Sequential improvement of anxiety, depression and anhedonia with sertraline treatment in patients with major depression

Objective: To establish the therapeutic effect profile of sertraline in major depression. It was hypothesized that the antidepressant effect of sertraline showed three phases: Phase 1 where improvements in anxiety are most pronounced; Phase 2 where the greatest improvements are in depressive symptoms; and Phase 3 where the symptoms of anhedonia show the most improvement. To test this hypothesis, an 8-week, open-label study was conducted. Methods: Patients with a major depressive episode (DSM-IV) and a score greater than or equal to 24 on the 17-item HAM-D were enrolled and treated with sertraline 50-150 mg/day. The three symptomatic clusters, anxiety, depression and hedonia, were defined a priori using the Inventory of Depressive Symptomatology-Clinician rated (IDS-C). Periods of interest were: Days 0-7 for anxiety, Days 7-21 for depression and Days 21-56 for anhedonia. Raters were blinded as to the constitution of the clusters and periods. Results: 140 patients were recruited. Improvement in the anxiety cluster of the IDS-C was greatest during Days 0-7, whereas over Days 7-21 most improvement was observed in the depression cluster and the greatest improvement in the hedonic cluster occurred during Days 21-56. Conclusions: These preliminary results are consistent with the hypothesis that the therapeutic effects of sertraline occur in a sequential manner. The symptoms of anxiety improved first, followed by depression and then anhedonia.