title: Effects of risperidone augmentation in patients with treatment-resistant depression: Results of open-label treatment followed by double-blind continuation.
abstract: Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17< or =7 or CGI-S < or = 2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p = 0.05); relapse rates were 56.1 and 64.1%, respectively (p < or = 0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.
authors.affiliation: Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. mark.rapaport@cshs.org
authors.forename: Mark Hyman
authors.initials: MH
authors.lastname: Rapaport
authors.forename: Georges M
authors.initials: GM
authors.lastname: Gharabawi
authors.forename: Carla M
authors.initials: CM
authors.lastname: Canuso
authors.forename: Ramy A
authors.initials: RA
authors.lastname: Mahmoud
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Bossie
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Turkoz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lasser
authors.forename: Amy
authors.initials: A
authors.lastname: Loescher
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouhours
authors.forename: Fiona
authors.initials: F
authors.lastname: Dunbar
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D015283:Citalopram / Q000009:adverse effects; D003863:Depression / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D016016:Proportional Hazards Models; D018967:Risperidone / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D015283:Citalopram; D018967:Risperidone; D017367:Selective Serotonin Reuptake Inhibitors