The American Psychiatric Association (APA) has updated its Privacy Policy and Terms of Use, including with new information specifically addressed to individuals in the European Economic Area. As described in the Privacy Policy and Terms of Use, this website utilizes cookies, including for the purpose of offering an optimal online experience and services tailored to your preferences.

Please read the entire Privacy Policy and Terms of Use. By closing this message, browsing this website, continuing the navigation, or otherwise continuing to use the APA's websites, you confirm that you understand and accept the terms of the Privacy Policy and Terms of Use, including the utilization of cookies.

×
Published Online:https://doi.org/10.1176/ajp.155.10.1339

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