Efficacy and tolerability of pharmacotherapies for borderline personality disorder

Borderline personality disorder is a pervasive pattern of instability of interpersonal relationships, affects and self-image, as well as marked impulsivity. Although psychotherapy is needed to attain lasting improvements in a patient's personality and overall functioning, practice guidelines state that pharmacotherapy is indicated to manage state symptoms and trait vulnerabilities. Three psychopathological dimensions are the main targets for pharmacotherapy of borderline personality disorder: affective dysregulation, impulsive-behavioural dyscontrol and cognitive-perceptual symptoms. Guidelines recommend the use of antidepressant agents and mood stabilizers for affective dysregulation and impulsive-behavioural dyscontrol, and antipsychotics for cognitive-perceptual symptoms. This review aims to report and discuss data from clinical trials, reviews and meta-analyses concerning drug efficacy and tolerability in the treatment of borderline personality disorder. Investigations that considered antidepressant agents mainly focused on SSRIs, which are recommended as first-line treatments for affective instability and impulse dyscontrol. Both open-label and randomized controlled studies have been performed, predominantly concerning the efficacy of fluoxetine and fluvoxamine. Other classes of antidepressants, such as TCAs and MAOIs, were investigated as alternative treatments for borderline personality disorder, but the risk of adverse effects and toxicity is a limitation to their use in clinical practice. Increasing amounts of data have recently been collected on the use of mood stabilizers to control mood instability and impulsivity in patients with borderline personality disorder. More substantial data were derived from controlled trials of valproate semisodium, although other drugs such as lithium, carbamazepine, oxcarbazepine and lamotrigine were tested with promising results. Several first-generation antipsychotics were studied in open-label and controlled trials, with good effects on behavioural dyscontrol and psychotic-like symptoms. Selection biases and heterogeneity of drugs and methods somewhat limited the value of these results. More recent investigations have examined atypical antipsychotics, with most of these studies being open-label trials with small sample sizes; however, a few controlled studies have been performed using olanzapine, showing improvements in impulsivity, anger and hostility. In conclusion, a large number of different drugs have been evaluated in the treatment of patients with borderline personality disorder. Initial findings are encouraging for many of these drugs. However, data need to be replicated in further controlled studies with head-to-head comparisons and long-term follow-ups. Many questions remain to be answered.