The Treatment of Chronic Depression, Part 2: A Double-Blind, Randomized Trial of Sertraline and Imipramine

Background: Chronic depression appears to be a common, frequently disabling illness that is often inadequately treated. Unlike episodic depressions with shorter illness duration, neither acute nor long-term treatment approaches for chronic depression have been well studied.

Method: 635 outpatients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were randomly assigned to 12 weeks of double-blind treatment with either sertraline (in daily doses of 50-200 mg) or imipramine (in daily doses of 50-300 mg). Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment.

Results: Despite high rates of chronicity (mean duration of major depression = 8.9 ± 9.1 years; mean duration of dysthymia = 23 ± 13 years) and high rates of comorbidity, 52% of patients achieved a satisfactory therapeutic response to sertraline or imipramine (by a conservative, intent-to-treat analysis). Approximately 21% of the patients who had achieved a therapeutic response at week 12 had not done so at week 8, confirming the longer time to response in depressions with high chronicity. Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients (6.3% vs. 12.0%).

Conclusion: These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine, although sertraline is better tolerated.