Bupropion’s reputation for worsening anxiety didn’t show up when it was added to an SSRI
STUDY: Jo SH et al, Clin Psychopharmacol Neurosci 2026
STUDY TYPE: Randomized controlled trial (open-label, post hoc subgroup)
FUNDING: Otsuka Pharmaceutical (maker of aripiprazole)
Background
Depression with prominent anxiety responds less well to SSRIs, and many clinicians hesitate to add an activating drug like bupropion. No trial had compared the two most common add-ons in this group.
The Study
- 48 Korean adults with anxious depression who hadn’t responded to at least 4 weeks of an SSRI at full dose.
- Randomized to add aripiprazole (2.5 to 10 mg) or bupropion (150 to 300 mg) for 6 weeks; 28 and 20 patients.
- Primary outcomes: Depression scale (HAM-D) and its anxiety/somatization factor.
Results
Depression scores fell about 12 points in both groups, and anxiety scores fell similarly.
Remission favored aripiprazole, 57% versus 35%, but the study had only a one-in-three chance of detecting a gap that size, and the difference wasn’t significant. That said, this could be a real difference as bupropion did fail in its only large, placebo controlled augmentation trial of depression.
Aripiprazole reduced fatigue and somatic aches more, while bupropion improved libido more.
Side Effects
- No one dropped out due to side effects.
- Aripiprazole: more movement effects, including tremor (18%), akathisia (14%), and dystonia (11%).
- Bupropion: more autonomic effects, such as nausea, dry mouth, constipation, and palpitations.
Limitations
- Small and open-label, so clinicians knew which drug patients received.
- A post hoc subgroup of a larger trial.
- Funded by the maker of aripiprazole.
- Only 6 weeks, and benzodiazepines were allowed.
Practice Implications
This small study doesn’t settle which add-on works better, but anxiety alone shouldn’t steer you away from bupropion. Larger studies back that point.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
