Short-term augmentation of fluoxetine with clonazepam in the treatment of depression: a double-blind study

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.

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.

The patients taking clonazepam improved significantly more during the first 3 weeks of treatment according to ratings on the Hamilton scale (> or =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.

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.