Explaining increased efficacy of naltrexone in the treatment of alcohol dependent patients with a family history of alcohol use disorder: A systematic review on the role of reward sensitivity and sweet liking

A positive family history of alcohol use disorder (FHA+) is one of the strongest risk factors for developing alcohol use disorder (AUD) compared. Importantly, naltrexone (NTX) has shown higher efficacy in treating FHA+ AUD patients than FHA- AUD patients. Possibly, this may be explained by the attenuation of high reward sensitivity and liking sweet substances ("sweet liking"; SL) in FHA+ AUD patients. This systematic review explores whether attenuation by NTX of reward sensitivity and SL explains its higher efficacy in FHA+ compared to FHA- AUD patients. Separate systematic literature searches were performed on the effect of NTX in FHA+ AUD patients, the effect of NTX on reward sensitivity, and the associations of FHA+ with reward sensitivity and SL. In total, 36 eligible studies were included (6 for the effect of NTX in FHA+ AUD patients, 18 for reward sensitivity, and 12 for sweet liking). In 5 out of 6 studies, a moderating effect of FHA+ on NTX treatment efficacy in AUD was shown, with higher efficacy of NTX in FHA+ AUD patients. In 6 out of 8 studies, reward sensitivity moderated the treatment effect of NTX in AUD, and in 9 of 10 studies, reward sensitivity was attenuated by NTX. In 3 studies, SL positively moderated the effect of NTX in AUD. Finally, in 9 of 9 studies, SL was attenuated by NTX and enhanced by (partial) opioid agonists. Increased reward sensitivity (and sweet-liking as its possible indicator) appeared to be positively associated with FHA+ and was attenuated by NTX, which may (partly) explain the increased effect of NTX in FHA+ AUD patients. These results may foster personalized pharmacotherapy in AUD patients.