REVIEW OF: Morley KC et al, Am J Psychiatry 2024;181(5):403–411
STUDY TYPE: Randomized double-blind placebo-controlled trial

Topiramate’s GABA-boosting and dopamine-regulating qualities make it a good choice for alcohol use disorder (AUD), even without FDA approval. In fact, in the VA system, topiramate is prescribed more than acamprosate, injectable naltrexone, and disulfiram combined. There is good evidence to support its use, and in this study it went head-to-head against oral naltrexone, the AUD mainstay. This study also sought to explore whether certain genetic polymorphisms (rs2832407 in GRIK1 for topiramate and rs1799971 in OPRM1 for naltrexone) affect treatment outcomes. 

This 12-week double-blind RCT stratified 147 patients with AUD by genotype. They were then randomly assigned to either topiramate (starting at 25 mg and titrated up to a max of 100 mg twice daily) or naltrexone (50 mg once daily, given with a second placebo pill to match topiramate’s twice-daily dosing). The primary outcome was the number of heavy drinking days per week, while secondary outcomes included standard drinks per day, body mass index (BMI), alcohol craving, liver function markers, mood, and side effects.

Participants in both groups significantly reduced heavy drinking days per week, with no difference between the two groups. Topiramate significantly outperformed naltrexone in reducing the average number of drinks per drinking day, BMI, alcohol craving, and levels of gamma-glutamyltransferase (GGT, a liver enzyme marker of heavy drinking). No differences were seen between the two drugs in mood-related outcomes, such as anxiety and depression. Both medications were generally well tolerated, although patients taking topiramate reported more side effects like attention problems, paresthesia, and appetite loss. Contrary to the researchers’ hypothesis, neither of the genetic polymorphisms (rs2832407 or rs1799971) moderated the response to topiramate or naltrexone.

CARLAT TAKE
Topiramate seems to be at least as effective as naltrexone for reducing alcohol consumption. When treating patients with AUD, we recommend using topiramate for patients with comorbid epilepsy, binge eating, obesity, or migraines. Stick to naltrexone for patients with glaucoma, cognitive complaints, or a history of kidney stones.