AIMS
To compare quantitatively the efficacy and tolerability of pharmacologically active interventions in the treatment and prevention of alcohol-induced hangover.

METHODS
Systematic review of placebo-controlled randomised trials in healthy adults that evaluated any pharmacologically active intervention in the treatment or prevention of hangover. We searched Medline, Embase, PsycINFO and CENTRAL from database inception until 1 August 2021. The primary efficacy outcome was any continuous measure of overall hangover symptoms and the primary tolerability outcome the number of people dropping out due to adverse events (AEs). Quality was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework.

RESULTS
21 studies were included reporting on 386 participants. No two studies reported on the same intervention; as such, meta-analysis could not be undertaken. Methodological concerns and imprecision resulted in all studied efficacy outcomes being rated as very low quality. When compared with placebo, individual studies reported a statistically significant reduction in the mean percentage overall hangover symptom score for clove extract (42.5% vs. 19.0%, p<0.001), tolfenamic acid (84.0% vs. 50.0%, p<0.001), pyritinol (34.1% vs. 16.2%, p<0.01), Hovenia dulcis fruit extract (p=0.029), L-cysteine (p=0.043), red ginseng (21.1% vs. 14.0%, p<0.05) and Korean pear juice (41.5% vs 33.3%, p<0.05). All studied tolerability outcomes were of low or very low quality with no studies reporting any drop-outs due to AEs.

CONCLUSIONS
Only very low quality evidence of efficacy is available to recommend any pharmacologically active intervention for the treatment or prevention of alcohol-induced hangover. Of the limited interventions studied, all had favourable tolerability profiles and very low quality evidence suggests clove extract, tolfenamic acid, and pyritinol may most warrant further study.