An anti-seizure medication shows promise in reducing the likelihood of heavy drinking, desire to drink, and positive alcohol expectancies, according to new research published in Addiction. Importantly, the study found no evidence that the results varied based on the presence of a genetic variant associated with alcohol use disorder.
Topiramate is a medication that is commonly used to treat epilepsy and prevent migraine headaches. It works by regulating the activity of certain chemicals in the brain that can contribute to seizures or migraines. In recent years, topiramate has also been studied as a potential treatment for alcohol dependence, as it may help reduce cravings and symptoms of withdrawal. But scientists are not sure if a specific variation in the GRIK1 gene (rs2832407) affects how well topiramate works to reduce drinking.
“My research interests include personalizing substance use disorder treatments for people based on different characteristics, including why they use substances, co-occurring psychological disorders, and biological characteristics (e.g., genetics), among other considerations,” said study author Victoria Votaw, a PhD candidate and National Institute on Alcohol Abuse and Alcoholism predoctoral fellow at the University of New Mexico.
“Therefore, I was very interested in research showing that the effect of topiramate, a medication that has shown efficacy for treating alcohol use disorder, on alcohol use outcomes might vary by a type of genetic mutation called a single-nucleotide polymorphism. Upon doing a deeper dive into this literature, I realized the findings were mixed, and my co-authors and I decided to look at daily data reported via telephone from a trial of topiramate to further explore this research question.”
“Using daily data might help clarify how topiramate works for different people and provide more information regarding whether topiramate’s effectiveness depends on the genetic variant we examined.”
The study involved 164 people who wanted to stop or reduce their drinking. They were randomly divided into two groups: one group received topiramate, while the other group received a placebo (a “dummy” medication with no active ingredients). Participants were seen once a week for six weeks and the medication dosage was gradually increased from 25 mg/day to a maximum of 200 mg/day.
To track their progress, participants were asked to complete a daily phone survey using an interactive voice response system (IVR) over a 12-week period. This method is considered reliable and potentially more accurate than traditional methods of asking people to recall their alcohol use over a specific period of time. To make it easier for participants to complete the daily survey, they were allowed to call between 5:00 pm and 9:00 pm, which is when they were least likely to drink heavily.
During the phone survey, participants reported the number of standard drinks consumed the previous day, responded to three desire-to-drink assessments (e.g. “The idea of drinking today is appealing”), and answered two questions regarding their expectations for drinking later in the night (e.g. “Likely to make me less tense and more relaxed”).
“We found that topiramate’s effect in reducing heavy drinking did not depend on the genetic variant we examined. In fact, across all people included in the study, topiramate reduced the likelihood of drinking heavily, which is defined as a day on which women drink 4 or more drinks and men drink 5 or more drinks, by 74%,” Votaw told PsyPost.
“The main takeaway is that topiramate is helpful in reducing alcohol use and should be considered a treatment option for alcohol use disorder, but the genetic variant does not influence those effects. However, topiramate does have some side effects, like confusion and dizziness, so it is important for someone who is interested in reducing their drinking to talk with their doctor.”
The results from the study hint that topiramate might reduce drinking by modifying expectations of alcohol’s effects.
“We found that participants who received topiramate treatment had lower expectations that alcohol would make them feel less tense and more relaxed, which are called tension reduction expectancies, during the 12-week treatment period, compared to those who received placebo. In fact, topiramate reduced these expectations more than expectations that alcohol would lead to a good time,” Votaw explained.
“These findings were not expected and might tell us that topiramate could be particularly effective for those who normally drink to feel less tense and more relaxed. More research is still needed to answer this question, but this could be a promising way to help select treatments for those who drink to reduce tension.”
The study, “An intensive longitudinal examination of topiramate treatment for alcohol use disorder: a secondary analysis of data from a randomized controlled trial“, was authored by Victoria R. Votaw, Katie Witkiewitz, M. Lee Van Horn, Richard C. Crist, Timothy Pond, and Henry R. Kranzler.