Epilepsy drug topiramate shows mixed results for treating combined alcohol and tobacco use

An 18-week experimental study examining the effects of topiramate on tobacco smoking and alcohol use found no differences between groups treated with topiramate and those receiving placebo treatment in the last 4 weeks of treatment. However, the authors report a lower average percentage of heavy drinking days and drinks per day in participants treated with the highest tested dose of the substance compared to the other groups across the assessments conducted after the target quit date. The research was published in Alcohol Clinical & Experimental Research.

Topiramate is a prescription medication originally developed as an antiepileptic drug to treat seizures. It is also commonly used for migraine prevention and, in combination with other drugs, for weight management.

Topiramate works by modulating multiple neurotransmitter systems, including enhancing the activity of the inhibitory neurotransmitter GABA and reducing the excitatory activity of the neurotransmitter glutamate. Because of these mechanisms, topiramate can reduce the heightened excitability of neurons in the brain.

The medication is sometimes used off-label for conditions such as bipolar disorder, alcohol use disorder, and binge eating disorder. However, it has substantial cognitive and neurological side effects (e.g., cognitive slowing, difficulty with word finding, tingling sensations in hands or feet), which limit its long-term use.

Study author Jason D. Robinson and his colleagues wanted to explore whether topiramate would be effective in treating individuals with alcohol use disorder and tobacco use disorder. More specifically, they wanted to see whether 250 mg and 125 mg of topiramate per day would result in reducing heavy drinking and cigarette smoking behaviors in individuals motivated to try to quit both substances. The study authors hypothesized that the higher dose would be more effective than the lower dose.

Study participants were 236 adults who met the criteria for both alcohol use disorder and tobacco use disorder. They were recruited from San Diego, Houston, and Charlottesville. Participating women had been drinking at least 8 standard drink units (of alcohol) per week in the past 30 days, while this minimum limit was 15 standard drink units for men.

One standard drink unit is the amount of alcohol that contains about 14 grams of pure ethanol, roughly equivalent to a small beer (350 ml), a glass of wine (150 ml), or a shot of spirits (45 ml). They were also smoking an average of 5 or more cigarettes per day in the 30 days before the study.

Study participants were randomly divided into three groups. One group was assigned to receive a high dose of topiramate, up to 250 mg/day; the second group would receive up to 125 mg/day of topiramate; and the third group would receive a placebo.

The placebo consisted of pills that looked like topiramate pills but contained no active ingredients. Participants did not know which treatment they were receiving, and the same was the case for the researchers directly working with them. In other words, the study was double-blind.

The treatment lasted for 18 weeks. During this period, participants took their assigned treatment and received adherence counseling, including a self-help manual for smoking cessation. In the first 5 weeks, the dose was gradually increased, and at the start of week 6, participants were expected to actively stop both alcohol drinking and tobacco smoking.

Results showed no differences between the study groups regarding the primary outcomes. In other words, the three groups did not differ significantly in the percentage of heavy drinking days and the rate of continuous smoking abstinence in the last 4 weeks of treatment.

However, study authors report that participants in the group that received 250 mg of topiramate had a lower average percentage of heavy drinking days and drinks per day compared to the other two groups when all assessments done from week 6 onward were taken into account. Similarly, participants in both topiramate groups smoked fewer cigarettes per day and reported greater cigarette abstinence than those in the placebo group during the same period.

“While the primary analyses did not find evidence that topiramate decreases drinking and smoking behavior, likely influenced by a high attrition rate and poor medication adherence, exploratory repeated measures analyses suggest that topiramate 250 mg reduces drinking behavior and that both the 125 mg and 250 mg doses reduce smoking behavior,” the study authors concluded.

The study contributes to the scientific understanding of the effects of topiramate. However, it should be noted that 236 participants started the treatments, but only 107 completed them, which is less than half. This extremely high attrition rate could have substantially altered the results.

The paper, “High- and low-dose topiramate for the treatment of persons with alcohol use disorder who smoke cigarettes: A randomized control trial,” was authored by Jason D. Robinson, Robert M. Anthenelli, Paul M. Cinciripini, Maher Karam-Hage, Yong Cui, George Kypriotakis, and Nassima Ait-Daoud Tiouririne.