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Short-Term Augmentation of Fluoxetine With Clonazepam in the Treatment of Depression: A Double-Blind Study

Objective:Because selective serotonin reuptake inhibitors (SSRIs) require 2–4 weeks to reach efficacy, the authors determined whether clonazepam augmentation of fluoxe­tine is superior to fluoxetine alone at the beginning of treatment for major depression.Method:Eighty adult outpatients with major depression who were rated as "moderately ill" or "markedly ill" on the Clinical Global Impression of Severity underwent 8 weeks of double-blind, randomized treatment with fluoxetine, 20 mg/day for all patients initially and 40 mg/day if needed after 6 weeks. One-half of these patients received clonazepam, 0.5 mg h.s. adjusted to two tablets by day 10 if needed, and the remainder received placebo, likewise adjusted. Clonazepam/placebo was gradually discontinued during days 21–33. Efficacy was evaluated by means of the Hamilton Depression Rating Scale, the Clinical Global Impression of Improvement, and a patient rating of global improvement.Results:The patients taking clonazepam improved significantly more during the first 3 weeks of treatment according to ratings on the Hamilton scale (50% improvement) and the clinician- and patient-rated global improvement measures ("much" or "very much" improved). Analysis of variance confirmed a significant effect of clonazepam for average Hamilton depression scores. No serious adverse events were found in either treatment group. Taper effects appeared modest and transitory.Conclusions:Clonazepam augmentation of fluoxetine was superior to fluoxetine alone in the first 3 weeks of treatment. This strategy may reduce suffering during early SSRI treatment, may partially suppress SSRI side effects, may increase compliance, and could possibly reduce the risk of suicide. Am J Psychiatry 1998; 155: 1339-1345

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