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April 2009

Medication Treatment for BPD: The Limited Evidence Base
Antipsychotics, especially olanzapine (Zyprexa), may be beneficial in treating borderline personality disorder, but the data are limited and mixed.

Chelation Therapy for Autism?
A study of chelation therapy for autism was stopped due to potential adverse effects.

Varenicline for Smoking Cessation
Varenicline (Chantix) should be used with caution in psychiatric patients attempting to quit smoking.

Minocycline for Schizophrenia: Preliminary Results
The results from an open-label study of minocycline (Solodyn and others) suggest benefit in the treatment of schizophrenia.

In Brief
Modifying risk factors can help prevent dementia; Increased lighting improves cognition in elderly

Medication Treatment for BPD: The Limited Evidence Base

April 2009

Borderline personality disorder (BPD) is characterized by behaviors that can be highly disruptive and costly. It is painful to patients, family members, and associates and causes substantial morbidity and mortality. Psychotherapy is commonly used to treat patients with BPD. For decades, clinicians have also prescribed medications to try to alleviate depression, disruptive behaviors, and other symptoms. Abraham and Calabrese recently reviewed the limited number of double-blind, randomized, controlled trials of medications for patients with BPD.1

Studies have been conducted with the nonselective irreversible monoamine oxidase inhibitor (MAOI) antidepressants tranylcypromine (Parnate) and phenelzine (Nardil), the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Prozac and others) and fluvoxamine (Luvox and others), three tricyclic antidepressants, and mianserin.* Double-blind trials have studied the anticonvulsants divalproex (Depakote and others), carbamazepine (Tegretol and others), topiramate (Topamax), and lamotrigine (Lamictal). Several trials have included first-generation antipsychotics, and the second-generation antipsychotic olanzapine (Zyprexa) has been studied extensively for this indication. Other medications examined include lithium, the benzodiazepine alprazolam (Xanax and others), and in one trial, omega-3 fatty acids.

More BPD patients have been studied systematically in trials involving olanzapine than any other drug. Five trials randomized a total of 100 patients to olanzapine, with uniformly positive findings. Weight gain was a common adverse effect, averaging approximately 3.0 kg (6.7 lb). In a study comparing the olanzapine-fluoxetine combination (Symbyax), fluoxetine alone, and olanzapine alone for patients with BPD, olanzapine was superior to fluoxetine and even to the combination in treating depressive symptoms. A more recent study, not included in Abraham and Calabrese's review, failed to find statistically significant benefit from olanzapine over placebo in 314 patients with BPD.2 Olanzapine-treated subjects gained an average of 2.86 kg (6.36 lb), and more than one-third had a greater than 7% increase in body weight. Olanzapine also caused elevated prolactin levels.

Among antidepressants, benefits from SSRIs have been modest. The three trials involving MAOIs have been largely positive. First-generation antipsychotics, some anticonvulsants, and lithium may improve some symptoms in some patients with BPD, but the evidence is limited at best.

Individual patients with BPD may benefit from medications of diverse pharmacologic classes for varying symptoms. Clinical wisdom suggests that the most reliable effects against depression and rage come from antipsychotics, typically at low doses. Conceivably, all antipsychotics—both first- and second-generation—may be comparable. But for now, the mixed evidence lends some support for the efficacy of olanzapine in BPD patients. As always, potential benefits must be weighed against the considerable burden of side effects.

*Not available in the United States.

1Abraham PF, Calabrese JR: Evidenced-based pharmacologic treatment of borderline personality disorder: A shift from SSRIs to anticonvulsants and atypical antipsychotics? J Affect Disord 2008;111:21-30.

2Schulz SC, Zanarini MC, Bateman A, Bohus M, Detke HC, Trzaskoma Q, Tanaka Y, Lin D, Deberdt W, Corya S: Olanzapine for the treatment of borderline personality disorder: Variable dose 12-week randomised double-blind placebo-controlled study. Br J Psychiatry 2008;193:485-492.