Topiramate Treatment of Alcohol Use Disorder in Veterans with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Trial

Abstract

Background The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these co-morbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders. Methods This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300mg/day in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity. Results Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared to placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment. Conclusions These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity – particularly hyperarousal symptoms.. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated.

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

“…Neurobiologically, topiramate acts by facilitation of GABAergic neurotransmission and/or inhibition of glutamatergic signaling in corticomesolimbic pathways. Some studies suggest that topiramate may decrease craving for alcohol, which may contribute to its effects on drinking in humans [81, 103–105]. Topiramate was found to have no effect on cue-induced reactivity in an laboratory challenge paradigm in 61 heavy drinkers pre-treated with topiramate or placebo; instead, it altered the subjective experience of intoxication [105].…”

Concurrent Treatment of Substance Use and PTSD

“…Only recently has topiramate been examined to target co-occurring alcohol use disorder and PTSD [96–98]. Batki explored the use of topiramate versus placebo in a 12-week randomized control trial in veterans with co-occurring alcohol use disorder and PTSD [99]. Veterans in the topiramate group had fewer standard drinks per week and drinks per drinking day compared to the placebo group, although these reductions were not statistically significant.…”

The Corticotropin Releasing Factor Receptor 1 in Alcohol Use Disorder: Still a Valid Drug Target?

“…It failed to suppress craving in one human laboratory study (Miranda et al, 2008), though in a recent study by the same group, it reduced craving only while participants were drinking, suggesting that it reduces drinking by blunting alcohol-induced craving (Miranda et al., 2016). However, a recent DBPC trial of topiramate in 30 veterans with comorbid PTSD and AUD found it to be effective in reducing alcohol craving and drinking and in reducing PTSD symptom severity (Batki et al, 2014), suggesting that it can suppress stress-related drinking.…”