Topiramate for Borderline Personality Disorder?

October 2006

Borderline personality disorder (BPD) occurs in approximately 2% of the population. A majority of patients with BPD (approximately 75%) are female. Many patients with BPD take multiple medications. Drugs are typically used to target specific aspects of the disorder, rather than to "cure" the illness. For example, cognitive-perceptual symptoms, such as suspiciousness, paranoid ideation, or temporary hallucinations, can be treated with antipsychotic drugs. Antidepressant agents may be used to treat emotional dysregulation, such as rapid mood shifts, depressive symptoms, anxiety, intense anger, and chronic emptiness.

Displays of aggression and impulsivity are core features of BPD. There has been limited study of anticonvulsants, mostly valproate (Depakote and others) and carbamazepine (Tegretol and others), to suppress these outbursts. Nickel and others tried the anticonvulsant topiramate (Topamax) in men with BPD.1 Forty-two subjects participated in this 8-week, double-blind, placebo-controlled study of topiramate. Starting with a dose of 50 mg/day, patients could take up to 250 mg in a gradually titrated regimen.

Topiramate significantly decreased patients' experience of anger and their readiness to react with anger and direct anger outward. Topiramate was well tolerated. The most common side effects were dizziness, fatigue, somnolence, cognitive impairment, paresthesias, reduced appetite, and weight loss. Patients treated with topiramate lost an average of 5.0 kg (11.1 lb) more than those taking placebo (P < .01).

Initial enthusiasm for topiramate as a mood stabilizer has not been borne out by systematic study. This preliminary trial of topiramate for men with BPD is encouraging but will need to be supported by additional research. Studies in women will be essential, as women make up a majority of patients with this condition. For most adult patients, the well-established side effect of weight loss with topiramate should be a benefit. In addition to medications, two kinds of structured psychotherapy have shown promise for treating BPD. One is a form of cognitive behavioral therapy called dialectical behavior therapy,2 and the other is a psychodynamic, long-term, partial hospitalization program.3 It is reassuring to see more studies targeted to this serious and common condition.

1Nickel MK, Nickel C, Kaplan P, Lahmann C, Mühlbacher M, Tritt K, Krawczyk J, Leiberich PK, Rother WK, Loew TH: Treatment of aggression with topiramate in male borderline patients: A double-blind, placebo-controlled study. Biol Psychiatry 2005;57:495-499.

2Linehan MM, Comtois KA, Murray AM, Brown MZ, Gallop RJ, Heard HL, Korslund KE, Tutek DA, Reynolds SK, Lindenboim N: Two-year randomized controlled trial and follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and borderline personality disorder. Arch Gen Psychiatry 2006;63:757-766.

3Hopkins HS: Borderline personality disorder. Institute for Mental Health Research website archives. Available at Accessed July 18, 2006.