The drug topiramate (Topamax) is effective at helping alcohol-dependent individuals and heavy drinkers avoid heavy drinking, but many patients and clinicians have shied away from using the drug due to its reputation for side effects, such as drowsiness and cognitive difficulties. A new risk-benefit analysis from psychiatrists in the Perelman School of Medicine at the University of Pennsylvania, shows that topiramate is both highly effective and seems to cause fewer side effects in drinkers who carry a specific genotype for the gene GRIK1. The findings appear this week in the Journal of Clinical Psychiatry.

GRIK1 encodes a certain neurotransmitter receptor subunit on brain cells, known as kainate receptors. A team led by Penn’s Henry R. Kranzler, MD, a professor of Psychiatry and director of the Center for Studies of Addiction, were the first, in 2009, to show that that people with a C variant in the DNA sequence in the GRIK1 genewere significantly more likely to be alcohol dependent.

Then, in a landmark 2014 trial, Kranzler and colleagues found evidence that topiramate’s effectiveness was largely limited to a subset of people who had two copies of the C allele in that location inGRIK1 (one copy inherited from each parent).

“In our new study, we’ve gone a step further with that data and mapped the incidence of side effects in those with the C variant and those without,” Kranzler said, noting that complaints from patients’ about sleepiness and memory difficulties, especially early in treatment, have been common among those taking the drug.

The team, including lead author Richard Feinn, PhD, an assistant professor of medical sciences at Quinnipiac University; and Brenda Curtis, PhD, a research associate in the department of Psychiatry at Penn Medicine, started with an effectiveness measure known as Number Needed to Treat (NNT), which indicates how many patients need to be treated, on average, for one patient to have a successful outcome that would not occur with placebo treatment. The NNT for topiramate turned out to be 5.29 for their full sample of 138 patients. For comparison, the published NNT figures for other standard alcoholism treatment drugs, such as naltrexone and acamprosate, are about nine. Adjusting the topiramate NNT for adverse events such as numbness/tingling in the extremities, change in taste, loss of appetite and weight, and difficulty concentrating, and with memory, that figure rose to about 7.5. This means that about eight patients would need to be treated with topiramate to produce a successful outcome without causing any additional moderate or worse adverse events during the entire 12-week treatment period.