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.