Fluoxetine versus trazodone: efficacy and activating-sedating effects.

Background: The efficacy and safety of fluoxetine (N = 65; median sustained dose, 20 mg/day) and of trazodone (N = 61; median sustained dose, 250 mg/day) were compared in a trial in outpatients with major depressive episode. The incidence and temporal patterns of activation and sedation were also assessed.

Method: Men and women who met DSM-III criteria for nonpsychotic major depressive episode (but with a current episode greater than or equal to 4 weeks) and had a 21-item Hamilton Rating Scale for Depression (HAM-D21) score greater than 20 were selected. After single-blind placebo was administered for 1 week, eligible patients were randomized to double-blind fluoxetine or trazodone treatment for up to 6 weeks. Efficacy (HAM-D21, Clinical Global Impressions Scales for Severity and Improvement, Patient Global Impressions Scale for Improvement, Guild Memory Test) and adverse events were evaluated weekly.

Results: The HAM-D21 score improved within both treatment groups (p less than .001). The groups were similar with respect to endpoint mean HAM-D21 improvement. For individual adverse events that developed or worsened during therapy, more fluoxetine-treated patients reported rhinitis and tremor (p less than or equal to .05), while more trazodone-treated patients reported somnolence and dizziness (p less than or equal to .05). More combined events suggesting activation (agitation, anxiety, nervousness, insomnia) were reported with fluoxetine than with trazodone (15.4% vs. 3.3%, p less than or equal to .05), while more combined events suggesting sedation (somnolence, asthenia) were reported with trazodone than with fluoxetine (42.6% vs. 21.5%, p less than or equal to .05). Discontinuation rates for activation and sedation did not differ between treatments. Numerically, more sedation (21.5%) than activation (15.4%) was reported with fluoxetine.

Conclusions: There was little clinical difference between treatments with regard to efficacy and safety. The occurrence and temporal patterns of activation and sedation differed within and between treatments.