Biobehavioral mechanisms of topiramate's effects on alcohol use: an investigation pairing laboratory and ecological momentary assessments

Abstract

Topiramate reduces drinking, but little is known about the mechanisms that precipitate this effect. This double-blind randomized placebo-controlled study assessed the putative mechanisms by which topiramate reduces alcohol use among 96 adult nontreatment-seeking heavy drinkers in a laboratory-based alcohol cue reactivity assessment and in the natural environment using ecological momentary assessment methods. Topiramate reduced the quantity of alcohol heavy drinkers consumed on drinking days and reduced craving while participants were drinking but did not affect craving outside of drinking episodes in either the laboratory or in the natural environment. Topiramate did not alter the stimulant or sedative effects of alcohol ingestion during the ascending limb of the blood alcohol curve. A direct test of putative mechanisms of action using multilevel structural equation mediation models showed that topiramate reduced drinking indirectly by blunting alcohol-induced craving. These findings provide the first real-time prospective evidence that topiramate reduces drinking by reducing alcohol’s priming effects on craving and highlight the importance of craving as an important treatment target of pharmacotherapy for alcoholism.

Active Ingredients of Treatment and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later

“…Experience sampling through ecological momentary assessment ( EMA ; Shiffman, 2009) may provide a better method for measuring change by assessing them often, in real time, and in individuals’ daily lives. For instance, EMA was utilized by Litt and colleagues (2009b) to support coping skills as a mediator of CBT’s effect on reducing chronic pain, and has demonstrated some utility for elucidating mechanisms of pharmacotherapies for alcohol use through frequent measurement of craving (see Miranda et al, 2014). We recognize, however, that EMA still contains many of the limitations of reliability and validity associated with traditional self-report assessment.…”

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.…”

Pharmacological treatment options for alcohol use disorder

“…A systematic review of seven randomized controlled studies showed that topiramate has the greatest effect on abstinence, observing a reduction in heavy drinking, while no effect on craving was found (87). A double-blind placebo-controlled study showed that topiramate reduced the amount of alcohol consumed by heavy drinkers on drinking days and the craving during the drinking period but was not effective regarding craving outside drinking periods (88). However, there are also studies that have not found topiramate to be effective in AUD (89).…”