Consistent Differential Effects of Bupropion and Mirtazapine in Major Depression
Abstract
Background
Patients with major depression exhibit a wide range of responses to antidepressants. Unfortunately, most clinical trials fail to differentiate the effects of treatments on the primary symptoms of major depression, partially because they rely on fixed outcome measures such as total symptom severity scores or remission rates.
Methods
We performed a comprehensive analysis of the STAR*D trial with the Supervised Varimax (SV) algorithm incorporating post-model selection inference in order tolearnoutcome measures that differentiate between antidepressants. We also ran the algorithm on an independent clinical trial called CO-MED.
Outcomes
We differentiated bupropion and mirtazapine from multiple other antidepressants in STAR*D with replication in every relevant trial level. We further differentiated bupropion augmentation from mirtazapine augmentation in CO-MED. In particular, bupropion monotherapy had a greater therapeutic effect on hypersomnia than venlafaxine monotherapy in Levels 2 and 2A of STAR*D (n= 686, difference = 0.384,pFWER= 0.007). Bupropion augmentation outperformed buspirone augmentation in Level 2, especially in patients with increased weight, increased appetite and fatigue (n= 520, difference = −0.322,pFWER= 0.005). In contrast, mirtazapine monotherapy had greater therapeutic effects on insomnia, decreased weight and decreased appetite than nortriptyline monotherapy in Level 3 (n= 214, difference = 0.401,pFWER= 0.022). Similarly, venlafaxine with mirtazapine augmentation out-performed tranylcypromine in Level 4, especially in patients with insomnia, decreased weight and decreased appetite (n= 102, difference = −0.722,pFWER= 0.004). Finally, escitalopram with bupropion had larger therapeutic effects on increased weight, increased appetite and fatigue in CO-MED, while venlafaxine with mirtazapine had larger therapeutic effects on decreased weight, decreased appetite and insomnia (n= 640, difference = −0.302,pFWER= 0.022).
Interpretation
Bupropion monotherapy and augmentation are effective specifically when a patient suffers from hypersomnia, increased weight, increased appetite or fatigue. Mirtazapine monotherapy and augmentation are effective in the opposite scenario, when a patient suffers from insomnia, decreased weight or decreased appetite.
Related articles
Related articles are currently not available for this article.