Alcohol-medication interactions: A systematic review and meta-analysis of placebo-controlled trials

•Alcohol consumption may interact and limit therapeutic effects of some medications.•Other xenobiotics in alcoholic beverages may interact with medications.•Other xenobiotics may influence alcohol-medication interactions (AMI).•For certain medications, AMI persist after the exclusion of other xenobiotics.•Patients who use these medications should avoid alcohol consumption. Alcohol and other xenobiotics may limit the therapeutic effects of medications. We aimed at investigating alcohol-medication interactions (AMI) after the exclusion of confounding effects related to other xenobiotics. We performed a systematic review and meta-analysis of controlled studies comparing the effects induced by alcohol versus placebo on pharmacodynamic and/or pharmacokinetic parameters of approved medications. Certainty in the evidence of AMI was assessed when at least 3 independent studies and at least 200 participants were available. We included 107 articles (3097 participants): for diazepam, cannabis, opioids, and methylphenidate, we found significant AMI and enough data to assign the certainty of evidence. Alcohol consumption significantly increases the peak plasma concentration of diazepam (low certainty; almost 290 participants), cannabis (high certainty; almost 650 participants), opioids (low certainty; 560 participants), and methylphenidate (moderate certainty; 290 participants). For most medications, we found some AMI but not enough data to assign them the certainty grades; for some medications, we found no differences between alcohol and placebo in any outcomes evaluated. Our results add further evidence for interactions between alcohol and certain medications after the exclusion of confounding effects related to other xenobiotics. Physicians should advise patients who use these specific medications to avoid alcohol consumption. Further studies with appropriate control groups, enough female participants to investigate sex differences, and elderly population are needed to expand our knowledge in this field. Short phrases suitable for indexing terms •Among participants taking diazepam, those who consumed alcohol achieved higher peak plasma concentration (low certainty; almost 290 participants) and area under the curve (very low certainty; 270 participants) of this medication compared to those who consumed placebo•Among participants taking cannabis, those who consumed alcohol achieved higher peak plasma concentration (high certainty; almost 650 participants), in a shorte