhelming fatigue.
About 80 percent of breast cancer cells are estrogen-receptor positive, which means that estrogen stimulates breast cancer cells to grow. Several medications which counteract this effect on these cancer cells are now widely used as additional treatment for breast cancer after surgery and as a breast cancer preventative. There are three types of such hormonal medications:
SERMs (selective estrogen-receptor modulators): tamoxifen (Nolvadex, Valodex, and Istubal), raloxifene (Evista), and toremifene (Fareston);
Aromatase inhibitors: anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara); and
ERDs (estrogen-receptor downregulators): fulvestrant (Faslodex).
The anti-estrogen effect of these medications frequently causes menopause symptoms, including hot flashes and night sweats, which can result in sleeplessness. (These problems are discussed in Chapter 5.)
Many people use alcohol as a sleep aid. This is ill advised. Although alcohol does make a person drowsy, when the blood alcohol level drops, it activates the sympathetic nervous system, which wakes the person up, speeds up the heart, and might cause sweating and headaches. People should probably not try to sleep until after the alcohol has disappeared from the body to avoid this effect. Roughly one ounce of alcohol is found in two 12-ounce servings of regular beer (usually about 5 percent alcohol), two 5-ounce servings of wine (usually about 12 percent alcohol), and two 1.5-ounce servings of distilled spirits (usually about 40 percent alcohol; some distilled spirits have much higher concentrations), and it takes the body about an hour to clear an ounce of alcohol.
Another negative side effect of alcohol is that it can make some people snore. For some people, for example those with sleep apnea (see Chapter 12), the sleep-breathing problem becomes much worse after alcohol consumption. Hundreds of women have told me that their husband’s snoring is worse after he has had a few drinks. When the snorer wakes up with a hangover or severe headache, it might be because of apnea. Alcohol makes people sleepy, and the combination of the alcohol and sleep deprivation or a medication that normally makes the user sleepy can cause the user to pass out. Alcohol use increases sleepwalking in those who have a tendency toward this type of nocturnal wandering. Alcohol is a nervous system depressant, and it can worsen the symptoms of depression.
Drug and Alcohol Abuse
Not all the possible drug abuse problems can be covered here. I shall address only the most common ones. Most important for people taking drugs or alcohol to keep in mind is that all drugs that affect the brain can affect sleep. These include alcohol, caffeine, prescription drugs, illegal drugs such as cocaine, amphetamines, and many others.
Abuse of prescription drugs. Some prescription drugs can be addictive. This is true of narcotic painkillers and is sometimes the case with pills used to treat anxiety and insomnia. Often a patient is not truly addicted but is psychologically dependent on a drug, such as a sleeping pill. Patients taking these drugs should consult with their doctor about ways to avoid becoming dependent on them. (I discuss how to reduce sleeping pill dependence in Chapter 19.)
Alcohol abuse. Alcoholics have many problems with sleep. They may have trouble falling or staying asleep, have episodes of sleepwalking, and be very sleepy in the daytime. When binge drinking, they might drink, then have a short sleep, then drink again, in an ongoing cycle. Many recovering alcoholics find that their sleep does not return to normal. They may continue to have severe difficulty in falling and staying asleep, and might benefit from seeing a sleep specialist.
Illegal drugs. Almost all illegal drugs have an effect on the nervous system and can lead to sleeplessness or sleepiness. A big change in personality and sleep pattern often signifies either a psychiatric problem or a drug problem. Both of these are beyond the scope of this book, and people using them should consult with a doctor.
Club drugs. Just as alcohol was widely available during Prohibition, illegal drugs that affect the nervous system are widely available today, and are mainly used by teenagers and young adults. These compounds, often categorized as club drugs, are taken at bars and dance parties, such as raves, that can last all night. Parents should be aware of the dangers of such drugs to their children. Over 20 percent of high school students have attended a rave where club drugs are available, according to a study from 2015. The National Institute of Drug Abuse posts useful information about current club drugs, including descriptions of their effects and prevalence among certain age groups, on its website (drugabuse.gov).
Stimulants (uppers) such as MDMA (also called ecstasy) are commonly used by students. In the United States about one in ten high school seniors admits to having used it. More than 3 percent admit to having used it at some point in the previous month. Used to increase stamina, in large doses MDMA can cause body temperature to become so high that it can lead to muscle breakdown as well as kidney and cardiovascular system failure. It can lead to heart attacks, strokes, seizures, and death. MDMA can permanently damage brain cells. Insomnia, which can be severe, is common with this drug, and can continue after the person stops using it. Amphetamines, cocaine, and illegally prescribed Ritalin can all cause insomnia.
Depressants (downers) such as rohypnol (flunitrazepam, a medication related to Valium but not approved in the United States), LSD (lysergic acid diethylamide, a hallucinogen), GHB (gamma hydroxybutyrate, also called sodium oxybate, Xyrem), opiates (for example, heroin), and ketamine (an anesthetic) are other popular club drugs, sometimes used to counter the stimulant effects of uppers. Some of these drugs make people pass out and have been used as so-called date-rape drugs. In my experience Xyrem is not a problem for the latter, because it is hard to get (a highly controlled pharmacy controls it for the entire country) and salt is added to it so that people taking it can recognize it. However, GHB can be manufactured easily, and this illegal product is what finds its way into clubs. Without the added salt this product is tasteless, and a person taking it will fall into a deep sleep within minutes.
Back to the Executive with Lifelong Insomnia
The question that started my patient and me down the right path was “What sleeping pill were you prescribed?” She named the medication. It was not a sleeping pill but an antidepressant that she was taking at bedtime. She did not know that she was taking an antidepressant or that a side effect of the medication was to make her more fidgety at bedtime; in fact, she had developed restless legs syndrome, which was what kept her husband awake at night. Before she began taking the “sleeping pills” she had lain in bed calmly waiting for sleep. She now tossed and turned all night. She continued to take the pills because she assumed that her insomnia was getting worse. She had not made the connection between taking the pills and the increase in her symptoms.
The patient had primary insomnia (insomnia whose cause is still a mystery), which she had had most of her life. We discussed treatment options for her. She felt she had to use sleeping pills some nights in order to function at work the next day. We picked one of the new short-acting sleeping pills. A few weeks later she called me to tell me that her restlessness had vanished a couple of days after she stopped taking the antidepressant. She was getting excellent sleep on the new sleeping pill, with absolutely no side effects. She was taking the pills three or four nights a week and was satisfied.
Drugs can affect sleep, and people planning to use medications, whether produced by pharmaceutical companies or available in health food stores, should inform themselves about what they are taking before they do so. Why are they taking the drug? To cure a disease? Has a doctor diagnosed the problem? Are they receiving the right treatment? What are the side effects of the medication? It is important for people to consult with their doctor about all the effects of a particular drug, including its effect on sleep, before putting it in their bodies.