A double-blind, randomized, controlled trial of fluoxetine plus quetiapine or clomipramine versus fluoxetine plus placebo for obsessive-compulsive disorder.
Obsessive-compulsive disorder patients who do not improve sufficiently after treatment with a selective serotonin reuptake inhibitor might improve further if other drugs were added to the treatment regimen. The authors present a double-blind, placebo-controlled trial comparing the efficacy of adding quetiapine or clomipramine to a treatment regimen consisting of fluoxetine. Between May 2007 and March 2010, a total of 54 patients with a primary diagnosis of obsessive-compulsive disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and a current Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of at least 16, the score having dropped by less than 35% after fluoxetine monotherapy, were allocated to 1 of 3 arms (n = 18 per arm): quetiapine + fluoxetine (≤200 and ≤40 mg/d, respectively), clomipramine + fluoxetine (≤75 and ≤40 mg/d, respectively), or placebo + fluoxetine (≤80 mg/d of fluoxetine). Follow-up was 12 weeks. The Y-BOCS scores were the main outcome measure. No severe adverse events occurred during the trial, and 40 patients (74%) completed the 12-week protocol. The Y-BOCS scores (mean [SD]) were significantly better in the placebo + fluoxetine and clomipramine + fluoxetine groups than in the quetiapine + fluoxetine group (final: 18 [7] and 18 [7], respectively, vs 25 [6], P < 0.001) (reduction from baseline: -6.7 [confidence interval {CI}, -9.6 to -3.8; and -6.5 [CI, -9.0 to -3.9], respectively, vs -0.1 [CI, -2.9 to 2.7], P < 0.001; number needed to treat = 2.4). The clomipramine-fluoxetine combination is a safe and effective treatment for fluoxetine nonresponders, especially those who cannot tolerate high doses of fluoxetine. However, the period of monotherapy with the maximum dose of fluoxetine should be extended before a combination treatment strategy is applied.
Department & Institute of Psychiatry, Hospital das Clínicas, University of São Paulo School of Medicine, University of São Paulo, São Paulo, SP, Brazil. julianabelo.diniz@gmail.com
Juliana Belo
JB
Diniz
Roseli Gedanke
RG
Shavitt
Victor
V
Fossaluza
Lorrin
L
Koran
Carlos Alberto de Bragança
CA
Pereira
Euripedes Constantino
EC
Miguel
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002997:Clomipramine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D000069348:Quetiapine Fumarate; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D014150:Antipsychotic Agents; D002997:Clomipramine; D003987:Dibenzothiazepines; D005473:Fluoxetine; D000069348:Quetiapine Fumarate; D017367:Selective Serotonin Reuptake Inhibitors