The antidepressant effect of sertraline is not enhanced by dose titration:results from an outpatient clinical trial

A previous report suggested that 5 weeks of continued treatment with 20 mg of fluoxetine was approximately as effective as double-blind titration to a dose of 60 mg in patients who had failed to respond to 3 weeks of initial treatment at 20 mg. The current study was undertaken to evaluate whether 15 0 mg of sertraline was any more effective than 50 mg in treating depressed patients who were non-responders at 3 weeks. Ninety-one outpatients with DS M-IV major depressive disorder who had a 17-item Hamilton Depression Rating Scale (HAM-D) score greater than or equal to 18 were treated with open lab el sertraline for 3 weeks. Patients who did not achieve remission (defined as 17-item HAM-D total score less than or equal to 8 by week 3) were then r andomized to 5 more weeks of double-blind treatment with either 50 mg of se rtraline or immediate titration to 150 mg of sertraline. Efficacy was asses sed at each visit with the HAM-D, Clinical Global Impressions (CGI)-severit y and improvement scale, and the Hopkins Symptom Checklist. There were no s ignificant between-group differences in clinical or demographic features at baseline for the three treatment groups. After 3 weeks of open-label treat ment, 16 patients were not randomized, of whom II (69%) met responder crite ria. The remaining patients were randomized, double-blind, to 50 mg of sert raline (n = 37; HAM-D = 19.2 +/- 5.0) or 150 mg of sertraline (n = 38; HAM- D = 18.4 +/- 5.0). PROC-Mixed analyses found no significant difference in s lopes for any outcome measure when comparing 50 mg and 150 mg sertraline tr eatment groups. At week 8 (LOCF), the overall remission rate (HAM-D less th an or equal to 8) for 3-week non-responders was 40%, with no statistically significant between-group difference for the 50 mg versus 150 mg doses of s ertraline (P > 0.10). A completer analysis yielded similar results. Adverse events were mostly mild on both doses of sertraline and led to few treatme nt discontinuations. The results suggest that for most patients continued t reatment with 50 mg dose of sertraline yields a rate of antidepressant resp onse that is comparable to what is achieved by dose escalation from 50 mg t o 150 mg of sertraline after 3 weeks of treatment. While some patients clea rly benefit from higher doses, the results of the current study are consist ent with the lack of any evidence for a dose-response curve with sertraline in the treatment of depression. Int Clin Psychopharmacol 16:137-143 (C) 20 01 Lippincott Williams & Wilkins.