Article SSRI Treatment of Borderline Personality Disorder A Randomized Placebo Controlled Clinical Trial for Female Patients With Borderline Personality Disorder Thomas Rinne M D Ph D Wim van den Brink M D Ph D Luuk Wouters M A Richard van Dyck M D Ph D Objective Selective serotonin reuptake inhibitors SSRIs are recommended for treatment of affect lability impulsivity and aggression in patients with borderline personality disorder This recommendation is based on positive findings in at least 10 open studies and one small double blind study of SSRIs for patients with borderline personality disorder and one study of impulsive aggressive patients with different personality disorders A randomized placebo controlled SSRI study with borderline personality disorder patients however provided inconclusive results because of a large response to placebo It was therefore decided to conduct a new randomized trial with a larger study group Method A double blind placebo controlled randomized trial using the SSRI fluvoxamine for 6 weeks followed by a blind half crossover for 6 weeks and an open follow up for another 12 weeks was conducted with 38 nonschizophrenic nonbipolar female patients with borderline personality disorder The outcome measures were the rapid mood shift impulsivity and aggression subscales from the Borderline Personality Disorder Severity Index Results Fluvoxamine but not placebo produced a robust and long lasting reduction in the scores on the subscale for rapid mood shifts In contrast no difference between the fluvoxamine and placebo groups was observed in the effect on the impulsivity and aggression scores Conclusions In this study fluvoxamine significantly improved rapid mood shifts in female borderline patients but not impulsivity and aggression This latter finding may be due to gender specific differences in impulsivity and aggression Am J Psychiatry 2002 159 2048 2054 P atients suffering from borderline personality disorder constitute a substantial proportion of the consumers of mental health care and exhibit a broad spectrum of symptoms and behaviors affect lability with rapid mood shifts from normal to depressive states distinct irritability or anxiety and impulsive aggressive and parasuicidal behavior A considerable number of studies 1 3 point to the central serotonergic system as a possible target for psychopharmacological intervention for impulsive aggressive and suicidal patients and thus for patients with borderline personality disorder Several open studies 4 9 of selective serotonin reuptake inhibitors SSRIs for small groups of borderline patients suggest that the prescription of an SSRI may be an effective pharmacological strategy to ameliorate the pathology of borderline personality disorder However we know of only one double blind placebocontrolled randomized trial 10 which involved 14 female and eight male borderline patients with mild to moderate symptoms and the results did not confirm the positive results of the open studies because of a high rate of response to placebo After post hoc refinement of the analysis and the introduction of a measure of placebo response statistically significant differences were obtained 2048 with respect to anger and aggression A statistically significant improvement in impulsive aggression was observed after 12 weeks in another double blind randomized SSRI study 11 which included 28 male and 12 female subjects suffering from a variety of impulsive DSM III R personality disorders 13 subjects had borderline personality disorder However the authors warned that the results of this study must be interpreted with caution because of the substantial dropout rate 43 Beyond these promising but controversial results with SSRIs we know of no further double blind placebo controlled studies using larger numbers of borderline patients with severe borderline pathology Moreover on the basis of these findings from SSRI studies SSRI treatment is recommended for borderline personality disorder patients with affect lability impulsivity and aggressiveness 12 13 a strategy also adopted in the practice guideline on borderline personality disorder of the American Psychiatric Association 14 Patients with borderline personality disorder are susceptible to a broad spectrum of axis I disorders such as affective disorders anxiety disorders including posttraumatic stress disorder PTSD eating disorders and Am J Psychiatry 159 12 December 2002 RINNE VAN DEN BRINK WOUTERS ET AL FIGURE 1 Design and Measurement Points in a Randomized Placebo Controlled Study of Fluvoxamine for 38 Women With Borderline Personality Disordera Screening Double Blind Single Blind Open Placebo Fluvoxamine Fluvoxamine 6 weeks 6 weeks 12 weeks Fluvoxamine Fluvoxamine Fluvoxamine Random Assignment Screening Baseline 6 weeks 12 weeks 24 weeks Duration of Fluvoxamine Treatment a Placebo Control Group 0 weeks 6 weeks 18 weeks Experimental Group 6 weeks 12 weeks 24 weeks The initial dose was 150 mg day In cases of insufficient improvement after week 10 the dose could be raised At weeks 12 and 24 11 patients were receiving 200 mg day substance use disorders 15 In all of the SSRI treatment studies of personality disorder patients that we know of current major depressive disorder was an exclusion criterion because of the antidepressive effects of SSRIs Such a criterion however does not allow for the fact that SSRIs are also an effective treatment for many patients with anxiety disorders including PTSD and eating disorders 16 18 Furthermore exclusion of all borderline patients with one or more coexisting axis I disorders would reduce the study group to a marginal group with mild pathology A clinically more relevant research strategy might therefore be a less rigorous exclusion of comorbid axis I disorders and inclusion of them as a covariate in the statistical analysis In addition to the preceding complications the severity of borderline pathology raises some major ethical and practical issues with regard to the use of long term doubleblind placebo controlled treatment Taking this into account we decided to design the study in such a manner that the length of the placebo controlled phase would be kept to a minimum but without the loss of statistical power We believe that the present study includes the largest group N 38 of well diagnosed borderline personality disorder patients with moderate to severe pathology so far studied in a pharmacotherapy trial We conducted a double blind placebo