title: A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To examine the efficacy and safety of olanzapine at low and moderate doses for the treatment of borderline personality disorder.
  
  
  METHODS
  In this 12-week randomized double-blind placebo-controlled trial, 451 outpatients aged 18-65 years with DSM-IV borderline personality disorder received olanzapine 2.5 mg/d (n = 150), olanzapine 5-10 mg/d (n = 148), or placebo (n = 153). The trial was conducted from February 2004 through January 2006 at 59 community-based and academic study centers in 9 countries (United States, Italy, Poland, Romania, Turkey, Chile, Peru, Argentina, and Venezuela). The primary efficacy measure was mean change from baseline to last-observation-carried-forward endpoint on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) total score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Modified Overt Aggression Scale, the Global Assessment of Functioning, the Symptom Checklist-90-Revised, and the Sheehan Disability Scale.
  
  
  RESULTS
  An overall mean baseline ZAN-BPD total score of 17.2 (SD = 4.9) indicated moderate symptom severity. Only treatment with olanzapine 5-10 mg/d was associated with significantly greater mean change from baseline to endpoint in ZAN-BPD total score relative to placebo (-8.5 vs -6.8, respectively; P = .010; effect size = 0.29; 95% CI, 0.06-0.52). Response rates (response indicated by ≥ 50% decrease from baseline in ZAN-BPD total score) were significantly higher for olanzapine 5-10 mg/d (73.6%) versus olanzapine 2.5 mg/d (60.1%; P = .018) and versus placebo (57.8%; P = .006). Time to response was also significantly shorter for patients taking olanzapine 5-10 mg/d than for placebo-treated patients (P = .028). Treatment-emergent adverse events reported significantly more frequently among olanzapine-treated patients included somnolence, fatigue, increased appetite, and weight increase (all P values < .05). Mean weight change from baseline to endpoint was significantly greater for olanzapine-treated than for placebo-treated patients (olanzapine 2.5 mg/d: 2.09 kg; olanzapine 5-10 mg/d: 3.17 kg; placebo: 0.02 kg; P < .001). The overall completion rate for the 12-week double-blind treatment period was 65.2% (ie, 64.7% for olanzapine 2.5 mg/d, 69.6% for olanzapine 5-10 mg/d, and 61.4% for placebo).
  
  
  CONCLUSIONS
  Olanzapine 5-10 mg/d showed a clinically modest advantage over placebo in the treatment of overall borderline psychopathology. This advantage in effectiveness should be weighed against the risk of adverse events (particularly weight gain), which were consistent with the known safety profile of olanzapine.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00088036.
authors.affiliation: McLean Hospital, Belmont, MA 02478, USA. zanarini@mclean.harvard.edu
authors.forename: Mary C
authors.initials: MC
authors.lastname: Zanarini
authors.forename: S Charles
authors.initials: SC
authors.lastname: Schulz
authors.forename: Holland C
authors.initials: HC
authors.lastname: Detke
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Fangyi
authors.initials: F
authors.lastname: Zhao
authors.forename: Daniel
authors.initials: D
authors.lastname: Lin
authors.forename: Walter
authors.initials: W
authors.lastname: Deberdt
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kryzhanovskaya
authors.forename: Sara
authors.initials: S
authors.lastname: Corya
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001883:Borderline Personality Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D000077152:Olanzapine; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D001569:Benzodiazepines; D000077152:Olanzapine