Melatonin treatment of winter depression following total sleep deprivation: waking EEG and mood correlates

Neuropsychopharmacology. 2005 Jul;30(7):1345-52. doi: 10.1038/sj.npp.1300698.


Patients with winter depression (seasonal affective disorder (SAD)) commonly complain of sleepiness. Sleepiness can be objectively measured by spectral analysis of the waking electroencephalogram (EEG) in the 1-10 Hz band. The waking EEG was measured every 3 h in 16 female SAD patients and 13 age-matched control women throughout a total sleep deprivation of 30 h. Melatonin (or placebo) under double-blind conditions was administered subsequently (0.5 mg at 1700 h for 6 days), appropriately timed to phase advance circadian rhythms, followed by reassessment in the laboratory for 12 h. The increase in EEG power density in a narrow theta band (5-5.99 Hz, derivation Fz-Cz) during the 30 h protocol was significantly attenuated in patients compared with controls (difference between linear trends p=0.037). Sleepiness (p=0.092) and energy (p=0.045) self-ratings followed a similar pattern. Six patients improved after sleep deprivation (> or =50% reduction on SIGH-SAD(22) score). EEG power density dynamics was correlated with clinical response to sleep deprivation: the steeper the build-up (as in controls), the better the improvement (p<0.05). There was no differential effect of melatonin or placebo on any measure; both treatments stabilized the improvement. Overall, patients with winter depression manifest similar wake EEG characteristics as long sleepers or late chronotype with respect to an insufficient build-up of homeostatic sleep pressure. Sleep deprivation was an effective antidepressant treatment for some patients, but evening melatonin was not more efficacious than placebo in sustaining this antidepressant effect.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects*
  • Affect / physiology
  • Case-Control Studies
  • Disorders of Excessive Somnolence / drug therapy
  • Disorders of Excessive Somnolence / etiology
  • Double-Blind Method
  • Electroencephalography / drug effects*
  • Female
  • Humans
  • Linear Models
  • Melatonin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Seasonal Affective Disorder / complications
  • Seasonal Affective Disorder / drug therapy*
  • Sleep Deprivation / complications*
  • Spectrum Analysis / methods
  • Wakefulness / physiology


  • Melatonin