A multistage chronobiologic intervention for the treatment of depression: a pilot study

J Affect Disord. 2009 Aug;116(3):201-7. doi: 10.1016/j.jad.2009.01.015. Epub 2009 Feb 20.


Background: Most antidepressant medications in current use have several disadvantages: a delayed therapeutic effect, side effects, stigmatization and concerns about safety for the developing fetus during pregnancy. Several chronobiologic techniques which are free of these disadvantages were proposed as an alternative. The current article reports the design and the initial outcome results of a new chronobiologic multistage intervention (CMI) that is comprised of the following techniques: (i) partial sleep deprivation during the second half of the night (wake therapy--WT), (ii) medium (green) wavelength light in combination with dawn simulation (DS), (iii) bright light therapy (BLT), and (iv) sleep phase advance (SPA).

Methods: The study was conducted as a set of 12 single-case designs with moderate-to-severe depressive volunteering patients. Depression, anxiety and tension measurements were taken on a daily basis beginning with a baseline measurement (T0), followed by a set of four consecutive morning measurements during the therapeutic intervention (T1-T4),and with a final measurement carried out at the end of 4 weeks of follow-up (T5).

Results: A clinically significant rapid improvement of the depressive symptoms was demonstrated and maintained for at least 4 weeks after the end of the intervention. No dropouts or compliance difficulties were observed. Patient satisfaction was high, and other than having to sleep for four nights at the Research and Development Unit, participants were not inconvenienced by the nature of the therapeutic design. Sleepiness in the late afternoon hours was reported by several of the participants, but did not reach a level that interfered with their ability to function. Levels of tension did not show a consistent improvement along the intervention procedure and were not maintained in follow-up. There was some unexpected improvement in the level of anxiety that persisted at follow-up. This latter finding requires further validation by additional studies.

Conclusions: These initial findings showed the procedure to be effective and well tolerated. It affords many advantages, such as the achievement of a rapid response, no extinction of the therapeutic effect after 4 weeks of follow-up, safety, high patient compliance and cost effectiveness. These encouraging results warrant validation in further randomized controlled clinical trials.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anxiety / diagnosis
  • Anxiety / epidemiology
  • Anxiety / therapy
  • Chronotherapy / methods*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Patient Satisfaction
  • Phototherapy
  • Pilot Projects
  • Severity of Illness Index
  • Sleep Deprivation / epidemiology
  • Sleep Deprivation / therapy
  • Young Adult