A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder

Objectives: To evaluate the efficacy and safety of trazodone prolonged release compared with paroxetine in the treatment of patients with major depression. Research design and methods: A total of 108 patients aged 20-68 years were enrolled in this multicentre, double-blind, double-dummy, randomised, paroxetine-controlled study. Each patient received 3 days single-blind placebo treatment followed by 6 weeks double-blind treatment with either trazodone prolonged release 150-450 mg/day (n = 55) or paroxetine 20-40 mg/day (n = 53). Outcome measures: Efficacy was evaluated by the rate of patients responding to each treatment and considered to be in remission, and by mean changes from baseline in the Hamilton Depression Rating Scale Scores (HAM-D), Montgomery Asberg Depression Rating Scale Scores (MADRS), and Clinical Global Impression (CGI) - Severity and Global Improvement scores. Time to onset of efficacy and safety were assessed. Results: Trazodone and paroxetine were equally effective at reducing symptoms of depression and promoting remission. Onset of efficacy was slightly faster for patients treated with paroxetine. Overall, there were no significant differences between the groups at endpoint in efficacy measures, and in percentage of responders (> 85%) or patients in remission (> 65%). Sleep disorders (HAM-D subset) were significantly less evident for patients in the trazodone group at the end of the study (p < 0.05). Adverse drug reactions were reported by 35% of trazodone-treated patients (mainly of the nervous system) and 26% of paroxetine-treated patients (mainly gastrointestinal), although none was considered to be serious. Conclusions: This study showed that after a 6-week period trazodone and paroxetine are not different in reducing the symptoms of depression and, in many patients, in producing the remission of the illness. The known divergence in tolerability profile of the two medications, related to their differing pharmacological properties, was also confirmed. Trazodone may be of advantage in depressed patients with sleep difficulties.