This post-hoc study examined the effectiveness of the noradrenaline and dopamine reuptake inhibitor (NDRI) bupropion (at European-approved dose levels up to 300mg per day) versus selective serotonin reuptake inhibitors (SSRIs) in the resolution of sleepiness and fatigue in patients with Major Depressive Disorder (MDD).

Data were pooled from six double-blind, randomised MDD trials comparing bupropion (n=662) with an SSRI (n=655). 343 patients dosed with bupropion at 300mg per day or less, were compared with all SSRI-treated patients. Hypersomnia score was defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items 22, 23 and 24. Fatigue score was defined as item 13 score of the HDRS.

A similar proportion of bupropion- and SSRI-treated patients achieved remission at study endpoint (49.3% for bupropion and 49.4% for SSRIs, LOCF, p=0.45, OR = 0.9, 95% CI: 0.69 - 1.18). A smaller proportion of bupropion-remitters had residual symptoms of sleepiness (18.9% vs. 32.1%; p<0.01) and fatigue (19.5% vs. 30.2%; p<0.05) compared to SSRI-remitters. There was greater improvement (mean change from baseline) in sleepiness (p<0.05) and fatigue scores (p<0.01) among bupropion-remitters at endpoint, compared to SSRI-remitters and these benefits were evident from week 2 for sleepiness (p<0.01) and from week 4 for fatigue (p<0.01).

This analysis indicates bupropion treatment (≤300mg per day) offers advantages over SSRIs in the resolution of sleepiness and fatigue in patients who have achieved remission from MDD. These findings support a selective advantage offered by a dual acting dopaminergic/noradrenergic agent over serotonergic based treatment.