Which Antidepressant Does Not Cause Emotional Blunting?
Bupropion is the antidepressant least likely to cause emotional blunting, as it does not significantly decrease emotional responsiveness compared to SSRIs and SNRIs. 1, 2
Evidence for Bupropion's Advantage
Bupropion appeared less frequently associated with emotional blunting in a large survey of 669 depressed patients on treatment, where the overall rate of emotional blunting was 46% across all antidepressants, but bupropion showed lower rates 2
In three randomized controlled trials comparing bupropion to SSRIs (escitalopram) and SNRIs (venlafaxine), only a minority of participants (≤6%) experienced more emotional blunting post-treatment, with no significant differences between treatment groups 1
Bupropion is the only antidepressant on the U.S. market with no appreciable activity on serotonin concentrations in the central nervous system, instead working through dopamine-norepinephrine reuptake inhibition, which mechanistically explains its lower propensity for emotional blunting 3, 4, 5
Why SSRIs and SNRIs Cause More Emotional Blunting
Emotional blunting is theorized to be an adverse effect particularly associated with serotonin reuptake inhibitors, though it may also represent a residual depressive symptom in some cases 1
Among depressed patients on monoaminergic antidepressants (SSRIs, SNRIs), emotional blunting appears common to all of these agents, with 46% of treated patients reporting this side effect 2
The American College of Physicians notes that sexual dysfunction (a related serotonergic side effect) occurs with a weighted average incidence of 40% across SSRIs, and bupropion had significantly lower rates of sexual adverse events than fluoxetine or sertraline 6, 7
Clinical Implications
Bupropion is as efficacious as SSRIs and SNRIs for treating major depressive disorder, with the added advantage of less somnolence and sexual dysfunction 4, 5
Bupropion has comparable efficacy to escitalopram in two placebo-controlled trials and similar efficacy to venlafaxine XR in two of three trials 5
The main caveat with bupropion is a dose-dependent risk of seizures, requiring gradual titration to a maximum dose of 450 mg/day for immediate-release and 400 mg/day for sustained-release formulations 7, 3
Important Caveats
Emotional blunting cannot be described simply as a side effect of antidepressants but also as a symptom of depression itself, as higher emotional blunting scores correlate with higher depression severity scores (r = 0.521) 2
Even patients with low depression scores (HAD-D ≤7) on antidepressants had higher emotional blunting scores than recovered controls, suggesting a true medication effect beyond residual depression 2
Among patients experiencing emotional blunting, 37% had a negative perception and 38% positive, with men reporting more negative perceptions than women 2