Maintained superiority of chronotherapeutics vs. exercise in a 20-week randomized follow-up trial in major depression

ObjectiveTo investigate the long-term antidepressant effect of a chronotherapeutic intervention. MethodIn this randomized controlled trial 75 patients with major depression were allocated to fixed duloxetine and either a chronotherapeutic intervention (wake group) with three initial wake therapies, daily bright light therapy, and sleep time stabilization or to a group using daily exercise. Patients were followed 29weeks. We report the last 20weeks, a follow-up phase, where medication could be altered. Patients were assessed every 4weeks. Remission rates were primary outcome. ResultsPatients in the wake group had a statistically significant higher remission rate of 61.9% vs. 37.9% in the exercise group at week 29 (OR=2.6, CL=1.3-5.6, P=0.01). This indicated continued improvement compared with the 9weeks of treatment response (44.8% vs. 23.4%) with maintenance of the large difference between groups. HAM-D-17 endpoint scores were statistically lower in the wake group with endpoint scores of 7.5 (SE=0.9) vs. 10.1 (SE=0.9) in the exercise group (difference 2.7, CL=0.5-4.8, P=0.02). ConclusionIn this clinical study patients continued to improve in the follow-up phase and obtained very high remission rates. This is the first study to show adjunct short-term wake therapy and long-term bright light therapy as an effective and feasible method to attain and maintain remission.