A seizure med in alcohol use disorder gets its first analysis
STUDY: Obitulata V et al, J Clin Psychopharmacol 2026
STUDY TYPE: Systematic review and meta-analysis of randomized controlled trials
FUNDING: Independent
Background
Zonisamide, an anticonvulsant that raises GABA and dampens glutamate, has scattered studies in alcohol use disorder, and this is the first analysis to pool them.
The Study
- 344 adults with alcohol use disorder in 5 randomized, placebo-controlled trials run in the United States from 2010 to 2024.
- Zonisamide (400 to 500 mg/day) versus placebo, both paired with brief counseling or psychotherapy, for 12 to 16 weeks.
- Outcomes: drinks per day, drinking days, and heavy drinking days.
Results
- Zonisamide lowers drinks per day (mean difference -0.79 drinks; 95% CI -0.95 to -0.63) and drinking days by about 8 days over 12 weeks, ie around 3 days/month (mean difference -7.93 days; 95% CI -11.03 to -4.83) versus placebo.
- Heavy drinking days didn’t improve (mean difference -0.95; 95% CI -2.12 to 0.22), a result confirmed in sensitivity analysis.
- Anxiety and irritability were about half as common on zonisamide vs placebo (RR=0.53; P=0.007).
- In other populations, zonisamide improved binge eating and weight loss.
Side Effects
Word-finding and memory problems showed up in these trials. Other trials point to fatigue, concentration problems, dyscoordination, dizzy.
Serious but rare risks include decreased sweating (hyperthermia, especially in children), severe Stevens Johnson rash, and motor vehicle accidents (coordination). Avoid in renal failure (eGFR < 50 mL/min).
Limitations
Evidence is limited: 5 trials, 344 patients, only 12 to 16 weeks of treatment. The heavy drinking days result hinged on one study, and all trials relied on self-reported drinking.
Practice Implications
- These are mild benefits, with no change in heavy drinking days, one of the most important health risks.
- Zonisamide is third line for alcohol use disorder. Start at 100 mg/day and titrate to 400 mg/day, raising by 100 mg every 1-2 weeks for 8 weeks based on response, max 500 mg/day.
- Consider for patients with comorbidities that may respond to zonisamide: Epilepsy, obesity, binge-eating, Parkinson’s disease, and possibly migraines.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
