Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study

J Affect Disord. 2004 Aug;81(2):173-8. doi: 10.1016/S0165-0327(03)00162-9.


Background: Hypersomnia is a cardinal symptom of seasonal affective disorder/winter depression. This open-label pilot study assessed modafinil, a novel wake-promoting agent, as treatment for seasonal affective disorder/winter depression.

Methods: Total daily modafinil dose was 100 mg (all patients week 1), and 100 mg or 200 mg split dose (weeks 2-8). Efficacy assessments (weeks 1, 2, 5, and 8) included the Structured Interview Guide for the Hamilton Depression (HAM-D) Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression of Change (CGI-C), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS).

Results: Thirteen patients (11 women; mean age, 41 years) were enrolled, 12 were evaluable for efficacy (100 mg dose, five patients; 200 mg dose, seven patients), and nine completed treatment. Modafinil significantly improved winter depression as shown by reductions from baseline in mean SIGH-SAD at week 1 (P<0.01) through week 8 (P<0.001 weeks 2-8) and MADRS total scores from week 2 through week 8 (P<0.01 for all). At week 8, mean SIGH-SAD total score was 17.1 (versus 37.2 at baseline, P<0.001), and mean MADRS total score was 13.3 (versus 26.9 at baseline, P<0.01). Modafinil significantly improved overall clinical condition at all time points (P<0.001). The response rate was 67% on the SIGH-SAD (29 item), HAM-D (21 item), and MADRS, and 100% on eight atypical SIGH-SAD items. Modafinil significantly reduced fatigue (FSS) and improved wakefulness (ESS) from weeks 2 through 8 (P<0.01). Modafinil was well tolerated.

Limitations: This was an open-label, single site study.

Conclusions: Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Modafinil
  • Seasonal Affective Disorder / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Modafinil