Evidence-Based Reviews

Pharmacologic treatment of borderline personality disorder

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Evidence suggests symptom-targeted pharmacotherapy can be beneficial



As psychiatry’s understanding of borderline personality disorder (BPD) grows, the literature clearly describes the seriousness of BPD, as well as these patients’ high utilization of treatment. Pharmacotherapy for BPD remains controversial. The most recent American Psychiatric Association practice guidelines focus on using symptom domains of this heterogeneous illness to guide medication selection, yet when these guidelines were published, there was a lack of data to support this recommendation.1

This article evaluates medications for BPD and emerging data supporting matching medications to BPD symptom domains, with an emphasis on making choices that advance clinical practice. We conclude by reviewing studies of combined pharmacotherapy and dialectical behavior therapy (DBT) and describing how a multidisciplinary team approach can enhance BPD treatment.

Early research

Early studies of pharmacotherapy for BPD began after the development of the Diagnostic Interview for Borderlines2,3 and DSM-III criteria for BPD.4 Researchers recruited patients who fulfilled the diagnostic criteria; however, these participants’ symptom profiles were highly heterogeneous. Although such studies can be useful when starting to test new treatments—especially if they are able to show efficacy over placebo or explore safety—they are less helpful in guiding clinical practice.

During the 1980s, low doses of first-generation antipsychotics were evaluated based on hypotheses that BPD was related to schizophrenia. Case series5 and placebo-controlled trials6,7 pointed to symptom reduction over time and greater than placebo for BPD patients. Interestingly, in a small study of BPD inpatients, Soloff et al8 compared the first-generation antipsychotic haloperidol to amitriptyline and found amitriptyline led to symptom worsening in some patients. Cowdry and Gardner9 compared alprazolam, carbamazepine, trifluoperazine, and tranylcypromine in a double-blind, placebo-controlled crossover trial of 16 female BPD outpatients. They found antipsychotics were not useful. Further, the study found behavioral disinhibition when a benzodiazepine (alprazolam) was used alone in impulsive patients.

These studies provided a basis for the idea that medications could help reduce BPD symptoms. However, some early investigators noted that antipsychotics’ side effects led some patients to discontinue treatment.6

Next-generation studies

Antidepressants. Interest in exploring pharmacologic treatments for BPD diminished after the early efficacy trials. Several events led to a reemergence of this interest, including the FDA’s approval of the selective serotonin reuptake inhibitor fluoxetine for depression in 1987. Some investigators hypothesized fluoxetine’s antidepressant properties could help treat BPD symptoms and perhaps the serotonin reuptake action could diminish impulsivity.10 Case series and a double-blind, placebo-controlled trial11 demonstrated fluoxetine’s efficacy in BPD. In 1 study, Salzman et al12 found fluoxetine’s greatest impact was on “anger,” a major affective dimension of BPD.

Mood stabilizers. When valproic acid emerged as a successful treatment for bipolar disorder, researchers turned their attention to mood-stabilizing anticonvulsants for BPD. Numerous case series and controlled trials provided evidence of its efficacy.13,14 This was the first time subtypes of BPD patients were tested prospectively—with the hypothesis that the mood-stabilizing anticonvulsants would diminish impulsivity and aggression. The positive results of Hollander et al13 and Frankenburg and Zanarini14 in assessing divalproex in BPD patients with bipolar II disorder has implications for targeted treatment (discussed below).

Newer antipsychotics. The introduction of second-generation antipsychotics (SGA) led some researchers to explore whether these agents could decrease BPD symptoms. Case series15 and some (but not all) placebo-controlled trials have demonstrated benefit from SGAs such as olanzapine,16-18 aripiprazole,19 and quetiapine.20,21 Initial research on risperidone22 and ziprasidone also suggested efficacy for BPD. Two placebo-controlled studies of olanzapine examined which symptom groups were most helped; each reported a broad effect.16,17 However, not all studies of SGAs for BPD patients have been positive.18 Further, metabolic side effects have been noted for several SGAs, including olanzapine.18

Omega-3 fatty acids. Some studies examining omega-3 fatty acids have sparked an ongoing interest in this compound. In an 8-week, double-blind, pilot study of 30 women with BPD, Zanarini23 found omega-3 fatty acids demonstrated efficacy over placebo.

Targeted treatment

Most studies of BPD pharmacotherapy have used a classic clinical trial design, which does not easily translate into recommendations regarding medication selection for individual patients, especially those with BPD and comorbid illnesses. Also, existing trials have not fully explored starting doses, and no maintenance studies have been published. Therefore, many clinical application questions remain unresolved. However, some early treatment recommendations are supported by recent meta-analyses that demonstrate effects of medication classes for specific symptom domains.


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