REVIEW OF: Pinzi M et al, Int J Mol Sci 2025;26(24):11767
STUDY TYPE: Systematic review

We may hesitate to use bupropion for depressed patients with prominent anxiety, due to a concern that it will make them more jittery. This systematic review investigated the evidence for that caution.

The authors identified 6 studies (about 3,700 adults with major depressive disorder and clinically significant anxiety). Two were large pooled analyses of randomized trials comparing bupropion with SSRIs or placebo (6–12 weeks), 2 were smaller RCTs, and 2 were open-label trials. Anxiety was usually a secondary outcome, measured with HAM-A or anxiety subscales.

Across studies, bupropion improved anxiety scores along with depressive symptoms. In a pooled analysis of 10 RCTs (n=2,122), SSRIs had a modest edge in highly anxious patients: Response rates were about 65% with SSRIs versus 59% with bupropion, and HAM-A scores dropped slightly more with SSRIs (about 10 vs 9 points). In patients without high baseline anxiety, outcomes were similar.

Importantly, none of the trials showed a clear signal that bupropion worsened anxiety. Sexual dysfunction was less common with bupropion, while insomnia was more frequent but usually manageable. Discontinuation rates were similar to SSRIs.

CARLAT TAKE
If your patient has high baseline anxiety, SSRIs have a small advantage over bupropion. However, for patients who struggle with energy, concentration, sexual side effects, or smoking, bupropion could still be a superior choice.