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

Acta Psychiatr Scand. 2015 Jun;131(6):446-57. doi: 10.1111/acps.12402. Epub 2015 Feb 17.


Objective: To investigate the long-term antidepressant effect of a chronotherapeutic intervention.

Method: In 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 29 weeks. We report the last 20 weeks, a follow-up phase, where medication could be altered. Patients were assessed every 4 weeks. Remission rates were primary outcome.

Results: Patients 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 9 weeks of treatment response (44.8% vs. 23.4%) with maintenance of the large difference between groups. HAM-D17 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).

Conclusion: In 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.

Keywords: chronotherapy; depressive disorder; light therapy; randomized controlled trial; sleep; sleep deprivation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage*
  • Combined Modality Therapy
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / therapy*
  • Drug Chronotherapy
  • Duloxetine Hydrochloride / administration & dosage*
  • Exercise
  • Exercise Therapy / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Phototherapy / methods*
  • Self-Assessment
  • Sleep / physiology
  • Treatment Outcome


  • Antidepressive Agents
  • Duloxetine Hydrochloride