A 9-Week Randomized Trial Comparing a Chronotherapeutic Intervention (Wake and Light Therapy) to Exercise in Major Depressive Disorder Patients Treated With Duloxetine

OBJECTIVE: The onset of action of antidepressants often takes 4 to 6 weeks. The antidepressant effect of wake therapy (sleep deprivation) comes within hours but carries a risk of relapse. The objective of this study was to investigate whether a new chronotherapeutic intervention combining wake therapy with bright light therapy and sleep time stabilization could induce a rapid and sustained augmentation of response and remission in major depressive disorder. METHOD: 75 adult patients with DSM-IV major depressive disorder, recruited from psychiatric wards, psychiatric specialist practices, or general medical practices between September 2005 and August 2008, were randomly assigned to a 9-week chronotherapeutic intervention using wake therapy, bright light therapy, and sleep time stabilization (n = 37) or a 9-week intervention using daily exercise (n = 38). Patients were evaluated at a psychiatric research unit. The study period had a 1-week run-in phase in which all patients began treatment with duloxetine. This phase was followed by a 1-week intervention phase in which patients in the wake therapy group did 3 wake therapies in combination with daily morning light therapy and sleep time stabilization and patients in the exercise group began daily exercise. This phase was followed by a 7-week continuation phase with daily light therapy and sleep time stabilization or daily exercise. The 17-item Hamilton Depression Rating Scale was the primary outcome measure, and the assessors were blinded to patients' treatment allocation. RESULTS: Both groups responded well to treatment. Patients in the wake therapy group did, however, have immediate and clinically significantly better response and remission compared to the exercise group. Thus, immediately after the intervention phase (week 2), response was obtained in 41.4% of wake therapy patients versus 12.8% of exercise patients (odds ratio [OR] = 4.8; 95% CI, 1.7-13.4; P = .003), and remission was obtained in 23.9% of wake therapy patients versus 5.4% of exercise patients (OR = 5.5; 95% CI, 1.7-17.8; P = .004). These superior response and remission rates obtained by the wake therapy patients were sustained for the whole study period. At week 9, response was obtained in 71.4% of wake therapy patients versus 47.3% of exercise patients (OR = 2.8; 95% CI, 1.1-7.3; P = .04), and remission was obtained in 45.6% of wake therapy patients and 23.1% of exercise patients (OR = 2.8; 95% CI, 1.1-7.3, P = .04). All treatment elements were well tolerated. CONCLUSIONS: Patients treated with wake therapy in combination with bright light therapy and sleep time stabilization had an augmented and sustained antidepressant response and remission compared to patients treated with exercise, who also had a clinically relevant antidepressant response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00149110.