13 - Pharmacologic Treatment of Personality Disorders - A Dimensional Approach

Editors: Shader, Richard I.

Title: Manual of Psychiatric Therapeutics, 3rd Edition

Copyright 2003 Lippincott Williams & Wilkins

> Table of Contents > 13 - Pharmacologic Treatment of Personality Disorders: A Dimensional Approach

13

Pharmacologic Treatment of Personality Disorders: A Dimensional Approach

James M. Ellison

Richard I. Shader

Personality disorders affect between 5% and 10% of the general adult population in the United States. Most such persons are unaware of their disorder, and thus they seek no treatment; nonetheless, they sustain a chronic impairment of social and occupational functioning, an increased propensity to substance abuse, and frequent legal complications. Patients with personality disorders often present treatment requests that are not well addressed by the established uses of pharmacotherapy. Some of the most challenging dilemmas encountered in clinical practice are balancing patients' goals with the potential risks and benefits of available pharmacotherapeutic agents. In the absence of any comprehensive and definitive explanatory model, portions of this chapter focus on a review of selected issues and hypotheses concerning personality disorders.

Many efforts have been made to capture the essence of personality and its disorders; in this process, the theoretic pendulum has swung to and fro between the domains of biology and psychology. The psychodynamic approach to personality disorders that was widely accepted during the preceding century attributes the origins of personality disorders to conflicts, ego deficits, or impaired object relations. From the time of Hippocrates, another view of personality disorders has suggested that they originate from biologic factors, either inherited or acquired, within the central nervous system.

The Hippocratic concept of temperaments (i.e., inherited physiologic predispositions to observable behavioral traits or patterns) resembles the more modern concept of personality dimensions. In the 1940s, Eysenck used factor-analytic mathematic techniques to demonstrate the validity of a model that accounted for much of the variance of personality on the basis of three dimensions: introversion-extraversion; neuroticism, an index of emotional instability; and psychoticism, a measure of antisocial tendencies. Other researchers have considered these dimensions useful and valid.

A somewhat different approach focuses on clinical observation and description to explain and codify personality and its disorders. One such system of classification pioneered by Schneider subsequently evolved into the system still present in the International Statistical Classification of Diseases and Related Health Problems, tenth revision. This system categorizes personality types and disorders descriptively on the basis of recurrent behaviors or traits. Grounded more solidly in clinical assessment methods than in the techniques of experimental psychology, it differs from dimensional approaches by building a syndromal description from a list of many behaviors, some of which may lack independence or perhaps even validity. Although the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, (DSM-IV) classification uses some different categories, it does resemble the International Statistical Classification of Diseases and Related Health Problems, tenth revision, approach in that it is based on objective description rather than on etiologic inference.

In the multiaxial perspective of DSM, 3rd edition, revised (III-R), personality disorders were placed on an independent axis to differentiate what were considered more stable and persistent disorders from the axis I disorders, which were believed to be more florid and often more episodic. Another prominent goal of placing personality disorders on axis II was to ensure they would not be overlooked. However, this approach seems to ignore certain lines of evidence (e.g., genetic data associating schizophrenia with schizotypal personality disorder) that suggest that some axis II disorders may be milder forms of axis I disorders, not wholly distinct syndromes. DSM-IV tries to mitigate these issues by acknowledging this inherent weakness. As with DSM-III-R, DSM-IV delineates personality disorders according to the predominance of pervasive observable behavioral patterns (e.g., dramatic, odd, impulsive).

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The categoric descriptive approach has stimulated clinical awareness and has contributed to a greater understanding of personality disorders. It has also fostered questioning about the nature of personality and the appropriateness of an etiology-free classification system. Embedded in the DSM-IV approach are a variety of unproved assumptions about the nature of personality that have implications for treatment and research. The very conceptualization of a specific personality configuration as a disorder implicitly assumes that these behavioral syndromes are illnesses rather than informed or voluntary lifestyle choices. The descriptive approach assumes also that these conditions can be identified on the basis of overt behaviors rather than be inferred through dynamic exploration and formulation. Furthermore, the assumption is that these disorders are sufficiently discrete so as to be distinguishable and stable enough that one does not transmute into another. Viewing them as enduring or chronic rather than episodic implies that personality disorders remain present even when they are clinically dormant during less symptomatic or asymptomatic intervals. As has been noted above, their placement on axis II and their separation from axis I disorders imply a discontinuity between the latter disorders (i.e., the more obvious and frequently episodic syndromes) and the chronic maladaptive behavior patterns of personality disorders. To some extent, this separation mirrors treatment approaches that have emphasized somatic therapies for axis I disorders while discouraging them for personality disorders.

In addition to these theoretic concerns, multiple practical difficulties accompany the use of a descriptive categoric model. Personality disorders, as research now clearly shows, often co-occur (i.e., they are comorbid), complicating both diagnosis and treatment. They are also found in the presence of axis I disorders, including depression and substance abuse, with unexpectedly high frequency. As was noted, the relationships between some of the axis I and axis II disorders (e.g., the aggregation within families of patients with schizotypal or paranoid personality disorders and schizophrenia) appear to be integral to the nature of a number of disorders, and this suggests continuity along a pathologic spectrum. When studying treatment interventions, a pure culture or homogeneous cohort of any personality disorder type is usually difficult to obtain. In the typical clinical settings, patients rarely fit neatly into the descriptive categories. Moreover, from a practical standpoint, these categories have been of limited value in pointing toward diagnosis-specific therapeutic approaches. When planning psychotherapeutic interventions, for example, diagnosis is viewed by some as having less value than the clinician's psychodynamic formulation.

Research into the pharmacotherapy of personality disorders has been facilitated by their acceptance and definition as diagnostic entities and by the subsequent availability of research interview protocols and symptom rating scales. Any advance in this knowledge base, however, may also have been impeded by the tendency of some of these disorders' definitions to follow psychologic and theoretic divisions, rather than biologically meaningful ones. Successful pharmacotherapy frequently focuses more on target symptoms than on syndromal diagnoses, treating similar symptoms with the same agent in varying diagnostic contexts. Aggressive or impulsive behavior may respond, for example, to risperidone or carbamazepine in a broad range of patients (e.g., personality disorders, mental retardation, brain damage, posttraumatic stress disorder, schizophrenia). Historically, much of the pharmacotherapeutic research on personality disorders has been carried out in patients diagnosed as borderline personality disorder (BPD) or schizotypal personality disorder (see Tables 13.1 and 13.2). This research approach may be less illuminating than a symptom-based approach to ameliorating target symptoms that are not unique to any specific personality disorder (e.g., impulsivity, lability of affect).

I. Normal Personality and Its Relationship to Personality Disorders

In general, personality refers to a stable configuration of patterns and modes of relating to oneself and others (i.e., behaviors central to one's life adaptation). From the many behaviors that typify any individual, clusters of related traits can be grouped together and can be used to define that individual's position along a behavioral dimension. Experimental psychologists have used factor analysis to develop models that explain much of the variance of personality on

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the basis of a small number of fundamental dimensions. Implicit in this approach is the belief that a dimensional model of personality disorders can be expanded to illustrate a theoretic continuum that extends into axis I and axis II disorders.

TABLE 13.1. DIAGNOSTIC FEATURES OF BORDERLINE PERSONALITY DISORDER (BPD)

BPD is characterized by a pervasive and enduring pattern of unstable and impaired interpersonal relationships, self-image, affects, and impulse control that usually begins during adolescence or by early adulthood. Patients with BPD typically present with at least five of the following features:
  1. Frantic and chaotic efforts to avoid real or imagined abandonment. (Note: It does not include the suicidal, self-mutilating, or other self-injurious behaviors in item 5.)
  2. Unstable and intense interpersonal relationships characterized by alternations between the extremes of idealization and devaluation of these relationships.
  3. Persistent and markedly disturbed, distorted, or unstable self-image or sense of self (e.g., feeling as if one does not exist or as if one embodies evil).
  4. Potentially self-damaging impulsivity manifested in at least two activity areas (e.g., spending money, sexual activity, substance abuse, shoplifting, reckless driving, binge-eating). (Note: This does not include the suicidal, self-mutilating, or other self-injurious behaviors in item 5.)
  5. Recurrent suicidal threats, gestures, or behavior or self-mutilating or other self-injurious behaviors.
  6. Marked affective instability or reactivity of mood (e.g., intense, episodic dysphoria, irritability, or anxiety usually lasting a few hours and only rarely more than a few days).
  7. Chronic feelings of emptiness that the patient frequently localizes to the abdomen or chest.
  8. Inappropriate or intense anger or lack of control of anger (e.g., frequent displays of temper, constant anger, recurrent physical fights).
  9. Severe dissociative symptoms or paranoid thoughts that are transient and typically stress related. (Note: Feeling abandoned is a common stress.)
From the American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Text revision. Washington, D.C.: American Psychiatric Association, 2000, with permission.

Much has been learned about the biology of normal personality from longitudinal, observational, and family studies. One group, for example, identified nine dimensions of temperament and periodically assessed a selected cohort of toddlers until they reached early adulthood. Behavior at age 3 (i.e., behaviors so early in development as to suggest possible constitutional factors) was a stronger predictor of adult behavior than were parental child-rearing attitudes. An interaction between temperament and environmental factors was hypothesized to explain the contribution of each to a developing personality.

Other preliminary work to try to understand the biologic determinants of personality has been conducted by focusing on traits that could be assessed longitudinally. Studies of shyness, for example, have noted persistence of this trait from the toddler stage to later in childhood. In these studies, shy behavior was also correlated with a psychophysiologic profile of autonomic nervous system arousal in response to a novel situation.

Among genetic studies, investigations of personality traits measured in monozygotic and dizygotic twins separated at birth suggest that as much as 50% of the variance in these traits may be attributed to genotype. This indicates that a substantial component of personality is heritable.

An attractive explanation for the dimensionality of personality and the continuity of normal personalities with axis I and axis II disorders is the hypothesis that biologic factors produce a temperament that interacts with environmental factors. This interaction molds behavioral traits and coping styles. Personality,

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then, is the result of environmental shaping of temperamental possibilities. A greater or lesser expression of inherited tendencies through the overlay of environmentally shaped behavior could then account for a spectrum of personality configurations ranging from normative to pathologic.

TABLE 13.2. DIAGNOSTIC FEATURES OF SCHIZOTYPAL PERSONALITY DISORDER

Schizotypal personality disorder (SPD) is characterized by a pervasive and enduring pattern of social deficits and impaired interpersonal relationships that is manifested as acute discomfort with and reduced capacity for closeness and of cognitive or perceptual distortions and eccentricities of behavior; it usually begins in adolescence or by early adulthood. Patients with SPD typically present with at least five of the following features (note: these must not be present only during discrete periods in which mood is clinically altered [e.g., depression, anxiety, anger])a:
  1. Ideas of reference, excluding delusions of reference;
  2. Odd or unusual beliefs that are not consistent with cultural or subcultural norms or magical thinking that influences behavior (e.g., superstitiousness, belief in clairvoyance, telepathy, or a sixth sense, belief that others can feel my feelings ; in children and adolescents, bizarre fantasies or preoccupations may be present);
  3. Unusual perceptual experiences, including somatosensory (bodily) illusions or distortions;
  4. Odd or unusual thinking or speech that is not associated with loosening of associations or incoherence (e.g., vague, circumstantial, metaphoric, overelaborated, or stereotyped);
  5. Suspiciousness or paranoid thoughts;
  6. Inappropriate or constricted affect (e.g., appears distant, cold, aloof);
  7. Behavior or appearance that is odd, eccentric, or peculiar;
  8. An absence of close friends or confidants (or only one) other than first-degree relatives that results primarily from a lack of desire, pervasive discomfort with others, or eccentricities;
  9. Excessive social anxiety (e.g., extreme discomfort in social situations that does not diminish with familiarity and that tends to be associated with paranoid fears rather than with negative judgments about self).
aThese features must not occur exclusively during the course of schizophrenia or another psychotic disorder, a mood disorder with psychotic features, or a pervasive developmental disorder.
From the American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Text revision. Washington, D.C.: American Psychiatric Association, 2000, with permission.

II. Dysfunctional Personality Traits and Personality Disorders

The nature of maladaptive or dysfunctional personalities is still incompletely understood. Family studies of antisocial, paranoid, and schizotypal personality disorders suggest strong components of heritability. Some efforts have been made to trace traits such as impulsivity and affective instability among the relatives of patients with BPD. Still, many important aspects of these disorders (e.g., sensation-seeking, suspiciousness, cognitive slippage) require further study.

Although most work on the treatment of personality disorders has made categoric distinctions, some authors have sought to identify and to target for treatment the hypothetic dimensions of psychopathology that span multiple DSM-III-R axis II categories. These dimensions, unlike those used to define normal personality, have arisen from clinical observation rather than from factor analysis. The resulting dimensions appear to be heterogeneous and they may lack independence, yet they serve as a useful beginning in the development of a functional and potentially unifying perspective.

A. Cognitive and Perceptual Style and Organization

These may be defined as a person's capacity to receive, process, and respond selectively to important external stimuli and to use these inputs, along with previous experiences, to plan and implement subsequent actions. Impairment in this function could reveal itself, for example, as suspiciousness, paranoia, or distortion of others' intentions (see Chapter 4). Such dysfunction

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might lead to social isolation and further decrements in reality testing. Impairment along this dimension is particularly characteristic of schizotypal and paranoid personality disorders, but it may be seen in patients with other personality disorders (e.g., the all or nothing thinking of patients with BPD). Evidence suggesting a biologic basis of some alterations in this dimension in patients with schizotypal personality disorder continues to accumulate.

Abnormalities of smooth pursuit eye movements and impaired performance on tests of visual and auditory attention, similar to that which may be found in some patients with schizophrenia, have been associated with social withdrawal and other deficit symptoms in schizotypal patients. Psychotic exacerbations among some such patients have been associated with elevated levels of plasma and cerebrospinal fluid homovanillic acid, a finding consistent with the hypothesis of an underlying abnormality of dopaminergic activity.

B. Impulsivity and Aggression

These traits may be viewed as the consequences of a lowered threshold to respond with action in the face of external or internal stimuli. Some action-oriented persons seem to be stimulus seekers; their craving for and, at times, impulsive pursuit of excitement appear to be directed at achieving an altered internal state. Action-oriented stimulus-hungry persons seem to have a high need for novelty. Impulsive persons often have difficulty delaying action, they tend to externalize the sources of their difficulties, they express aggression or frustration easily, and they may be less likely to experience guilt or anxiety. Excessive impulsivity is frequently found in overdramatizing patients and is manifested variably as self-injurious behavior, suicidality, aggressive behavior directed at others, or substance abuse. Some studies suggest that antisocial personality disorder, which prominently features impulsivity and aggression, has a heritable component. Impulsivity has been found to be unusually frequent among the relatives of patients with BPD.

Impulsive or aggressive behaviors may represent a common pathway of expression for several different dysfunctional states. Among possible etiologies, the following appear to be of particular importance in treatment planning.

  • Cerebral cortical dysfunction. Some impulsive persons may suffer from cerebral cortical dysfunction. Early studies using electroencephalographic techniques and provocative testing with procaine injections attempted to correlate impaired control of impulsivity with temporolimbic seizures. Although subsequent investigations have not confirmed this hypothesis, positron emission tomography results have suggested a link between impulsive aggression and orbitofrontal hypometabolism.

  • Serotonergic pathway alterations. A number of studies suggest that a dysfunction of serotonergic neurotransmission underlies aspects of impulsive behavior. Some patients with personality disorder who have committed suicide by violent methods or who have displayed violent or aggressive behavior have been found to have decreased cerebrospinal fluid 5-hydroxyindoleacetic acid levels and a diminished prolactin response to the serotonin releaser fenfluramine (see Chapter 17).

  • Adrenergic pathway alterations. Some impulsive persons who exhibit a high degree of self-stimulating or sensation-seeking behavior may have dysfunctional noradrenergic neurotransmission. Evidence consistent with this hypothesis includes studies in which growth hormone responses to clonidine administration were correlated with the presence of aggressive behavior. The noradrenergic system may not be the primary site of dysfunction, however, because serotonergic, noradrenergic, and dopaminergic systems are interactive.

  • Adult attention deficit hyperactivity disorder (ADHD) (see Chapter 22). Some persons with impulsive or distractible behavior may be demonstrating elements of an adult form of ADHD. In such persons, a

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    childhood history of ADHD is typically present. This presentation may be misdiagnosed as antisocial personality disorder, or it may serve as an antecedent to personality changes consistent with that disorder.

C. Affective Instability

This disorder can be defined as a vulnerability to rapidly shifting mood states that are reversible and reactive to environmental events (e.g., separation, loss, frustration, rejection, criticism). Some affectively unstable persons appear highly reward dependent ; they feel good when they are receiving praise or applause, even in symbolic forms. Their moods may rapidly plummet, however, when they feel neglected, unwanted, or unappreciated. At times, affective instability may form the basis for dysfunctional interpersonal sensitivity. Impairment of affective stability may result in fluctuating self-esteem, inhibited or avoidant behavior, or difficulties in modulating emotional responses. Disturbances of this dimension are particularly common among patients with histrionic, borderline, narcissistic, and antisocial personality disorders. Among the family members of some patients with BPD, the trait of affective instability has been shown to be relatively frequent. Some have hypothesized that this lability represents a variant form of mood disorder, because disordered mood is also frequent among the relatives of patients with BPD. This is consistent with the observation from sleep studies of shortened rapid eye movement latency, a putative marker of major depression, in some patients with BPD.

D. Anxiety

Anxiety (see Chapter 14), which may at times appear as high harm avoidance, is most likely a dimension of personality with heterogeneous origins, involving physiologic and subjective responses to novelty or threat. Patients with avoidant, borderline, compulsive, dependent, or histrionic personality disorders may experience excessive anxiety. As noted earlier, one hypothesis is that heightened autonomic reactivity in the face of novel stimuli characterizes some individuals who are excessively shy. No unifying biologic basis, however, has been convincingly identified for this personality dimension. Panic attacks are frequent among overdramatizing patients with personality disorders; they can also occur in people of all ages who have no obvious underlying psychopathology. The free-floating anxiety seen in many anxious patients most likely has a different basis.

III. A Dimensional Approach to the Use of Pharmacotherapy; Empiric Pharmacotherapy Findings from the Literature

For many years in the United States, individual insight-oriented psychotherapy has remained the mainstay of treatment of personality disorders; this pattern has persisted even though studies confirming its efficacy are limited. Self-psychology, supportive therapy, cognitive-behavioral approaches, dialectic behavior therapy, and group therapy are also advocated and practiced. In recent years, some attempts have been made to elucidate shared or differentiating features of these disorders relevant to psychotherapeutic interventions.

Medications are still regarded by some patients and clinicians as superfluous or harmful to the treatment of personality disorders. Others regard pharmacotherapy as acceptable, but primarily in a symbolic sense as a tangible manifestation of the therapist's effort to relieve the patient's suffering. This view is reflected in the following paraphrased statement of one such authority: Just as you cannot teach a foreign language by giving a medication, you cannot expect medication to change character. Results, however, from a growing body of empiric medication trials undertaken in patients with personality disorders suggest that pharmacotherapy can diminish the intensity or frequency of certain symptom patterns. These studies have been conducted in patient groups selected for their diagnostic homogeneity. Because of the unavoidable and inevitable comorbidity for additional personality disorders in these cohorts, however, considering them also to be studies of the treatment of symptom dimensions across these comorbid disorder categories seems plausible.

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A. For Cognitive and Perceptual Abnormalities

The usefulness of low-dose treatment with antipsychotic agents was initially reported before DSM-III in a small cohort of patients termed borderline, each of whom also had at least one persistent psychotic symptom. None had responded completely to any of a variety of prior medications. With conventional antipsychotic agents, however, improvement was observed across a range of symptoms, including tangentiality, distractibility, social withdrawal, thought slippage, cognitive dysfunction, and overt psychotic symptoms. In an uncontrolled trial in 80 outpatients with BPD, reductions of hostility and suspiciousness were observed after treatment with either loxapine (mean daily dose, 14 mg) or chlorpromazine (mean daily dose, 110 mg). In another uncontrolled study, thiothixene (mean daily dose, 9.4 mg) or haloperidol (mean daily dose, 3 mg) diminished psychoticism, illusions, ideas of reference, paranoid ideation, and derealization in 52 outpatients with BPD or schizotypal personality disorder. A subsequent uncontrolled trial suggested that thioridazine (mean daily dose, 92 mg) reduced paranoid ideation in a small group of outpatients with BPD. Among the atypical antipsychotic agents, clozapine (25 to 100 mg per day) has been reported to be helpful in a group of treatment-resistant BPD inpatients with psychotic symptoms, and olanzapine (2.5 to 10 mg per day) has been reported to be helpful in a group of outpatients with BPD and comorbid dysthymic disorder.

Several controlled studies have addressed the effects of antipsychotic agents on cognitive and perceptual dysfunction among patients with BPD or schizotypal personality disorder. Using thiothixene (mean daily dose, 8.67 mg) in 50 such outpatients, one group observed a significant reduction of illusions and ideas of reference. The composition of this cohort of patients was skewed toward schizotypal by a requirement that each patient must have at least one psychotic symptom. Another group compared haloperidol (mean daily dose, 7.24 mg) with amitriptyline (mean daily dose, 148 mg) and noted the superiority of haloperidol for treating paranoid ideation or psychoticism in 64 patients with BPD or schizotypal personality disorder.

In all of these studies, the clinical improvement has been significant but modest. Furthermore, a 16-week continuation-phase study in a cohort of patients with BPD who had initially improved on haloperidol revealed that the improvement was circumscribed and that the treatment discontinuation was disappointingly frequent.

B. Impulsivity and Aggressiveness

These traits, possibly reflecting a more heterogeneous group of behaviors than cognitive or perceptual impairments, have been treated with some success in various clinical populations with a variety of medications. The pathophysiology of aggressivity almost certainly cuts a swath across current personality disorder distinctions. Antipsychotic agents, psychostimulants, anticonvulsants, lithium, monoamine oxidase inhibitors (MAOIs), and selected proserotonergic agents may all have useful, but limited, roles in the treatment of this dimension.

On rare occasions, impulsivity and aggression are the consequences of emerging psychosis in some patients with personality disorders. More often, impaired integration of environmental cues by an individual with a limited repertoire of behavioral responses may lead to impulsive or aggressive reactions in overly frustrating situations. In some instances, antipsychotic agents reduce these symptoms through their antipsychotic actions. More frequently, however, they appear to modulate aggressive behavior in nonpsychotic patients via a nonspecific and inadequately understood quieting effect. Their use, although it has long been established, is increasingly recognized as less focal with respect to this target dimension. Reductions in anger attacks or other aspects of dyscontrol have been noted after the use of antipsychotic agents in patients with BPD or schizotypal personality disorder. In one study, patients with BPD viewed themselves

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as unchanged in impulsivity or suicidality when treated with trifluoperazine, yet they were assessed to be less suicidal by their physicians. Although antipsychotic agents, both conventional and atypical, are not the first-line agents for impulsivity, at low doses they may still have a treatment role as an alternative or complementary intervention.

The use of proserotonergic medications arises from findings linking altered or deficient serotonergic functioning with aggression in patients with personality disorders. Fenfluramine, a serotonin agonist that is no longer available in the United States, was found to reduce suicidal behavior in a small series of patients with various psychotic diagnoses. Fluoxetine, a serotonin reuptake inhibitor, reduced impulsivity and self-injurious behavior in several studies of patients with BPD. Similarly, sertraline, venlafaxine, and citalopram have reportedly reduced aggressiveness, irritability, or self-injurious behavior in reports on small cohorts of patients.

Some aggressive patients may have a neurodevelopmental or neurologic impairment that hampers their capacity to cope with complex and potentially overwhelming external and internal stimuli. For those who suffer from an adult form of ADHD, treatment with stimulants may stabilize functioning and reduce impulsivity, hyperactivity, or hostility (see Chapter 22). When impulsivity is linked with an electroencephalographic abnormality or a history of seizures, a carefully monitored anticonvulsant trial may be of value. Phenytoin, although it is at present rarely used for this purpose, was previously assessed as a treatment for impulsivity. Carbamazepine (average dose of 820 mg per day) was found to improve behavioral dyscontrol, impulsivity, anger, and suicidality in one group of patients with mixed personality disorders. Divalproex sodium (daily dose range of 1,000 to 2,000 mg), gabapentin (mean daily dose, 900 mg), and lamotrigine (daily dose range, 75 to 300 mg) have each been reported as helpful in small series of patients with BPD. Interestingly, some patients without detectable electroencephalographic abnormalities may also respond to an anticonvulsant, thus suggesting that the mood-stabilizing effects of an anticonvulsant may be more relevant to its beneficial effects in these patients than are its antiseizure effects.

Lithium, another mood-stabilizing agent, was studied in a group of patients with emotionally unstable character disorder, a forerunner to the diagnosis of BPD. Its use reduced both impulsivity and mood lability. Another study that investigated the effects of lithium among a group of prison inmates found a reduction in aggressive behaviors with blood levels averaging about 0.9 mEq per L.

Although tricyclic antidepressants have not been shown to reduce aggression (note: amitriptyline was noted to increase suicidality and hostility in one study of patients with BPD), MAOIs have shown some efficacy in at least two relevant studies. One explored the use of phenelzine in patients considered to be suffering from hysteroid dysphoria and found a reduction in behavioral impulsivity at doses of 15 to 75 mg per day. Another noted lower levels of impulsivity among patients treated with tranylcypromine (mean daily dose, 40 mg).

C. Dysphoria and Affective Instability

Although they are often lumped together, these are distinctly different from each other. Dysphoria, an undifferentiated feeling of emotional discomfort, is a disturbance of mood content, and it may reflect underlying major depressive disorder, atypical depressive states, anxiety, rage, boredom, or emptiness. Dysphoria is found in many patients with personality disorders. Tranylcypromine, phenelzine, or isocarboxazid may be effective in alleviating some patients' dysphoria. Others may respond, possibly with less specificity, to benzodiazepines or antipsychotic agents.

The pharmacotherapy of affective instability, which can be considered a disturbance of mood maintenance, is becoming increasingly understood.

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This dimension of personality has responded to several classes of medications. In several studies, antipsychotic agents have been shown to have mood-stabilizing effects. Some investigators have even claimed that the low-dose use of antipsychotic agents can result in a reduction of excessive rejection sensitivity. As early as the 1960s, chlorpromazine use was noted to have a stabilizing effect on affective functioning, and, in a comparison with amitriptyline, haloperidol has been shown to be more helpful in stabilizing mood. Haloperidol (mean daily dose, 3 mg) and thiothixene (mean daily dose, 9.4 mg) were both observed to improve interpersonal functioning in one uncontrolled comparison. In a placebo-controlled trial, trifluoperazine (mean daily dose, 7.8 mg) improved patient-rated depression and rejection sensitivity. More recently, thioridazine (mean daily dose, 92 mg) and olanzapine (mean daily dose, 7.7 mg) were separately reported in small cohorts to reduce dysfunctional interpersonal sensitivity.

Antidepressants of all categories have also been used to treat dysphoria or affective instability. Tricyclic antidepressant use has yielded mixed results. Both amitriptyline and imipramine have helped in some patients, but they may have worsened mood lability in others. Unfortunately, when increases in anger, hostility, or suicidality occur, determining whether such worsening reflects the underlying disorder or if it has arisen secondary to treatment is not possible. The presence or history of hypomanic symptoms in a patient probably should discourage the use of cyclic antidepressants for treating affective instability. Mianserin, an antidepressant that is not marketed in the United States and that is structurally related to mirtazapine, failed to reduce suicidality in a group of patients with personality disorders. (Note: One small-sample study in fact suggested that mianserin may be associated with an increased risk of suicide.)

The MAOIs, on the other hand, seem to be effective at stabilizing affective functioning in some patients with BPD. Interestingly, the presence of borderline traits in patients with atypical depression, which is defined operationally as the combination of mood reactivity with reversed (atypical) neurovegetative symptoms, leaden fatigue, or rejection sensitivity, predicts that phenelzine may outperform imipramine. In patients labeled as hysteroid dysphorics, many of whom have traits consistent with personality disorders, phenelzine was shown to improve mood reactivity, problems with being alone, and rejection sensitivity. In another study, both patients and physicians considered tranylcypromine to be helpful for depression or rejection sensitivity.

Lithium, as noted in section III.B, has been shown to be useful in reducing emotional lability among a group of young women diagnosed with emotionally unstable character disorder. Surprisingly, in view of its effectiveness in bipolar disorder, no study has yet demonstrated a strong effect of carbamazepine on affective instability, although, in one study, a few trial noncompleters did rate themselves as experiencing less rejection sensitivity while taking carbamazepine.

D. Anxiety

This very nonspecific symptom, has been treated with many classes of medications. Benzodiazepines, antipsychotic agents, antidepressants, and carbamazepine all appear to have had beneficial effects in some patients. Although many patients with generalized anxiety disorder respond well to benzodiazepines, a situation of greater complexity exists with anxious patients who have personality disorders and who also manifest aggressive or impulsive behaviors. In one study, alprazolam (mean daily dose, 4.7 mg) was associated with marked increases in self-destructive behavior in an outpatient group of women diagnosed with BPD and having a history of such behavior; however, in that study, a small number of patients rated alprazolam as beneficial. Another report noted an improvement of anxiety in three patients with BPD treated with moderate doses of alprazolam (0.5 to 1 mg, four times a day).

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Avoidant personality disorder, in which anxiety is invariably prominent, has been compared with social phobia, a phenomenologically overlapping axis I disorder. Avoidant traits in patients with social phobia may respond to alprazolam, and anxiety in social phobia has also been successfully treated with MAOIs, clonazepam, or buspirone. By analogy, any of these medications merits consideration for the treatment of anxiety in patients with personality disorders. The potential for behavioral disinhibition from benzodiazepine use suggests caution, particularly when a history of self-injurious behavior is present.

An anecdotal report of patients with avoidant personality disorder made note of a reduction of social anxiety and an increased sense of well-being with tranylcypromine, phenelzine, or fluoxetine. Anxiety has also responded well to MAOIs in atypical depressive and hysteroid dysphoric patients, many of whom have personality disorder features. In a treatment study using tranylcypromine, patients with BPD rated their anxiety as improved. One authority hypothesized that the somatic components of anxiety are particularly responsive to MAOIs, whereas psychic anxiety may respond preferentially to benzodiazepines.

Antipsychotic agents are known to have a nonspecific anxiety-reducing or calming effect, yet they are not frequently prescribed for this purpose, perhaps because of concerns about acute and long-term side effects. Nevertheless, a reduction of anxiety has been repeatedly demonstrated in patients with BPD and schizotypal personality disorder who are receiving low doses of neuroleptics, including loxapine, chlorpromazine, haloperidol, thiothixene, trifluoperazine, and thioridazine. When the anxiety is accompanied by a thought disorder, the use of a low dose of an antipsychotic agent may be especially appropriate.

Lithium has not been shown to reduce anxiety in personality disorder patients. Carbamazepine and gabapentin were each rated as beneficial in separate small-sample studies. Table 13.3 summarizes some potentially useful pharmacotherapeutic interventions for treating symptom dimensions in patients with personality disorders.

IV. Caveats

The use of medications always carries with it a risk of untoward outcomes. Recognition of this is particularly important in patients with personality disorders for a number of reasons. In contrast to the treatment of mood disorders, psychosis, or anxiety disorders, the empiric basis of pharmacotherapeutic recommendations regarding personality disorders is more limited. The diagnostic specificity of these disorders is low, and treatment recommendations are only beginning to address the dimensions of behavior rather than the diagnostic categorization. Their chronicity entails the possibility of a need for extended pharmacotherapy. Because of their ego-syntonic nature, the personality disorders are construed by some to be lifestyle choices rather than as diseases requiring treatment; this complicates the clinician's attempts to differentiate the normal from the abnormal. Some clinicians view the effects of medications as potentially cosmetic. In this view, medications can have positive effects that enhance already adequate functioning and that move the patient toward a more desirable state. The act of prescribing a medication to enhance a desirable quality rather than to alleviate a disturbing one is a dramatic alteration of the current role of pharmacotherapy (i.e., treating dysfunction, distress, or disease). Such a reframing of pharmacotherapy, which has already taken place among those who advocate so-called smart drugs (i.e., those reputed to enhance intelligence) or prosexual drugs (i.e., those reputed to enhance sexual performance), has far-reaching implications.

No medication currently carries a United States Food and Drug Administration-approved indication for the treatment of personality disorders or their common traits. As Appendix I discusses, the clinician must follow several important steps when he or she makes a decision to prescribe a medication for a nonapproved

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indication, including complying with the requirement that the patient understands that the medication use in this role is off label and innovative.

TABLE 13.3. SOME POSSIBLE PHARMACOTHERAPIES FOR DIMENSIONS OF PERSONALITY PATHOLOGYa

Symptom Cluster Suggested First-Line Medications Suggested Second-Line Medications Use with Caution or Not at All
Cognitive and perceptual impairment (e.g., transientpsychotic symptoms, distractibility, thought slippage, suspiciousness) Antipsychotic agents
   Olanzapine, 2.5 10 mg/d
   Haloperidol, 2 6 mg/d
   Clozapine, 25 100mg/d
None are known Psychostimulants (may exacerbate symptoms)
Impulsive symptoms (self-injurious behavior, suicidal behaviors) Mood-stabilizing anticonvulsants
   Divalproex sodium, 50 100 g/db
   Lamotrigine, 75 300 mg/d
   Carbamazepine, 4 12 g/d
Serotonergic agents
   Fluoxetine, 5 80 mg/d
   Sertraline, 25 200 mg/d
   Citalopram, 5 80 mg/d
   Venlafaxine, 25 300 mg/dc
Antipsychotic agents
   Haloperidol, 2 6 mg/d
Psychostimulants
   Dexedrine, 5 10 mg t.i.d.
   Methylphenidate, 5 15 mg t.i.d.
Benzodiazepines (may exacerbate impulsivity or self-injurious behavior)
Mood symptoms (instability, rejection sensitivity, dysphoria, related sleep disturbances) Mood-stabilizing anticonvulsants
   Divalproex sodium, 50 100 g/d
   Lamotrigine, 75 300 mg/d
Serotonergic agents
   Fluoxetine, 5 80 mg/d
   Sertraline, 25 200 mg/d
   Citalopram, 5 80 mg/d
Antipsychotic agents
   Olanzapine, 2.5 10 mg/d
   Haloperidol, 2 6 mg/d
Tricyclic antidepressants (may exacerbate mood instability)
Anxious symptoms (free-floating, panic, or obsessive anxiety) Serotonergic agents
   Fluoxetine, 5 80 mg/d
   Sertraline, 25 200 mg/d
   Citalopram, 5 80 mg/d
   Venlafaxine, 25 300 mg/dc
Mood-stabilizing anticonvulsants
   Divalproex sodium, 50 100 g/d
   Lamotrigine, 75 300 mg/d
Antipsychotic agents
   Haloperidol, 2 6 mg/d
   Olanzapine, 2.5 10 mg/d
Nonbenzodiazepine anxiolytics
   Buspirone, 5 20 mg t.i.d.
MAOIs (may be associated with unacceptable risks)
Benzodiazepines (may be associated with risk of misuse)
Abbreviations: MAOIs, monoamine oxidase inhibitors; t.i.d., three times a day.
aThese recommendations are based on research with patients primarily diagnosed with borderline personality disorder and on the authors' clinical experiences.
bNote that, for some agents, concentration ranges are given.
cExperience is insufficient to provide dosage ranges for the venlafaxine XR formulation, but use of the XR formulation may be indicated once a dosage has been established for the patient.

The actual effects of medications on personality disorders are often modest. The degree of benefit may be enough to allow improved functioning, better tolerance of affects, or fuller engagement in psychosocial treatment. Medication in this context is rarely, if ever, curative. One should note, however, that patients may perceive subjective effects that they consider quite significant, even when effects only of a lesser magnitude are observed by blind evaluators. Clinical experience suggests that, in some instances, the medication effects on personality traits may dissipate over a period of months. Whether this decremental change, when it occurs, results from tolerance or adaptation to medication, nonadherence, use of concomitant medications, alcohol or substance abuse, or other factors is not known.

Some medications advocated for treating personality disorder traits are abusable. For example, psychostimulants that may provide significant benefit to an individual affected by ADHD may also provide a greater sense of well-being to patients with BPD without ADHD. Some patients who have heard or read about ADHD may have self-diagnosed a learning disability, which may more truly reflect a wish to function at a level higher than he or she has currently attained. Such a patient might be at risk for psychostimulant abuse.

Benzodiazepines also carry an abuse risk in some patients (see Chapters 9 and 14), in addition to their previously mentioned potential for infrequently causing behavioral disinhibition. When taken in overdose amounts in conjunction with other central nervous system depressants, they may contribute to untoward outcomes. Many other medications are even more dangerous in overdosage (e.g., MAOIs; see Chapter 3).

Adverse physical effects can occur with all agents discussed here. Antipsychotic agents are particularly prone to causing intolerable side effects, including weight gain, sedation, erectile dysfunction, or akathisia. Tardive dyskinesia is a potential long-term hazard. Other medications, such as carbamazepine and lithium, require careful periodic monitoring to reduce the risk of toxic effects. Lamotrigine must be prescribed and monitored with awareness of the potential for serious adverse dermatologic and systemic reactions.1

Adverse psychologic effects can also be seen, such as the unpleasantly overtranquilized or oversedated effect that some patients experience even with low doses of antipsychotic agents; the anxious, agitated, or paradoxically apathetic states sometimes seen with proserotonergic antidepressants; the increased self-injurious or disinhibited behavior occasionally seen during benzodiazepine use; the confusion, agitation, or hostility that has occasionally been seen in patients receiving amitriptyline; and the melancholia-like depressive states that have been observed in some patients taking carbamazepine or thioridazine.

In planning treatment and discussing objectives with a patient, emphasizing the fact that, as yet, no adequate long-term studies of medication effects on personality have been conducted is valuable. The stability of any beneficial effects, the relapse rates upon discontinuation, and the incidence of long-term adverse effects remain unknown.

V. Assessment of Patients for Treatment

Evaluating the patient with a personality disorder for pharmacotherapy differs in several respects from assessing a patient with an axis I disorder. The symptoms of personality disorders are chronic and ego syntonic, blurring the distinction between normal and pathologic. Many of the personality disorder traits of greatest interest to the clinician wax and wane over time in relationship to such variables as the season, the menstrual cycle, contemporaneous stressors, and the availability of supportive relationships, thus necessitating the

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devotion of careful attention to longitudinal functioning. Comorbid axis I syndromes also may be present. Posttraumatic stress disorder, a particularly complex condition for multimodal treatment, is especially important to identify (see Chapters 14 and 27). Mood disorders, anxiety disorders, and psychotic disorders are among other commonly comorbid axis I conditions. The assessment process needs to unfold slowly enough to facilitate information gathering from the patient, a significant other, friends, relatives, and previous caregivers.

The identification of treatment-responsive target symptoms or dimensions requires careful inquiry and tactful negotiation as part of a working alliance. Many patients seeking pharmacotherapy have had prior medication trials. These must be reviewed with attention to their appropriateness for the target symptoms under consideration, the adequacy of dosage and duration, and issues of adherence. To enhance the likelihood of adherence and efficacy, the clinician must thoughtfully inform the patient about potential side effects, the expected duration of treatment, any interactions of the medication with foods or other drugs, the procedure for dealing with missed doses, and the safety or lack thereof from abrupt discontinuation of the medication. Helping the patient conceptualize the way in which pharmacotherapy will complement any other ongoing treatments is also useful.

VI. Treatment Integration: The Psychodynamics of Pharmacotherapy

The pharmacotherapy of personality disturbances offers a modest but significant opportunity to alleviate a spectrum of targeted behavioral disturbances and to promote greater stability. Medications, however, must be a component of a more comprehensive treatment plan that includes other psychosocial interventions, such as individual or group psychotherapy and inpatient care as needed.

The psychodynamic features of the pharmacotherapy relationship should not be overlooked. Even a treatment relationship that is primarily medication oriented has psychotherapeutic elements and exists within a psychodynamic framework. Without attention to elements such as transference (see Chapter 1), pharmacotherapy may have reduced value. As in all therapeutic relationships, a working alliance must be established to allow the treatment to proceed with greatest effectiveness. This pharmacotherapeutic alliance may be tested or strengthened when defining the goals for treatment and discussing side effects, the potential for abuse by the particular patient, or the clinician's availability for the resolution of medication-related and non medication-related difficulties. In delineating the behavior chosen for modification, the clinician can frame the targeted symptom tactfully by identifying it as an alternative that is pursued with some ambivalence within a stressful context (e.g., When you are overly stressed, you sometimes have trouble containing an urge to react with anger, even when you know that other ways of behaving would more likely help your situation ). This approach can be viewed as a form of self-psychopharmacology analogous to the self-psychology used by patients to protect themselves from unbearably disruptive injuries to their self image or sense of self that occur in treatment, as well as in other life situations. Attention to the therapeutic alliance also involves a number of practical matters (e.g., consistency, availability, willingness to discuss and to explain alternatives). The last is particularly important because the use of medications for treatment of personality disorders per se is not among the indications approved by the United States Food and Drug Administration.

The clinician must also be aware that any alliance may fluctuate and may reflect vacillations in the patient's internal state and relationships. At one time, the clinician may be idealized and at another time devalued and hated. Attempting to maintain consistency and stability throughout these fluctuations and to convey a secure presence and a willingness to remain available while continuing to set appropriate limits is important. Sustaining the alliance over time is often a critical factor in outcome, because multiple medication trials may be necessary and these may be accompanied by unexpected side effects, disappointing therapeutic effects, and frequent dosage adjustments.

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Any relationship carries transference elements. Providing medication to a patient may intensify aspects of transference, particularly when patients have expectations and fantasies about the medication(s). Patients' responses vary greatly, however, and a variety of transference reactions may be seen, sometimes in sequence. A common response is for the patient to adopt an idealizing, positive transference toward the prescribing clinician, especially early in treatment when hope abounds. The prescribing clinician may, in fact, be an authoritative and knowledgeable figure, who presents a coherent and nonjudgmental explanation of the patient's difficulties and who seems not to confront the patient with a need to look inward or to face painful past and current experiences. Medication, which some may view with awe and suspicion, may initially be welcomed as a powerful ally. Unfortunately, the inconsistent and sometimes limited results from medication use within the context of long-standing and maladaptive personality traits may be disappointing to some patients, who, after an initial period of significant symptom reduction, may then feel even worse, possibly leading to increased despair and anger. An additional hazard of the initially positive transference toward the prescribing clinician is a concurrent devaluation of any other ongoing treatments, including psychotherapy. The psychotherapist, whose values may stress self-knowledge and long-term dynamic exploration and understanding rather than what he or she views as a quick fix from medication, may be toppled from a primary role in the patient's treatment life and may be relegated to a devalued or resented role. This splitting, if it is unrecognized, may undermine the overall treatment plan.

Some patients seek pharmacotherapy out of a sense of pessimism about their psychotherapy. Others may see medications as agents of control or repression. Still others may experience the taking of pills as a form of identification with an ill relative. Pill taking also can become a way of acting out feelings about a prescribing clinician (e.g., they can be discarded or ingested in excess quantity). Alternatively, medication can be viewed as a comforting transitional object that symbolically represents the committed involvement of the concerned clinician.

Motivations for prescribing medications also deserve attention. Countertransference feelings need to be recognized and understood. Both the psychotherapist and the prescribing clinician must remain alert to countertransferential discouragement, particularly when they are the same person, and to wishes to help treatment progress more quickly or less painfully, to control the patient, or to give something tangible to the patient during a hopeless or helpless impasse. Lack of awareness of such factors may complicate and confound treatment.

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1Topiramate is another anticonvulsant receiving anecdotal use for some behavioral symptoms, including mood lability and promotion of weight loss in patients with antipsychotic agent-induced or antidepressant-induced weight gain. Confusion and memory impairment not infrequently accompany any beneficial effects.



Manual of Psychiatric Therapeutics Paperback
Manual of Psychiatric Therapeutics: Practical Psychopharmacology and Psychiatry (Little, Browns Paperback Book Series)
ISBN: 0316782203
EAN: 2147483647
Year: 2002
Pages: 37

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