A Preliminary, Randomized Trial of Fluoxetine, Olanzapine, and the Olanzapine-Fluoxetine Combination in Women With Borderline Personality Disorder

Background: The intent of this study was to compare the efficacy and safety of fluoxetine, olanzapine, or the olanzapine-fluoxetine combination (OFC) in the treatment of women meeting criteria for borderline personality disorder (without concurrent major depressive disorder).

Method: We conducted a randomized double-blind study of these agents in female subjects meeting Revised Diagnostic Interview for Borderlines (DIB-R) and DSM-IV criteria for borderline personality disorder. Treatment duration was 8 weeks. Outcome measures were clinician-rated scales measuring depression (the Montgomery-Asberg Depression Rating Scale) and impulsive aggression (the Modified Overt Aggression Scale). Data were collected from August 2001 through March 2003.

Results: Fourteen subjects were randomized to fluoxetine; 16, to olanzapine; and 15, to OFC. Forty-two of these subjects (93.3%) completed all 8 weeks of the trial. Using random-effects regression modeling of panel data of change-from-baseline scores and controlling for time, olanzapine monotherapy and OFC were associated with a significantly greater rate of improvement over time than fluoxetine on both outcome measures. However, it should be noted that fluoxetine treatment led to a substantial reduction in impulsive aggression and severity of depression. Weight gain was relatively modest in all 3 groups but significantly greater in the olanzapine-treated group than in the groups treated with fluoxetine alone or OFC.

Conclusion: All 3 compounds studied appear to be safe and effective agents in the treatment of women with borderline personality disorder, significantly ameliorating the chronic dysphoria and impulsive aggression common among borderline patients. However, olanzapine monotherapy and OFC seem to be superior to fluoxetine monotherapy in treating both of these dimensions of borderline psychopathology.