SHORT-TERM AUGMENTATION OF FLUOXETINE WITH CLONAZEPAM IN THE TREATMENT OF DEPRESSION - A DOUBLE-BLIND-STUDY

Objective: Because selective serotonin reuptake inhibitors (SSRIs) req uire 2-4 weeks to reach efficacy, the authors determined whether clona zepam augmentation of fluoxetine is superior to fluoxetine alone at th e beginning of treatment for major depression. Method: Eighty adult ou tpatients with major depression who were rated as ''moderately ill'' o r ''markedly ill'' on the Clinical Global Impression of Severity under went 8 weeks of double-blind, randomized treatment with fluoxetine, 20 mg/day for all patients initially and 40 mg/day if needed after 6 wee ks. One-half of these patients received clonazepam, 0.5 mg h.s. adjust ed to two tablets by day 10 if needed, and the remainder received plac ebo, likewise adjusted. Clonazepam/placebo was gradually discontinued during days 21-33. Efficacy was evaluated by means of the Hamilton Dep ression Rating Scale, the Clinical Global Impression of Improvement, a nd a patient rating of global improvement. Results: The patients takin g clonazepam improved significantly more during the first 3 weeks of t reatment according to ratings on the Hamilton scale (greater than or e qual to 50% improvement) and the clinician- and patient-rated global i mprovement measures (''much'' or ''very much'' improved). Analysis of variance confirmed a significant effect of clonazepam for average Hami lton depression scores. No serious adverse events were found in either treatment group. Taper effects appeared modest and transitory. Conclu sions: Clonazepam augmentation of fluoxetine was superior to fluoxetin e alone in the first 3 weeks of treatment. This strategy may reduce su ffering during early SSRI treatment, may partially suppress SSRI side effects, may increase compliance, and could possibly reduce the risk o f suicide.