Combining two drugs with different mechanisms cuts alcohol craving faster than either alone
STUDY: Naqvi A et al, Clinical Psychopharmacology and Neuroscience 2026;24(2):379–388
STUDY TYPE: Randomized, open-label trial
FUNDING: Independent
Background
Naltrexone is FDA-approved for alcohol use disorder and works by blocking opioid receptors, blunting alcohol’s rewarding effects. Baclofen, a GABA-B agonist used off-label, is approved in France and reduces alcohol craving by suppressing dopamine release.
Animal studies suggested the combination might outperform monotherapy, and this trial is the first to test that in humans.
The Study
- 97 men with alcohol dependence, sober after acute withdrawal, in India
- Randomized to naltrexone 50 mg/day, baclofen 40–60 mg/day, or the combination for 8-weeks (no placebo)
All groups improved on most measures. The graphs below show the two ratings where the combo stood out:
Obsessive Compulsive Drinking Scale (OCDS) scores at week 8 (OCDS scores fell to 2.8 versus 6.9 with naltrexone and 8.0 with baclofen alone, p = 0.025 compared to naltrexone alone but not significantly different from baclofen alone).
- Visual analogue scale (VAS) for craving (significant at earlier weeks but not at week 8); the paper implies this was the primary outcome (“our primary aim…”):
The other ratings were similar for the three groups: Relapses, heavy drinking rates, quality of life, well-being. VAS, WHOQoL BREF, and WHO-5 showed non-significant trends favoring the combo.
Side effects were mostly mild: fatigue, nausea, and headache. The combination group had more headaches (26%) and fatigue (34%) than the baclofen group, though comparable to naltrexone alone. Only one participant dropped out due to side effects, in the naltrexone group.
Limitations: open-label (no blinding), small, short, enrolled only men, and was conducted at a single center in India. The craving advantage narrowed over time, possibly because craving naturally declines with abstinence regardless of treatment.
Practice Implications
- The findings are mixed, suggesting naltrexone-baclofen has a modest benefit on cravings that fades after a month or two, likely because sobriety itself reduces craving over time. That makes sense, as baclofen’s main benefit is in cravings.
- Baclofen has safety risks if used while drinking (intoxication, sedation, dizziness, falls, muscle spasms, rare seizures), but some trials enrolled patients who were still drinking. Dosing = 10mg 1/2 po tid for 3-7 days then 1 po tid, max 60mg/day.
- For a combo pill with more robust results in alcohol use disorder, check this update on prazosin-cyproheptadine.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
