Semaglutide missed its primary endpoint in alcohol use disorder and cut heavy drinking days anyway

The edition in brief

A phase 2 double-blind trial randomised 50 treatment-seeking adults with moderate to severe alcohol use disorder to oral semaglutide, titrated from 3 mg to 7 mg daily over eight weeks, or placebo. The primary outcome, laboratory cue-elicited craving at week 6, did not differ, nor did drinks per day. Heavy drinking days fell (b = -0.580, 95 per cent CI -1.012 to -0.148), as did drinks per drinking day, naturalistic craving, alcohol-related consequences and cannabis use days. A narrative review sets out the mechanistic and epidemiological case for low-dose lithium, around 0.3 mM against the 0.6 to 1.0 mM used in bipolar disorder, as a disease-modifying agent in mild cognitive impairment, and argues for a prospective trial rather than for prescribing. In 17,071 Danish patients with incident autism diagnoses and 20,111 with ADHD between 1994 and 2016, polygenic risk for the diagnosed condition fell with each successive year of diagnosis - about 0.06 to 0.07 standard deviations per decade - which the authors read as evidence that broadening diagnostic criteria, rather than new environmental risk, drives rising rates. Across more than 17 million posts from 7736 social media users in three datasets, people with depression were consistently more reinforced by likes, the opposite of the blunted reward learning seen in laboratory tasks. In a phase 3 trial of 480 adults with inadequately treated major depression, of whom 82.5 per cent had sexual dysfunction at baseline, adjunctive lumateperone improved sexual function scores rather than worsening them.