Personality disorders have a long history of being difficult to treat. Not many years ago it was felt that they could only be treated by skilled experts in intensive long-term psychotherapy. As our understanding of these disorders has improved with empirical research, so has our vision of what treatments can and should be. Although there will always be patients treated by intensive methods by individual experts over long periods, that is not the only approach now conceptualized. In psychotherapy there is now more emphasis on the team approach used by dialectic behavior therapy that relies on modified cognitive/behavioral techniques. This provides an alternative to psychoanalytic techniques.
Our concept of psychopharmacologic treatment has also changed. At one time it was thought counterproductive to use drugs in the treatment of personality disordered patients at all as it would interfere with psychotherapy. Of course, as with any difficult patient group, clinicians will try whatever might work. This led to the realization that at least in some circumstances in some patients, drug treatment could be beneficial. What we have found, in general, is that we do not have specific drug treatments for categorical personality disorders as we might have, for instance, with major depression or with panic disorder. What we have is an array of drugs that help to some extent with certain symptoms and traits commonly found in personality disorders.
This article examines these pharmacological treatments. It first examines some of the drugs that have been used and some of the evidence for their effectiveness. It then takes the mindset of a clinician and looks at how some symptom clusters might be approached.
EVIDENCE FOR TREATMENT OF PERSONALITY TRAITS FOR DIFFERENT DRUGS
Because they are established as effective in the treatment of psychotic symptoms, traditional neuroleptics have been used extensively to treat paranoia, dissociation, ideas of reference, and illusions in personality disordered patients.
In a double-blind placebo-controlled study comparing low dose haloperidol, tricyclic antidepressant (TCA), and placebo Soloff et al.1 found that patients on haloperidol experienced gains in a number of areas. Improvements were reported in depression, anxiety, anger, hostility, impulsiveness, and paranoia. The superiority of haloperidol was not replicated in a subsequent study that compared it to phenelzine (monoamine oxidase inhibitor [MAOI]) and placebo.2 In this latter study phenelzine produced superior results in the areas of depression, anxiety, anger, hostility, and other measures. Soloff hypothesized that haloperidol might be more effective in more impaired individuals. This was consistent with the conclusions of Goldberg et al.3 who used thiothixene in a double-blind placebo-controlled study and found some usefulness in psychotic symptoms only for severe borderline and schizotypal patients.
Cornelius et al.4 performed a double-blind placebo controlled continuation study comparing haloperidol (neuroleptic), phenelzine (MAOI), and placebo in patients with borderline personality disorder. The purpose of the study was to determine whether patients could receive benefit from drug treatment past the initial crisis stage. Haloperidol lacked strong efficacy, but did reduce irritability beyond the acute treatment phase. When dropout rates are examined, haloperidol was again unimpressive. Mean survival time was 8.4 weeks compared to 13.4 weeks for phenelzine and 17.8 weeks for placebo.
Cowdry and Gardner5 did a double-blind study on 16 women with borderline personality disorder comparing alprazolam (benzodiazepine), carbemazepine (mood stabilizer), tranylcypromine (monoamine oxidase inhibitors), trifluperazine (neuroleptic), and placebo. This was a crossover design where all patients received all five conditions. Although there were some reported gains with trifluperazine in anxiety reduction, suicidality, depression, and sensitivity rejection, 50% discontinued this trial arm due to side effects or exacerbation of symptoms.
Although some gains have been reported using traditional neuroleptics, the results are not impressive after the initial crisis and the dropout rate is high. The literature indicates neuroleptics should be used in low doses and even then there is a high dropout rate. The risk of tardive dyskinesia should always be kept in mind. Neuroleptics seem to be of most use in the most severely ill patients.
The literature on the atypical neuroleptics is not as extensive as that on traditional neuroleptics. There are several trials with clozapine. An open label report by Frankenburg et al.6 on 15 patients with severe borderline personality disorder showed some improvement of psychotic symptoms. The doses were relatively high and there were many side effects. Another study of 12 patients with borderline personality disorder using lower doses of clozapine also found reduced psychotic symptoms and increase in global functioning. There were fewer side effects in this study, most likely due to the lower dose.7 A report on seven severe patients with borderline personality disorder treated with clozapine indicated a significant reduction in self-mutilation.8
Risperdone was shown to reduce psychotic symptoms in seven borderline paitents9 and there are two case reports of decreased self-mutilation.10,11 There are two reports on olanzapine. The first studied 11 patients with borderline personality disorder on olanzapine monotherapy and reports significant reductions in five global ratings.12 A case report indicates decreased selfmutilation behavior.13
The atypical antipsychotics appear to be promising agents, especially for psychotic personality disorder symptoms, although much work remains to be done.
The use of TCAs has been fairly well investigated in borderline personality disorder. Early open label trials showed some benefit.14,15 Later double-blind trials found a modest improvement in some patients treated with amitriptyline; however, there was a paradoxical effect in some patients with an increase in hostility and affective instability.16,17 The paradoxical effects, low efficacy, and side effects (lethality in overdose, weight gain, sedation, and dry mouth) are strong relative contraindications to its use, at least in patients with borderline personality disorder.
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors have been of interest for personality features before the borderline personality diagnosis was widespread. It was hypothesized that MAOI treatment would be useful for an atypical type of depression with extreme rejection sensitivity called hysteroid dyshporia. Leibowitz et al. examined the effects of phenelzine (MAOI), imipramine (TCA), and placebo in this population.18 Phenelzine was superior to imipramine and placebo. Parsons et al. examined a subsample from the study who had maintained mood reactivity while depressed.19 Among these patients there was a response rate of 92% on phenelzine, 35% for imipramine, and 25% for placebo.
In a double-blind placebo study of borderline personality2 Soloff et al. found phenelzine produced superior results compared to a TCA and placebo. This superiority included the areas of depression, anxiety, and hostility. Cowdry and Gardner in their crossover study5 found significant improvement for tranylcypromine in the areas of depression, anger, loneliness, and rejection sensitivity. (These were patients who had comorbid borderline personality and hysteroid dsyphoria and who therefore had extreme rejection sensitivity.)
Monoamine oxidase inhibitors represent a possible treatment of borderline personality traits of affective lability, hostility, and rejection sensitivity. Their use is limited by their lethality in overdose and drug interactions ("beer, wine, cheese reaction") in patients who tend to react suddenly and impulsively.
Selective Serotonin Reuptake Inhibitors
There are now nine double-blind studies on the effect of selective serotonin reuptake inhibitors (SSRIs) on personality traits.20,28 Cocarro et al. examined a population of personality disordered patients without concurrent affective disorder, schizophrenia, or substance abuse.20 Treatment with fluoxetine resulted in sustained reduction of irritability and aggression scores. A study of a normal population treated with paroxetine demonstrated a reduction in hostility and negative affect.21
There are a number of studies of the treatment of personality traits in patients with depressive illness. Fava et al.22 found a general reduction in personality disorder traits treated with paroxetine. Salzman et al.23 studied an outpatient borderline population with anxiety and depressive symptoms, but not major depression. Treatment with fluoxetene resulted in a significant decrease in anger. A treatment study of major depression with sertraline or paroxetine over 24 weeks demonstrated reductions in all three DSM personality clusters.24
Ekselius et al.25 examined the effect of treatment of sertraline and citalopram on the personality status of depressed patients in primary care. Both active treatments reduced the frequency of measured paranoid, avoidant, and dependent personality disorder diagnoses. Reductions of dimensional personality traits were found in most categories. Importantly, the effect of state changes on the outcome was examined. Although the change in state depression did effect the reduction in personality traits, the R2 never exceeded 0.24 (this was in the cluster C personality disorders).
Another report examining the use of paroxetine, fluvoxetine, and fluoxetine indicated a general reduction in personality pathology.26 A large double-blind study of sertraline on dysthymic patients showed a significant reduction in harm avoidance.27 One report examined the effect of paroxetine on chronically suicidal patients who did not have major depression.28 A significant reduction in both personality traits and suicidal behavior was found.
The overall findings indicate that SSRIs can be of significant help in the reduction of personality pathology. This is most notable in the area of irritability and aggression, but may affect much broader areas of personality functioning. The onset can be relatively rapid at 1 to 2 weeks. Dosage ranges are from those used to treat depression up to the dosages used to treat obsessive compulsive disorder.
Lithium. There have been a number of studies of lithium for mood lability in the personality disorders. Early work using the diagnosis emotionally unstable character disorder demonstrated some evidence against mood lability in adolescent girls.29 Lithium was also reported to have efficacy against impulsive aggression in adult criminal subjects30,31 and in delinquent adolescents.32 There is a report of treatment of patients with borderline personality disorder with some positive effects.33
There has been only one double-blind placebocontrolled study. Links et al.34 compared lithium to desipramine in a double-blind crossover study. Therapists rated their patients as more improved on lithium on measures of irritability, anger, and suicidal symptoms.
Overall it appears that lithium may be of use in some patients for impulsive aggressive symptoms. This should be balanced against toxicity in overdoese.
Carbamezepine. There are two double-blind studies of carbamezepine. There is a 1986 study of 16 borderline personality disorder patients (all female) with a history of behavioral dyscontrol.35 The study lasted 33 days and carbamezepine significantly reduced the severity of the dyscontrol. The same authors did a later four drug placebo controlled crossover strudy described earlier.5 This study...
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