Semaglutide misses its primary outcome in alcohol use disorder and still looks interesting

The edition in brief

The psychiatry desk opens with a phase 2 trial of oral semaglutide in 50 treatment-seeking adults with moderate to severe alcohol use disorder. The primary outcome, laboratory cue-elicited craving, was not reduced, but heavy drinking days, drinks per drinking day, naturalistic craving, alcohol-related consequences and cannabis use days all fell. A pattern of secondary benefits with a negative primary endpoint is a signal to watch, not a reason to prescribe. A major evidence review argues that dopaminergic hyperactivity is not a universal final common pathway in the schizophrenia spectrum: about a third of patients with treatment resistance show no rise in striatal dopamine synthesis capacity, and the efficacy of the muscarinic agonist xanomeline-trospium, which has no direct D2 antagonism, is offered as proof that non-dopaminergic routes can reduce psychosis. A Danish case-cohort of 17,071 people with autism and 20,111 with attention-deficit/hyperactivity disorder found polygenic scores falling with each year of diagnosis, about 0.06 to 0.07 standard deviations per decade, which fits broadening diagnostic criteria rather than new environmental risk. An updated meta-analysis of 24 studies found no baseline inflammatory marker separated antidepressant responders from non-responders overall, with only nominal signals for interleukin-2 and interleukin-6 in recent studies. A clinic pearl covers telling akathisia from agitation. The edition closes with a double-blind sham-controlled trial of a circadian rhythm stabilisation app in 93 adults with mood disorders: recurrence was far higher on the sham app, incidence rate ratio 3.39 (95% CI 1.86 to 6.17).