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A meta-regression of methodological features predicting the effects of pharmacotherapies on subjective response to alcohol.

BACKGROUND
Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. This study consists of a meta-regression testing whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predicts the efficacy of AUD pharmacotherapies on subjective responses to alcohol.


METHODS
Medication effects on alcohol-induced stimulation, sedation, negative mood, and craving during the alcohol administration were computed (k=49 studies, 24 medications).


RESULTS
Meta-regression analyses indicated a significant and positive effect of drinks per month on alcohol-induced stimulation (β=.142, p<.0001), such that as drinking increases, the benefit of medication over placebo weakens. There was an effect of drinks per month on negative mood (β=-.164, p=.0248), such that at high levels of drinks per month, the effects of medications on negative mood are stronger. For sedation, there was an effect of peak BrAC (β=.119, p=.0002), such that at low levels of peak BrAC, the effects of medication on sedation are null. For craving, there was a peak BrAC × Drinks per Month interaction such that at low levels of BrAC, a heavier drinking sample is required to detect medications anti-craving effects. Sensitivity analyses comparing naltrexone studies and non-naltrexone studies suggested that naltrexone was less sensitive to drinks per month across subjective response domains.


CONCLUSIONS
These analyses suggest that design features are critical in studies testing the effects of pharmacotherapies on subjective responses to alcohol. By specifying the significance and directionality of these effects, as well as the specific points in BrAC or drinks per month at which medication effects are detectable, this study offers recommendations for alcohol administration studies for AUD medications development purposes.