A 5% difference in nerve pain
STUDY: Kreutzfeldt MD et al, Eur J Pain 2026
STUDY TYPE: Randomized controlled trial (crossover)
FUNDING: Novo Nordisk Foundation
Background
Among antidepressants, tricyclics and SNRIs have the best evidence for nerve pain. They likely by strengthening the spinal cords norepinephrine-based pain brakes. Bupropion blocks reuptake of norepinephrine and dopamine, and a 2001 trial found it relieved neuropathic pain.
The Study
- 67 nondepressed adults (52 completed the study) in Denmark with chronic peripheral neuropathic pain, mostly polyneuropathy.
- Each took bupropion (mostly 300 mg/day) and placebo for 6 weeks in random order, using a cross-over design. Patients could stop a phase after 3 weeks if it wasn’t helping.
- Outcome: daily pain on a 0–10 scale.
Results
Pain fell from 6.4 to 5.5 on bupropion and 6.2 to 5.8 on placebo, a half-point advantage. The study was powered to find 1.25 points.
Six patients on bupropion and two on placebo reached 50% pain relief, a number needed to treat of 15. First-line drugs run closer to 6 to 8.
Patients’ global ratings didn’t favor bupropion: as many felt worse as felt better. Burning pain improved more on bupropion.
Side Effects
Adverse events were more common on bupropion (58% vs 33%), mainly insomnia, dry mouth, and nausea. Five patients quit because of side effects, all on bupropion. Depression scores rose slightly on bupropion, an unexpected finding for an antidepressant.
Limitations
- Only 23 patients finished 6 weeks of bupropion.
- Patients with depression were excluded.
- Some older patients got only 150 mg/day.
Practice Implications
- Bupropion may reduce pain, but the effect is probably small.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
