Resolution of sleepiness and fatigue: a comparison of bupropion and selective serotonin reuptake inhibitors in subjects with major depressive disorder achieving remission at doses approved in the European Union

J Psychopharmacol. 2014 Feb;28(2):118-24. doi: 10.1177/0269881113514878. Epub 2013 Dec 18.


Unlike selective serotonin reuptake inhibitors (SSRIs), bupropion may be classified as a dual noradrenaline and dopamine reuptake inhibitor, a difference with potential implications for the treatment of residual sleepiness and fatigue in major depressive disorder (MDD). Post-hoc analysis of subjects with remitted MDD was performed on data pooled from six double-blind, randomized trials comparing the European Union (EU)-approved dose of ≤300 mg/day bupropion with SSRIs (sertraline, paroxetine or escitalopram) for the resolution of sleepiness and fatigue. Hypersomnia score was defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items 22, 23, and 24; fatigue score as HDRS item 13 score; and remission as HDRS-17≤7. Similar proportions of bupropion- and SSRI-treated subjects achieved remission at study endpoint (169/343, 49.3% vs 324/656, 49.4%; last observation carried forward (LOCF), p=0.45). Fewer bupropion-treated remitters had residual symptoms of sleepiness (32/169, 18.9% vs 104/324, 32.1%; p<0.01) and fatigue (33/169, 19.5% vs 98/324, 30.2%; p<0.05). Bupropion-treated remitters also showed greater improvement (mean change from baseline) in sleepiness (p<0.05) and fatigue scores (p<0.01) at endpoint: benefits were evident from week 2 for sleepiness (p<0.01) and week 4 for fatigue (p<0.01). Bupropion treatment at the EU-approved dose of ≤300 mg/day may offer advantages over SSRIs in the resolution of sleepiness and fatigue in remitted MDD patients.

Keywords: Bupropion; fatigue; major depressive disorder; remission; sleepiness.

Publication types

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

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Bupropion / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • European Union
  • Fatigue / prevention & control*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sleep Wake Disorders / prevention & control*


  • Antidepressive Agents, Second-Generation
  • Serotonin Uptake Inhibitors
  • Bupropion