The ASAM Principles of Addiction Medicine 5th Edition

90. Co-Occurring Personality Disorders and Addiction

Stephen Ross, MD, Jeffrey R. Guss, MD, and Erin Zerbo, MD








Personality disorders (PDs) are defined by the DSM-IV-TR as “enduring patterns of inner experience and behavior” that are deep seated, inflexible, and at odds with cultural norms and expectations and produce psychopathologic symptoms affecting cognition, emotion, interpersonal functioning, and impulse regulation (1). The patterns cause repeated conflicts with one’s social and occupational environment and lead to emotional distress, while the individual usually experiences the disorder as ego-syntonic and externalizes blame for his or her dysfunction. The onset of PDs is in late adolescence or early adulthood when personality trait patterns become stable (1). Although PDs tend to have a chronic course of illness, longitudinal studies have generally supported the notion that PDs tend to improve over time from the perspective of decreases in clinical symptomatology, although the evidence is more mixed for cluster A and C disorders (26).

PDs and substance use disorders (SUDs) are highly associated with each other, especially in mental health and substance abuse treatment settings where they represent the norm in terms of comorbidity (7,8). Screening and the use of standardized assessment instruments are vital components of diagnostic formulation to determine the presence of a PD that is distinguishable from or co-occurring with an SUD. Given the epidemiologic data where the majority of patients with a PD have a co-occurring addictive disorder and vice versa (7), an a priori assumption diagnostically should be that there are two separate problems until proven otherwise. Patients with co-occurring SUDs and PDs can benefit from treatment as much as those without PDs, but the presence of a PD does negatively affect the course of treatment of the addictive disorder and is associated with worse outcomes (9). It is important to provide comprehensive care, optimally within a structured environment with a dual focus (i.e., PD and SUD), utilizing integrated psychosocial treatments for PDs and SUDs, in an integrated system of care, and providing symptom-targeted pharmacotherapy when appropriate as an adjunct to psychosocial interventions. This chapter reviews the following regarding PDs and co-occurring SUDs: definitions/classification systems, epidemiology, diagnostic assessment (theoretical and practical), and treatment (outcomes, psychosocial, pharmacologic).


DSM-IV Categorical Approach

The DSM-IV employs a categorical classification system placing the PDs into three clusters based on symptom similarities (A, B, and C) that produces 10 distinct disorders:

■  Cluster A (paranoid, schizoid, schizotypal): These disorders are characterized by odd or eccentric cognition and behavior related to the schizophrenia spectrum (10).

■  Cluster B (antisocial, borderline, histrionic, narcissistic): These disorders are marked by emotional, dramatic, or erratic behavior and are related to trait impulsivity and/or affect dysregulation and are on the spectrum with impulse disorders (11).

■  Cluster C (avoidant, dependent, obsessive–compulsive): These disorders are marked by anxious symptoms, are related to trait anxiety or compulsivity, and are on the spectrum with anxiety disorders (12).

This categorical or typologic system is based on a variety of theoretical perspectives including psychoanalytic theory, classical phenomenology, and social learning theory (13). It includes a list of symptoms with diagnoses made if a threshold or cutoff level of a given number of diagnostic criteria is present.

Dimensional Considerations: Factor Models of Personality Structure

Another prominent diagnostic model with considerable empirical support within the PD field is the dimensional approach to personality and personality psychopathology. In this model, there are a continuous spectrum and normal distribution of basic personality traits within a given population, and personality psychopathology occurs at the extreme ends of this spectrum (14). PDs are conceptualized as quantitatively, rather than qualitatively, different from normal personality (15).

There are a number of dimensional models that have been theorized and empirically studied. In the 1960s, Eysenck (16,17) developed a model of higher-order dimensions of personality traits: neuroticism and extraversion, dubbed the “Big Two,” the most extensively researched and validated of the dimensional models (14). Neuroticism describes a tendency toward intrapsychic distress, negative emotions, and poor coping with stress, while extraversion includes positive emotionality, energy, and interpersonal style. Eysenck later added a third behavioral dimensional construct of disinhibition versus constraint to create the “Big Three.” In the last 20 years, there has been a general consensus in the Five-Factor Model (FFM; nicknamed “Big Five”), which demarcates five superordinate or higher-order personality domains: neuroticism, extraversion, openness, agreeableness, and conscientiousness (18,19). It is most commonly assessed using the NEO Personality Inventory (20). The FFM contains neuroticism and extraversion from the Big Two, while agreeableness (tendency for empathy, trust, mutuality) and conscientiousness (tendency toward organization and self-discipline) correspond to low disinhibition/high constraint. Opennessincludes a range of interconnected traits that includes aesthetic sensitivity and the tendency to enjoy creativity or culture, fantasy and imagination, an affective attunement in oneself or others, and permeability to new ideas and experiences (21); it is correlated with creativity (22) and cognitive ability (23) and has the lowest association with psychopathology compared to the other four FFM domains (24).

The FFM has been extensively studied including meta-analyses, is applicable cross-culturally (25,26), and demonstrates convergent and discriminant validity (27) as well as temporal stability in community (28,29) and clinical samples (30,31). Hundreds of studies have examined the relationship between measures on the FFM and psychopathology, including DSM PD symptoms (14,32). In general, high neuroticism, low agreeableness, low conscientiousness, and low extraversion are associated with most PDs (33,34), and each PD has a unique profile on the FFM. An exception to the general pattern of elevated intrapsychic distress (i.e., neuroticism) in PDs is the psychopathy component seen in antisocial personality disorder (ASPD), which is characterized by low neuroticism, disinhibition, impulsivity, low agreeableness (i.e., interpersonal antagonism), sensation seeking (elevated extraversion), and deficits in empathy (low levels of warmth component of extraversion) (35).

Using the FFM, SUDs generally exhibit the following profile: high neuroticism, low conscientiousness, higher disinhibition, higher extraversion, and lower agreeableness (36). While the FFM has expanded the number of domains to five, its structure can still be collapsed back into two primary domains: behavioral undercontrol (extraversion + disinhibition) and neuroticism (i.e., negative emotionality). Behavioral undercontrol includes lack of constraint, sensation seeking, high risk taking, novelty seeking, impulsivity, and low conscientiousness. Although both behavioral under-control and negative emotionality have been correlated with SUDs, behavioral undercontrol has stronger evidence that it is a positive predictor of SUDs (see Etiologic Models section for a more detailed discussion) (37).

Changes from the DSM-IV to DSM-5 PD Classification System

The DSM-IV classification system for PDs was based on phenomenology and clinical observation and has been criticized as leading to high comorbidity between Axis II PDs, vaguely defining core commonalities among PDs and not accounting for the level of personality dysfunction or the complexity and individual manifestations of personality psychopathology (38). To address these shortcomings, the DSM-5 has proposed a new classification system, considered a “hybrid” categorical–dimensional system that includes (a) common diagnostic criteria, impairments in self (identify vs. self-direction) versus interpersonal(intimacy or empathy); (b) five levels of personality function that account for severity variability and generate 60 possible combinations of self versus interpersonal functioning; (c) a dimensional system with five domains (negative affectivity, detachment, antagonism, disinhibition, psychoticism) comprising 25 pathologic personality traits; and (d) a categorical system with 6 of the 10 DSM-IV diagnoses (schizotypal, borderline, narcissistic, antisocial, avoidance, obsessive–compulsive) remaining although the methodology to diagnose them will be changed relative to the DSM-IV.


PDs and SUDs are both prevalent in the general population. In looking at five well-designed (i.e., use of DSM-IIIR, DSM-IV, or ICD-10 diagnostic criteria and structured or semistructured interviews) community surveys of PDs published since 2000 with sample sizes ranging from 214 (39) to 43,093 (40), the estimated prevalence of any PD in the general population ranged from 4.4% to 13.4% with a median of 9.6% and with cluster C disorders (obsessive–compulsive personality disorder [OCPD] and avoidant PD) being the most commonly diagnosed (41). In comparison, SUDs, defined as either substance abuse or substance dependence, affect approximately 22.6 million (9.2% of the population) individuals 12 years of age or older, including both alcohol or illicit drugs (42). This does not include nicotine use disorders, which affect approximately 21% of the population (43).

In addition to both being prevalent conditions by themselves in the general population, PDs and SUDs are intimately related in community samples. For instance, in a nonpatient sample of approximately 800 individuals who were relatives of both normals and psychiatric patients, of those who had any PD, 43% and 53%, respectively, met the criteria for a lifetime alcohol use disorder (AUD) or drug use disorder (DUD), and having a PD increased the risk of both AUD and DUD by a factor of four compared to individuals without a PD (44). Using revised diagnostic criteria from the NESARC community sample, Trull et al. (8) found that each PD was strongly associated with lifetime dependence syndromes with the highest rates of co-occurrence as follows: alcohol dependence co-occurring with ASPD, borderline personality disorder (BPD), and histrionic personality disorder (HPD), all at approximately 50%; drug dependence co-occurring with HPD 29%, dependent PD 27%, and ASPD approximately 25%; and nicotine dependence co-occurring with ASPD, BPD, and dependent PD, all at approximately 50%.

Compared to the rates of PDs in community samples, the rates of PDs in psychiatric and substance abuse disorders are significantly increased (7,44). In selecting well-designed studies (i.e., random selection, sample size ≥100, use of standardized diagnostic instruments), Verheul (7) reported on the prevalence rates of Axis II psychopathology: 45% to 80% (median 60%) in psychiatric patients and 35% to 73% (median 57%) in patients treated for SUDs (30).

Even though cluster C diagnoses (OCPD, avoidant PD) are the most common PD diagnoses in the general population, cluster B disorders (ASPD and BPD) are the most commonly associated with SUDs either in community or in treatment (substance abuse or psychiatric) samples. In a review of comorbidity data between BPD and SUD, Trull et al. (45) reported that among those seeking addiction treatments, rates of BPD ranged from 5% to 65%, and conversely, among those receiving treatment for BPD, the prevalence of current SUDs is between 25% and 67%. From the Epidemiological Catchment Area (ECA) study, ASPD (among men) was more frequently diagnosed with an SUD than any other Axis I or II disorder with 83% of individuals with ASPD also meeting the criteria for an SUD and with ASPD being diagnosed in 18% of those with a DUD and 14% with an AUD (46).

In addition to PDs co-occurring with Axis I SUDs, they also commonly co-occur with other non-SUD Axis I disorders. Patients with PD diagnoses, who present for treatment, have an average of approximately three co-occurring Axis I disorders (47,48).


Before discussing the practical aspects of clinical diagnostic assessments for patients with co-occurring PDs and addictive illnesses, a brief discussion of the etiologic theories of these disorders is in order as well as any evidence that supports a particular model. Given the markedly high co-occurrence of SUDs and PDs (especially ASPD and BPD), a correlation between the two has long been assumed, theorized, and studied with the evidence for an association derived from genetic, epidemiologic, retrospective, and longitudinal studies (49). In addition to a discussion about the etiology of PDs, two main classification systems for PDs comorbid with SUDs will be discussed: co-occurring and etiologic.

Etiology of PDs

PDs are thought to arise from an interaction between biologic (genes, temperament), psychological, familial, and sociocultural risk factors over time, with the risk increasing with the number of risk factors involved. Temperament is an individual’s biologically determined innate disposition or pattern of thinking, feeling, and behaving and accounts for the majority of variance in personality traits (50). The biologic basis of temperament is supported by animal and human studies with parallels seen in temperament structure (i.e., defensive reactions to fear and anger, approach reactions of activity and pleasure to high intensity stimulation, attention and orienting) (14,51). There is no simple relationship between single genes and temperament, and it is likely that temperament is polygenetically determined (52). Personality traitsare defined as individual variation in behavior, cognition, and affect that are stable over time and represent a combination of temperament and longitudinal experience (53). In dimensional models of personality psychopathology (see Dimensional Considerations), PDs represent an amplification and psychopathological expression of normative personality traits leading to functional impairment (15). Both personality traits (5456) and PDs have a genetic, heritable component with twin studies demonstrating the heritability of PDs ranging from approximately 40% (for cluster A disorders) to approximately 60% (for cluster B and C disorders) (57). Longitudinal studies have demonstrated a considerable link between temperament, adult personality, and personality psychopathology (58).

Co-Occurring Models

In co-occurring models, there is the presence of two distinct disorders, one psychiatric and one addiction related. One possibility is that both disorders have their own unique independent etiologic determinants (biologic and environmental) and that both disorders happen to co-occur randomly without a common set of etiologic factors. In contrast, in the common factor type of co-occurring model, the co-occurrence of both a PD and an SUD is caused by shared vulnerabilities or risk factors, ranging from genetic to sociocultural, of both disorders. This model would be most applicable to the interaction between addiction and ASPD and BPD because of the considerable comorbidity as mentioned above. This model is best evaluated by twin, family, and adoption studies. From a genetic perspective, it is salient to know if genetic susceptibility to one disorder increases the risk to another. If shared genetic risk factors to both a PD and addiction were to account for the increased comorbidity, an elevated incidence of one disorder (i.e., SUD) would be expected in relatives of individuals with the other disorder (i.e., PD). However, there is little evidence to support this model other than some data suggesting common genetic influences on the personality dimension of behavioral dyscontrol/impulsivity that accounts for a significant genetic etiology for both alcohol dependence and conduct disorder/ASPD (5961).

Etiologic Models

Etiologic diagnoses come in two varieties: secondary SUD and secondary psychopathological models. In the secondary SUD models, the presence of a PD or pathologic personality traits are risk factors contributing to the development of an addictive spectrum disorder. Since the traits within a PD usually have some early manifestations in childhood and adolescence, it is possible to examine, prospectively, the relationship between maladaptive traits, seen prior to exposure to addictive substances, and the subsequent development of addiction. A number of traits have been identified that appear commonly in both SUDs and PDs (such as sensation seeking, novelty seeking, impulsivity, negative emotionality), and prospective studies with such traits identified in children or adolescents can assess for correlation with later onset of SUDs.

Several pathways have been proposed that might explain how certain personality traits or symptoms of a particular PD might lead to addiction (59). In all of these models, substance initiation and continued use in response to the personality psychopathology eventually translate into independent SUDs over a long enough period of time, typically with poor or no treatment for the psychiatric condition, whereby the neurobiology of the normative reward system can be sufficiently hijacked and corrupted leading to chronic neuroadaptive changes associated with the transition from substance misuse to abuse to dependence (62). Once dependence syndromes have developed, even if the original offending psychiatric condition (i.e., PD) is treated with remission of illness, the SUD is now established and can continue independent of its original relationship to the mental disorder causing it, effectively untethered. Of course, there will remain negative bidirectional effects now that there are two distinct problems:

(a) Behavioral disinhibition pathway: In this pathway, traits such as impulsivity, behavioral undercontrol, aggression, and diminished conscientiousness predict substance initiation and use syndromes presumably mediated through affiliation with deviant peer groups and poor socialization (63,64), consistent with ASPD and possibly BPD. Evidence for this comes from epidemiologic studies that demonstrate a strong link between SUDs and Axis I and II disorders along the impulsive spectrum, longitudinal studies that demonstrate a link between the above-mentioned antisocial traits that predates and predicts the development of an SUD in adolescents and young adults (6569) and is associated with earlier onset of initiation of substance use, earlier onset of SUDs, and a more severe form of the illness (70). The high rates of co-occurrence between ASPD and SUDs have led some authors to propose an “externalizing dimension” of psychopathology, which would include both ASPD and SUD and where both disorders would theoretically share the following dimensional personality traits: disinhibition (low agreeableness and low conscientiousness) and elevated sensation seeking and impulsivity (63,71). In a meta-analysis examining the FFM characteristics of externalizing disorders that analyzed 63 samples (N = 15,331) cross-sectionally for three groups (ASPD, SUD alone, co-occurring ASPD/ SUD), all three groups demonstrated similar levels of disinhibition (low levels of agreeableness and conscientiousness) and high levels of impulsivity (72).

(b) Stress reduction pathway: In this pathway, individuals with high neuroticism traits (i.e., stress sensitivity, negative emotionality, mood instability) can be predicted to develop an SUD as a way to attempt to self-treat these unpleasant affective and cognitive states. Khantzian’s “self-medication hypothesis” (SMH) is an example of a stress reduction pathway and views preexisting difficulties in self-esteem regulation, modulation of dysphoric affect, and self-care as establishing a vulnerability to the development of an SUD (73,74). The data supporting the SMH in general are mixed. Despite some studies from treatment samples suggesting specificity between a particular substance being used for a particular mental illness (7577), the majority of the data across a broad spectrum of mental illnesses do not reveal a strong relationship between type of mental illness and type of substance (78). However, there is evidence that patients may use substances of abuse to medicate unpleasant affective (i.e., dysphoric affect) states, across a variety of diagnoses, in a less specific way, to alleviate the dysphoria (79). This construct makes more sense when considering substance abuse rather than dependence, in which the use of substances over shorter periods of time can alleviate psychic distress before use progresses to having less and less psychological utility, and tends to ultimately worsen psychiatric symptoms. Several longitudinal studies have shown that high neuroticism traits in children are predictive of SUDs in adolescence and young adulthood (64,65,80,81) and might explain the comorbidity of SUDs seen in avoidant and BPD (49).

(c) Reward sensitivity pathway: This pathway suggests that individuals who show traits of novelty seeking, reward seeking, and extraversion are at increased risk for developing an SUD. The mechanism hypothesizes that these individuals experience an exaggerated reward response with addictive substances, which leads to a sensitization process, further reinforcing the addictive behavior. Some evidence from longitudinal studies supports this model (64,65,67,82), and it might account for the co-occurrence of SUDs seen in narcissistic, histrionic, and antisocial PDs (49).

In the secondary psychopathology model, substance abuse precedes and causes personality psychopathology. To accurately ascertain whether a given PD is caused by a particular drug, it is key to entertain multiple factors: the pharmacologic nature of the drug (i.e., stimulant, depressive, psychotogenic), the relationship to intoxication and withdrawal syndromes, dose, route of administration, amount and length of use, and whether there is any underlying personality pathology that is being exacerbated by the drug. A key question is to consider how long a given drug (related to either intoxication or withdrawal) can cause PD symptoms without having to consider a separate PD where a co-occurring diagnostic model more fits the clinical situation. It is a frequent clinical observation that active addiction generates significant characterologic symptoms that can often be indistinguishable from the symptoms of a PD (see Substance-Induced PD Symptoms). An example of this would be pseudopsychopathy, symptoms consistent with antisocial PD occasioned by drug use. Certain drugs of abuse (i.e., IV heroin, crack cocaine), especially those that are illegal and perceived as very harmful, are associated with such antisocial behaviors. These apparent symptoms of personality psychopathology should remit with sobriety without a preexisting PD. However, in this model, it is postulated that the ongoing substance abuse would be sufficient to permanently occasion a new and enduring pattern of personality psychopathology that would not have developed if the individual had never used/abused substances. There is little to no evidence from the literature that supports this model (59).

However, in a recent novel experiment, MacLean et al. (83) examined the relationship between psilocybin dosing sessions (with volunteers receiving anywhere from 2 to 5 dosing sessions) in a cohort of 52 normal participants, with consecutive sessions separated by at least 3 weeks, and longer-term (14-month follow-up) changes in personality dimensional measures. In this study, the NEO Personality Inventory was assessed at screening, 1 to 2 months after each drug session, and at 14 months after the last drug session. Of the FFM subscales, the opennessdomain significantly changed, both acutely and in a sustained manner. Furthermore, increased scores of mystical states of consciousness were positively correlated with increased openness, and those who had “complete” mystical experiences had enduring changes in openness up to 14 months postdosing. This study was a landmark in the field of personality research as it was the first study to demonstrate that it is possible to pharmacologically change a core aspect of personality through an experimentally mediated discrete event, presumably mediated by a profound spiritually oriented shift in consciousness.


Screening is a crucial step prior to diagnostic formulation. Since patients with PDs tend to have more severe pathology and more frequent treatment contact, they are more likely to present in the situations with the least time for assessment, such as emergency rooms or incarcerated settings (84,85). However, most screening questionnaires focus on specific PDs or require too much time to be used in routine clinical practice. To remedy this, Cloninger (86) has proposed a 20-item screen that focuses on four core features that are suggestive of any PD: low self-directedness, low cooperativeness, low affective stability, and low self-transcendence (the last encompassing unstable self-image, emptiness, and erratic world view). Clinicians can keep these features in mind as “red flags” for the need to pursue more thorough PD assessment.

The use of standardized assessment instruments is important in diagnosing PDs because traditional unstructured clinical diagnostic interviews are poorly reliable and are associated with missed and incorrect diagnoses (8789); there are a number of formal assessment tools used in evaluating personality pathology, although they were not specifically designed for an SUD population. The ones mentioned in this section demonstrate good reliability and validity from research. These tools range from self-report questionnaires to semistructured and structured diagnostic interviews. Self-report questionnaires that offer a comprehensive assessment of PDs from the DSM perspective include the Millon Clinical Multiaxial Inventory III (MCMI-III) (90) (perhaps the most widely used in research and clinical practice), the Personality Diagnostic Questionnaire-4 (91), the Minnesota Multiphasic Personality Inventory (MMPI) Personality Disorder Scales (92), and the Coolidge Axis II Inventory (CATI) (93), although the MMPI and the CATI are not specifically coordinated with the DSM-IV. Other self-administered questionnaires are more specific for particular PDs, such as the Psychopathic Personality Inventory (94), the Narcissistic Personality Inventory (95), and the Schizotypal Personality Questionnaire (96). Although self-report questionnaires assessing PDs have the advantage of being highly sensitive and therefore useful as screening tools, they have the disadvantage of a significant false-positive rate leading to overdiagnoses of PDs (97). This effect may be pronounced for an SUD population, since the questionnaires do not differentiate the effects of substance use from personality traits. Clinical interviews are important here to determine if a particular behavior is substance related or more global. Examples of clinician-administered diagnostic interviews, specifically designed for the DSM-IV, include the Diagnostic Interview for DSM-IV Personality Disorders (98), the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) (99), and the Structured Interview for DSM-IV Personality Disorders (100). Such assessments are useful to formally establish DSM-IV diagnoses but can be labor intensive and time consuming to administer, diminishing their feasibility and utility in routine clinical settings.

Any assessment tool must be considered along with other information sources, such as unstructured patient interview, collateral information, and longitudinal assessment. Collateral contacts can be helpful in elucidating long-standing behavior patterns, they can provide information that the patient is not able or willing to provide, and they can increase the convergent validity of diagnoses (101). Risk assessment for suicidality, self-injury, and violence deserves special attention, especially in patients with BPD and ASPD (102). Given the high-risk nature of these patients, a team-based approach and access to referral services is ideal for optimal management.

In addition to a careful substance history and risk assessment, important areas of focus include a history of trauma (abuse, neglect, conflict in the household), familial history of personality dysfunction, and quality/quantity of current and past interpersonal relationships. Inflexible or maladaptive coping skills are the hallmark of a PD. Close attention to interpersonal style and transference/countertransference can yield important diagnostic information. For example, patients with BPD tend to develop transference quickly and intensely and to have extreme and rapid oscillations (the clinician is experienced as all good and ideal and then suddenly all bad and malicious after a seemingly small disappointment). Schizoid or avoidant patients may be especially deferential or reserved in a clinical encounter. It is also important to rule out other co-occurring Axis I disorders whose symptom presentation may mimic symptoms of various PDs. For example, bipolar I or II disorder should be excluded before diagnosing BPD, and social phobia should be ruled out before diagnosing avoidant PD. A detailed temporal history and longitudinal observation and assessment are key to differentiate acute-state phenomenon usually associated with Axis I disorders (i.e., acute mood instability associated with mania) versus longer-term traits associated with PDs.

The ultimate goal of assessment is to determine the presence of a PD that is distinguishable from or co-occurring with an SUD. Several factors can help in this process (see Table 90-1). Given the epidemiologic data where the majority of patients with a PD (especially BPD and ASPD) have a co-occurring addictive disorders and vice versa, an a priori assumption diagnostically should be that there are two separate problems until proven otherwise by a process of exclusion (i.e., that it is a case of an etiologic diagnosis). As a general clinical rule, symptoms that persist beyond 1 month of abstinence are more likely to be primary. It is further important to assess substances of abuse and medical conditions that can occasion symptoms that mimic those of PDs or exacerbate them.



From American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association, 2000; Jang KL, Livesley WJ, Vernon PA, et al. Heritability of personality disorder traits: a twin study. Acta Psychiatr Scand 1996;94:438–444; Widiger TA. The DSM-III-R categorical personality disorder diagnoses: a critique and an alternative. Psychol Inq 1993;4:75–90; Ross S. The mentally ill substance abuser. In: Galanter M, Kleber M, eds. Textbook of substance abuse treatment, 4th ed. Washington, DC: The American Psychiatric Publishing, 2008:537–554, Ref. (103).

Substance-Induced PD Symptoms

Substances can mimic a wide variety of personality phenomenology and pathology along a temporal spectrum from acute to chronic. From a diagnostic perspective, it is important to know these effects to take into account when considering etiologic (i.e., secondary psychopathology) versus co-occurring diagnostic models. Below are salient examples, as categorized by DSM-IV PD clusters A, B, and C.

Cluster A

Consider psychotogenic substances. These include NMDA antagonists (e.g., PCP, ketamine, dextromethorphan, nitrous oxide), 5HT2 agonists (e.g., LSD, DMT), kappa opioid agonists (e.g., salvia divinorum), stimulants (e.g., cocaine, methamphetamines, substituted cathinones [i.e., mephedrone, “bath salts”]), CB1 agonists (e.g., cannabis, synthetic cannabinoids), inhalants (e.g., nitrous oxide, toluene), and chronic heavy alcohol use. Heavy methamphetamine or PCP use can occasion psychotic states that last for weeks to months even in the absence of underlying psychotic spectrum illnesses, including affective psychoses (104,105), and could be incorrectly diagnosed as schizotypal or paranoid PD. Of all substances, alcohol is the most psychotogenic and can cause chronic psychotic disorders (i.e., alcoholic hallucinosis, Korsakoff syndrome, Marchiafava-Bignami syndrome). This chronic psychotic state could appear like the new onset of cluster A symptoms especially if the psychotic symptoms were attenuated (105).

Cluster B

The affective instability of BPD can be mimicked by the intoxication and/or withdrawal states of many substances. Interpersonal difficulties, impulsivity, transient paranoia, and identity disturbance are all features that can be seen in patients with active addiction. One should be especially cautious of diagnosing ASPD during states of active drug use, since patients can be manipulative or resort to criminal activity to maintain their addiction. If there is no history of conduct disorder or criminal activity prior to the onset of SUD, pseudopsychopathy is the more likely diagnosis.

Cluster C

Consider anxiogenic substances, such as stimulants, CB1 agonists, and the serotonergic hallucinogens (i.e., LSD), especially when used in uncontrolled settings. While alcohol and opioids are both acute-acting anxiolytics, chronic use can lead to marked anxiety during periods of withdrawal, and protracted withdrawal can last for months (106).

Medically Induced PD Symptoms

In addition to drugs of abuse, there are other general medical conditions that can sufficiently alter physiologic brain processes to produce changes in personality, either acutely or over a longer period of time. Examples of conditions than can cause acute changes in personality include infections (i.e., herpes encephalitis, meningitis, sepsis), hematomas (i.e., epidural, subdural), and metabolic syndromes (i.e., hyperglycemia, hyperthyroidism, hypoxia, hypercarbia). Examples of medical conditions that can occasion longer-term changes in personality include frontal lobe traumatic brain injury (i.e., Phineas Gage), dementing syndromes (i.e., Pick’s, Alzheimer’s, Huntington’s, Wilson’s), infectious illness (i.e., Creutzfeldt-Jakob disease), CNS tumors (i.e., frontal lobe, pituitary), strokes, porphyrias, and chronic temporal lobe epilepsy. Traumatic brain injury predominantly damages frontal and temporal brain regions irrespective of etiology such as hemorrhages, contusions, or diffuse axonal injury (107). One of the most common effects of frontal lobe damage can be dramatic changes in personality and behavior. At least three major syndromes have been identified depending on the specific frontal cortical area damaged: medial frontal regions (including anterior cingulate and superior medial frontal regions) resulting in “pseudodepression” marked by avolition, lethargy, anhedonia, and delays in cognitive processing speed; orbito-frontal cortexleading to “pseudopsychopathy” marked by aggression, disinhibition, impulsivity, lack of empathy, and childish behavior; and ventro- and dorsolateral frontal areas leading to “pseudodementia” or “dysexecutive syndrome” marked by impairments in organization, reasoning, planning, motivation, and self-monitoring (108).


General Treatment Guidelines and Treatment Outcomes

See Table 90-2 for general principles for treating patients with co-occurring PDs and SUDs. The best predictor of therapeutic outcome for PD patients is severity of illness, not type of personality psychopathology (9,111). One would expect that with co-occurring PDs and SUDs, the presence of two distinct disorders, irrespective of etiologic commonality, would raise the issue of bidirectional interaction considering the ways that each disorder might influence the persistence, expression, or progression of the other, thus altering its course, and failure to treat one disorder (either mental illness or the SUD) would be predicted to negatively affect the severity of illness and longitudinal course of the other (112).



From American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association, 2000; Jang KL, Livesley WJ, Vernon PA, et al. Heritability of personality disorder traits: a twin study. Acta Psychiatr Scand 1996;94:438–444; Widiger TA. The DSM-III-R categorical personality disorder diagnoses: a critique and an alternative. Psychol Inq 1993;4:75–90; Ross S. The mentally ill substance abuser. In: Galanter M, Kleber M, eds. Textbook of substance abuse treatment, 4th ed. Washington, DC: The American Psychiatric Publishing, 2008:537–554, Ref. (103).

However, when examining co-occurring PDs and SUDs, the data are mixed as to whether co-occurring PDs in general, in individuals with SUDs, predict a worse response to treatment. A growing number of studies have consistently demonstrated that personality psychopathology, although associated with pre- and posttreatment problem severity, is not a strong predictor of clinical improvement in this population (113119). Alternatively, a number of studies have shown that PDs can predict a shorter time to relapse, worse substance abuse outcomes in general, increased treatment dropout rates, or lack of aftercare compliance after discharge in patients with SUDs (120123). Studies focusing on “normal” personality traits in individuals with SUDs have delineated low persistence, high novelty seeking, high neuroticism, and low conscientiousness as strong predictors of a shorter time to relapse (49).

Other factors that have been identified as positively affecting treatment outcomes in individuals with co- occurring PDs and SUDs include higher level of motivation for change, longer length of time in treatment, and increased therapist alliance (117,121,124). Regarding the comorbidity of Axis I and Axis II disorders, it has been demonstrated that PDs are associated with worse outcomes for patients with a broad range of Axis I diagnoses including SUDs (125). Prospective longitudinal outcome studies of SUD patients with both Axis I and Axis II disorders suggest that having a combination of both Axis I and Axis II disorders, more so than either disorder alone, predicted worse outcomes such as increased likelihood of relapse (126) or worse psychosocial outcomes (127,128). Co-occurring non-SUD Axis I psychiatric pathology in individuals with PDs and SUDs (“triply” diagnosed) has also been associated with worse treatment outcomes in terms of aftercare compliance (123).

Psychosocial Treatments

Despite a relative abundance of research into the efficacy of different types of psychotherapies for those with singly diagnosed PDs or with SUDs, only a small number of studies have evaluated the efficacy of integrated psychotherapy approaches to treat those with co-occurring PDs and SUDs (129). Therefore, the literature on the efficacy of psychotherapies for singly diagnosed PDs or SUDs is a good place to start to develop a psychosocial treatment strategy.

Substance Use Disorders

The psychosocial treatments that have demonstrated efficacy for SUDs in randomized controlled trials (RCTs) and meta-analyses include brief interventions, motivational interviewing, cognitive–behavioral therapy (CBT) interventions such as relapse prevention, contingency management (CM), community reinforcement, couples therapy, family therapy, contract therapy, social skills training, case management, and 12-step interventions (Alcoholics Anonymous [AA], Narcotics Anonymous [NA], 12-step facilitation) (130133).

Cluster A Disorders

Even though some PD experts recommend psychotherapy as the optimal treatment for individuals with cluster A disorders (134), there are no published RCTs in the literature evaluating psychotherapeutic interventions for any of the cluster A disorders; however, several case reports or uncontrolled studies have suggested the efficacy of certain psychotherapeutic techniques, specifically psychodynamic psychotherapy, CBT, supportive psychotherapy, or mixed approaches (135). A more structured setting (i.e., inpatient, day program) with a greater dosed intensity of psychosocial treatment may be better than nonintensive outpatient treatment. In a prospective nonexperimental, nonrandomized study of individuals with cluster A PDs, comparing inpatient treatment (average treatment duration 9 months) to day treatment (average treatment duration 10 months) to outpatient treatment (average treatment duration 13 months), those in the inpatient and day treatment groups demonstrated significantly greater improvements in global functioning, greater core PD symptom reductions, and improved quality of life (109).

Cluster B Disorders

The cluster B disorders have by far received the most attention in the psychotherapy literature compared to either the cluster A or the cluster C disorders, with the majority of psychotherapy RCTs being conducted for these disorders (136).

Borderline PD

Several psychotherapeutic interventions for BPD have been specifically developed and evaluated in RCTs: dialectical behavioral therapy (DBT) (137), transference-focused psychotherapy (TFP) (138), schema-focused therapy (SFT) (139,140), and mentalization-based therapy (MBT) (141). DBT was the first psychotherapy specifically designed to treat BPD and has received the most empirical attention in research settings. DBT is a type of CBT integrated with Eastern mindfulness techniques that specifically addresses skill deficits, maladaptive cognitions, and self-injurious behavior in patients with BPD (137). The modified version adapted for patients with SUD is DBT substance abuse (DBT-S), which includes the standard components of DBT plus a focus on abstinence issues, improving motivation for change, additional modified skills, and strategies to strengthen the therapeutic alliance by enhancing the therapist’s skills and motivation to engage difficult, “easily lost” patients (142). Several RCTs in both inpatient and outpatient settings have demonstrated the efficacy of DBT compared to a control group (usually treatment as usual [TAU]), and a meta-analysis of DBT (including eight RCTs and eight non-RCTs) demonstrated moderate treatment effect sizes for reducing parasuicidal and suicidal behaviors (143). TFP is a psychodynamic-based intervention that theorizes that splitting (intrapsychic and interpersonal) is a core source of pathology in BPD leading to identify diffusion, interpersonal dysfunction, and affect dysregulation (144). The treatment focuses on the analysis and utilization of the relationship between the patient and therapist to allow the patient to more accurately perceive and optimally respond to interpersonal relationships (135). TFP has been evaluated in several RCTs. In one of the RCTs with approximately 100 participants randomized to outpatient TFP versus treatment by experienced community clinicians, compared to the community treatment group, the TFP group demonstrated statistically significant enhanced improvements in core BPD symptoms, improved psychosocial functioning, fewer suicide attempts, less inpatient admissions, and approximately a 50% lower dropout rate (145). In another RCT of 90 participants randomized to yearlong outpatient treatment of TFP versus DBT versus supportive dynamic psychotherapy, all three modalities demonstrated significant reductions in depression and anxiety as well as improvements in global functioning, DBT and TFP were significantly associated with reductions in suicidal behavior, and only TFP was significantly predictive of reductions in irritability, impulsivity, and aggressive behavior toward others (138). SFT is a cognitive–behavioral intervention based on identifying maladaptive cognitive schemas that develop as a result of adverse childhood events and lead to cognitive distortions associated with BPD (139). Two RCTs have demonstrated the efficacy of SFT for BPD in outpatient settings (139,146). In an outpatient comparative effectiveness RCT of 88 participants randomized to SFT versus TFP, at 3-year followup, both groups demonstrated significant improvements in all core BPD symptoms and improved quality of life, while the SFT group was superior to the TFP group in terms of the degree of clinical improvement or recovery from BPD as well as improved general psychopathologic dysfunction (139). MBT is a type of psychoanalytic and social cognitive intervention based on attachment theory and theorizes that impairments in mentalization (defined as a mental activity that allows one to perceive and interpret behavior in terms of intentional mental states) lead to core pathologies associated with BPD, specifically difficulties in differentiating mental states of self and others; MBT is delivered in individual and group formats and focuses on improving the patient’s ability to mentalize in the context of attachment relationships (141). Several RCTs of MBT versus TAU, delivered in a day treatment or outpatient setting, have demonstrated superiority of the MBT group versus TAU in terms of improvements in core BPD symptoms, fewer suicide attempts, and improved psychosocial functioning (147150).

Antisocial PD

Once considered to be an untreatable disorder, there is growing promise for utilizing psychosocial interventions to treat ASPD as demonstrated by research over the last two decades (135). Regarding the efficacy of family-based interventions for juveniles with conduct disorder, several controlled trials have demonstrated the efficacy of multisystemic family therapy versus controls in terms of lower rates of recidivism, reductions in deviant peer affiliation, and improved familial communication (151153). In a meta-analysis of 42 studies of psychotherapy for the psychopathic variant of ASPD, there was evidence for the benefits of psychotherapy (psychodynamic psychotherapy, CBT, or mixed approaches) versus control conditions in terms of reductions in psychopathic behaviors (i.e., decrease in lying, increase in empathy or remorse, improved interpersonal functioning) with the most successful interventions being intensive (i.e., average of four sessions per week for 1 year) and consisting of a combination of individual, group, and family therapies (110). In one psychotherapy RCT that evaluated ASPD, of 52 adult men with ASPD with acts of aggression in 6 months prior to study entry who were randomized to 6 months of CBT plus TAU versus TAU alone, there was a trend toward improvement of the CBT-augmented group with respect to problematic drinking, social functioning, and beliefs about others (154).

Two RCTs have examined the efficacy of psychosocial interventions for individuals with co-occurring ASPD and SUDs. The first RCT examined individuals with opioid dependence on methadone maintenance (MM), an intervention that has consistently been associated with a variety of positive outcomes such as decreased illicit drug use, decreased mortality, reduced rates of HIV, increased engagement in prosocial activities, and reduced criminal behavior (155). In one of the RCTs, of 40 opioid-dependent patients on MM randomized to an intensive behavioral approach, CM, versus MM TAU without CM, short-term outcomes (i.e., 4-month follow-up) demonstrated improvements in both groups in terms of substance abuse outcomes (i.e., use reduction, abstinence) and psychosocial outcomes (156). This suggests that MM treatment can be an effective treatment for individuals with co-occurring ASPD and an SUD irrespective of whether a more intensive behavioral component is part of the treatment. However, given the small sample size of this study and given the substantial evidence base supporting the efficacy of CM (157160) in individuals with SUDs, further investigation is needed to ascertain if adding a more intensive psychosocial intervention like CM can improve outcomes in those with co-occurring ASPD and SUDs. A well-designed study that provided such support was an RCT of 108 opioid-dependent participants on MM with comorbid cocaine dependence, with and without co-occurring ASPD who were randomized to four study conditions: CM alone, CBT alone, CBT + CM, and MM alone (control). At follow-up, those with ASPD in all three treatment conditions were more likely to be abstinent from cocaine use than those without ASPD, and the treatment effect for the ASPD was largely due to the CM intervention as this treatment condition had significantly improved abstinence rates compared to the CBT only and CBT + CM groups (161).

Narcissistic and Histrionic PD

There are no RCTs in the literature evaluating the efficacy of psychotherapies for narcissistic personality disorder (NPD) and HPD, and the available evidence suggests that these are difficult to treat disorders associated with poor outcomes and high dropout rates (136,162164).

Cluster C Disorders

Of the cluster C PDs, psychotherapies for avoidant PD have been the most studied. Several RCTs have demonstrated core reductions in APD symptoms (i.e., decreased anxiety, increased social functioning) with several different psychotherapies demonstrating efficacy including social skills training with gradual exposure to social situations, psychodynamic psychotherapy, and CBT (165167).

There are no published RCTs examining the efficacy of psychosocial interventions for either OCPD or dependent PD (135).

Integrated PD and SUD Psychosocial Treatments

There have been two RCTs for DBT-S conducted in outpatients with comorbid SUD and BPD. The first study compared DBT-S to a community-based TAU, and the second study compared DBT-S to comprehensive validation therapy plus a 12-step approach (CVT + 12S). In the first RCT, compared to the TAU group, the DBT-S group had significantly greater reductions in substance abuse throughout the treatment period and including up until the final follow-up point at 16 months and had significantly superior improvements in global and social functioning at follow-up (168). In the second RCT, the DBT group maintained reductions in opioid use throughout the 12 months of treatment, while the CVT + 12S group significantly increased opioid use during the final 4 months of active treatment; both groups demonstrated significant reductions in psychopathology from baseline to the 16-month follow-up point (169). Given the substantial evidence base in support of DBT for BPD and the data from the two above-mentioned RCTs of DBT-S in those with BPD and co-occurring SUDs, it would seem reasonable to include DBT or DBT-S as a standard treatment modality for those with co-occurring BPD and SUDs in either substance abuse or mental health treatment settings. However, it may not be readily available especially since most substance abuse programs do not have expertise in delivering DBT and often DBT programs, inexplicably, exclude people with SUDs.

Dual-focus schema therapy (DFST) is a manualized CBT delivered in an individual psychotherapy format and represents the first attempt to develop an integrated approach across the spectrum of PDs that co-occur with SUDs (170). It focuses on identifying maladaptive cognitive schemas associated with various PDs and acquiring new coping skills for symptom-focused relapse prevention. Three RCTs have evaluated the efficacy of DFST. In one of the RCTs comparing DFST to 12-step facilitation (TSF) in outpatients on MM, DFST demonstrated improved substance abuse outcomes and stronger therapeutic alliance between therapists and participants compared to TSF (171). In an RCT comparing DFST to standard group substance abuse counseling (SAC) in a cohort of homeless men with PDs and SUDs, although the DFST group overall demonstrated greater therapy utilization than the SAC group, individuals with more severe PD symptoms had better utilization of SAC compared to DFST (172). In another RCT comparing DFST with individual drug counseling in a residential treatment setting of individuals with co-occurring PDs and SUDs, contrary to the author’s hypothesis, although both interventions led to overall reductions in PD symptoms at 6-month follow-up, individual drug counseling resulted in more sustained PD symptom reductions compared to DFST (173).

Therapeutic communities (TCs) were developed in the 1960s to specifically treat individuals with severe addictive spectrum disorders with comorbid antisocial traits. The core principles underlying TCs include provision of a highly structured daily routine; “community as method” approach where the peerled community provides the active treatment ingredient through a combination of positive reinforcement, negative reinforcement, and coercion; promoting personal responsibility and self-reliance by developing vocational and independent living skills; and promoting prosocial values within a hierarchical social network that sustains abstinence and recovery (174,175). Community-based residential TCs have demonstrated efficacy in reducing substance use, reducing criminality, and increasing employment in prospective, longitudinal trials (176178). RCTs have demonstrated the efficacy of prison-based TCs in reducing substance abuse and recidivism relative to the control condition (179,180), and a meta-analysis of 15 trials evaluating TCs in correctional settings concluded that TCs were associated with significant positive reductions in recidivism (181). TCs have further been modified to treat individuals with co-occurring disorders in the criminal justice system, and two RCTs have demonstrated improvements in the modified TC group compared to TAU in terms of reductions in recidivism and reincarceration rates (175,182). Even though it would appear that TCs would be a specific type of integrated treatment program for individuals with co-occurring ASPD and SUDs, research specifically evaluating retention among individuals with co-occurring ASPD and SUDs in TCs has been mixed. For instance, at least one study has found ASPD to be positively associated with treatment retention (183), others have found ASPD to be negatively associated with treatment retention (184), while other studies have found that ASPD is not related to treatment retention outcomes (185187). Several studies have demonstrated that the presence of any PD is associated with worse retention in a TC compared to the absence of any PD (187189).

Similar to TCs, AA, NA, and other 12-step mutual-help groups can be conceptualized as integrated psychosocial interventions for those with co-occurring PDs and SUDs. Twelve-step philosophy incorporates a broad array of therapeutic modalities that can operate on multiple change levels: spiritual/religious changes (i.e., spiritual awakening), cognitive, affective, behavioral, and social. Several of the 12-steps and the program more broadly address personality psychopathology. The participant surrenders himself or herself to a higher power, makes a personal inventory of transgressions with a focus on how one has harmed others, reveals this to a sponsor and one’s higher power, makes “amends” to those he or she has wronged, and then provides ongoing community service and has a duty to pass on the message he or she has received. A set of moral codes and behaviors is prescribed along with abstinence within a social and communal network. These are antinarcissistic and prosocial steps that deinvest from the self and reinvest into the group or community (190). AA is more than a methodology to maintain abstinence from alcohol and can be considered more broadly in social terms. More than helping addicts stay abstinent, it provides a means for recovery by acting as a steady and readily available community of connection, cohesion, and meaning. Furthermore, it promotes a sense of community over the self through its antin-arcissistic steps (i.e., taking personal inventory and making amends, asking for forgiveness) and through its altruistic commitment to helping others and spreading the message of AA (i.e., 12th step) (191,192). In support of this, there is some evidence that being a sponsor in AA and mentoring/supporting others in their recovery is associated with positive outcomes (193,194). Over the past 15 years, cross-sectional, retrospective, and increasingly rigorous longitudinal research (supported by two meta-analyses for AA) (133,195) has established the efficacy of 12-step interventions and supports the association between 12-step participation and positive substance abuse outcomes (both short and longer term), with therapeutic benefits similar to professional interventions, and evidence to support its use as a cost-effective adjunct and complement to standard treatment (196204). There are no published RCTs examining 12-step interventions specifically for PDs and co-occurring SUDs. This is an area of inquiry that deserves further investigation.

Pharmacologic Treatments

Pharmacotherapy can serve as a useful adjunct to psychotherapy in the treatment of dually diagnosed PD patients by targeting specific symptom domains of PDs and possibly by reducing substance abuse. Like psychosocial interventions, there is a paucity of research examining pharmacologic interventions for individuals with co-occurring PDs and SUDs leaving only the literature on the pharmacotherapy for singly diagnosed PDs or SUDs to draw from. Pharmacotherapies to treat SUDs are established for nicotine, opioids, and alcohol (with FDA-approved medications) but not available for any other class of drug of abuse (205). These treatments will not be reviewed here as they are extensively reviewed in other sections.

In the early 1990s, the PD field underwent a paradigm shift away from the notion that only Axis I disorders ( considered biologic/neurologic in etiology) warranted treatment with pharmacotherapy, whereas Axis II disorders (alternatively considered psychological in origin) were treated only with psychosocial interventions. This led to an increase in research examining the efficacy of pharmacotherapies to treat specific domains of personality psychopathology. From the perspective of considering the neurobiologic basis of PDs, a pharmacologic approach to treatment is based on a symptom-specific approach utilizing medications to influence neurotransmitter systems and brain regions that might underlie the expression of dimensional personality biologic trait pathology (i.e., affect dysregulation, impulsivity) and acute-statesymptomatology (i.e., depression, anger) (206). Siever and Davis (10) provided one of the first models considering PDs from a neurobiologic perspective and conceptualized Axis II symptoms broadly on a dimensional spectrum with certain Axis I disorders and focused specifically on the following core symptom dimensions common across PDs: affect dysregulation (i.e., angry, depressed, mood instability, rejection sensitivity) continuous with mood disorders (i.e., depression and bipolar disorders), cognitive–perceptual symptoms (i.e., psychoticism–paranoid ideation, referential thinking, illusions, derealization) continuous with psychotic spectrum illnesses, impulsive–behavioral dyscontrol (i.e., impulsive aggression, self-harm, substance abuse) continuous with impulse control disorders, and anxiety/inhibition continuous with anxiety disorders.

Of the common domains mentioned, the first three (affective, cognitive, impulse symptom domains) have garnered the most attention as they tend to produce more problematic and urgent symptoms such as violence and suicidal behaviors (206). BPD has by far been the most studied PD in terms of psychopharmacological research followed by schizotypal PD (SPD) and then ASPD. The other PDs have essentially not been empirically studied from a pharmacologic intervention perspective. Even though there are no FDA-approved pharmacotherapies for PDs and despite their lack of adequate empirical support, patients with PDs are prescribed medications at one of the highest rates for all diagnostic groups (207).

Cluster A: Schizotypal PD

Cognitive–perceptual abnormalities (i.e., psychotic-like symptoms, cognitive deficits) and interpersonal dysfunction are the hallmarks of SPD. Psychotic-like symptoms (alterations in cognition, perception, affect) centrally define SPD, which exists along the schizophrenia spectrum (208).

Antipsychotics have been more extensively studied than any other class of medication for PDs with the majority of studies done in patients with BPD and SPD (206). For schizotypal PD, meta-analyses of RCTs of typical and atypical neuroleptics have demonstrated efficacy in reducing both cognitive–perceptual psychotic-like symptoms (moderate effect size) and anger/hostility (moderate to large effect size) within the affect dysregulation dimension (209). Despite improving psychoticism and angry affect, low-dose antipsychotics do not lead to remission of schizotypal disorder, do not improve social cognitive dysfunction (i.e., social isolation, deficits in relatedness), and are associated with well-known side effect–induced toxic syndromes (i.e., tardive dyskinesia for typicals and metabolic syndrome for small for gestational ages). As such, they should be used with caution and only as necessary especially if the symptoms are largely ego-syntonic for the individual and they don’t want to medicate away parts of themselves they may like and, for example, consider creative. Besides SPD, there is little evidence to suggest the utility of using antipsychotics in schizoid or paranoid PDs (210). Cognitive enhancement by dopaminergic or noradrenergic alpha-2A agonist is a possible future avenue of research (207).

Cluster B: BPD

BPD consists of several symptom domains of dysfunction: affective instability, intense and unstable relationships, identity diffusion, transient psychotic-like symptoms, impulsivity, anger, and self-injurious behaviors (211). Although there are no FDA-approved medications to treat BPD and despite their lack of global clinical improvement associated pharmacotherapies, their use in clinical practice is common where patients receive an average of three medications with a significant increase in prescriptions written for antipsychotics and mood stabilizers over the last decade (212).


Regarding the efficacy of antidepressants in BPD, several meta-analyses have been performed and demonstrate that ADs have small but significant effects on reducing anxiety, anger, aggression, and impulsive self-harm although they have limited to no efficacy in reducing depression and chronic emptiness and have no effect on global functioning or remission of BPD (209,213). The efficacy of serotonin-specific reuptake inhibitors (SSRIs) is limited with more consistent effects on anger, aggression, and self-harm as compared to mood lability and depression (213217). Tricyclic antidepressants and monoamine oxidase inhibitors should be used with caution especially in patients with suicidality, noncompliance, comorbid medical illness (i.e., cardiac), and potentially hazardous drug–drug interactions.


Evidence from several meta-analyses including RCTs and open-label studies suggests that antipsychotics are effective at treating affect dysregulation (anger) and impulsive–behavioral dyscontrol core symptoms of BPD as well as reducing cognitive–perceptual symptoms (i.e., micro-psychotic) (209,218221). However, there were no significant differences in overall dropout rates between patients on medications and those on placebo (217), and total BPD severity was not significantly affected (219).

Mood Stabilizers

Despite BPD being considered by some on the bipolar spectrum (222), there is little evidence to definitively support this link, and although mood stabilizers commonly effect treatment remission in bipolar disorder, they do not lead to remission of BPD (223). In a meta-analyses of 21 placebo-controlled RCTs from 1980 to 2007 examining the effect sizes of pharmacologic interventions for borderline PDs, mood stabilizers had a very large effect on impulsive– behavioral dyscontrol and anger, a large effect on anxiety, a moderate effect on depressed mood, and a more pronounced effect on global functioning than antipsychotics (209). The only RCT of lithium in BPD showed reductions in affective instability but no changes in global clinical improvement (224). Anticonvulsants have been shown to be effective in treating certain symptom clusters of BPD. Carbamazepine has been shown to reduce behavioral dyscontrol (i.e., impulsivity), anxiety, anger, and suicidal behavior (225,226). Like the SSRIs, valproic acid is more effective at treating anger and impulsive aggression rather than affective instability (220). A smaller dataset exists for topiramate (227) and lamotrigine (228) with studies showing decreased anger and anxiety and less mood instability. In summary, mood stabilizes may be useful for impulsive–behavioral dyscontrol (i.e., aggression) and affective symptoms, but less so for affective instability in patients with BPD (220).

Cluster B: ASPD

Meta-analysis of controlled trials to treat ASPD has only been conducted with nortriptyline, bromocriptine, and phenytoin, and although there is some evidence for a reduction in impulsive aggression, this is not a consistent finding, and currently, pharmacotherapy is not a standard part of treatment for ASPD (229).


PDs commonly occur in both psychiatric and substance abuse treatment settings, and there is considerable co-occurrence between PDs and SUDs, especially with ASPD and BPD. Screening, the use of standardized diagnostic assessments, FH, age of onset of symptoms, premorbid symptom patterns, temporal history of PD symptoms versus substance initiation and ongoing use, periods of abstinence, collateral history, the use of serial and longitudinal assessments, and ruling out substances of abuse or medical conditions that can masquerade as PD symptoms are key to establishing the diagnosis of an independent PD. Patients with co-occurring SUDs and PDs can benefit from treatment as much as those without PDs, but the presence of a PD does negatively affect the course of treatment of the addictive disorder and is associated with noncompliance and relapse. It is therefore important to continue treatments specifically aimed at the PD so as to minimize the impact of specific PD symptoms on poor substance abuse outcomes. It is important to provide comprehensive care, optimally within a structured environment (i.e., Dual Diagnosis Day Program, Methadone Maintenance Treatment Program [MMTP], TC) with a dual focus (i.e., PD and SUD), in an integrated system of care, and utilizing symptom-targeted pharmacotherapy when appropriate as an adjunct to psychosocial interventions. A focus on therapeutic alliance, risk assessment, as well as addressing motivational/interpersonal/perceptual problems are key to engage patients in longer-term treatments that are associated with improved outcomes. Utilize integrated psychosocial treatments developed specifically for PDs and SUDs (i.e., DBT-S) when possible, although additional training is necessary for this and the logistics and resources for such large-scale training need to be considered.


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