Vagus nerve stimulation misses its primary endpoint and still looks useful

The edition in brief

RECOVER randomised 493 adults with markedly treatment-resistant depression - a mean of 13.3 lifetime antidepressant trials and a current episode of 17.8 years - to active or sham adjunctive vagus nerve stimulation for 12 months, triple-blind. The prespecified primary outcome, percent time in MADRS response, did not separate the groups. Clinician-rated symptoms (39.6% vs 30.7%), global improvement (53.8% vs 39.8%), work function and quality of life all favoured active stimulation, as did a combined metric. Over 80% of those who benefited at 12 months still had that benefit at 24 months, and about 30% of non-responders at 12 months improved in the second year. A separate assessor-blind trial randomised 136 adults with treatment-resistant schizophrenia and persistent auditory hallucinations to nine sessions of virtual reality-assisted therapy or nine of targeted CBT; the time-by-treatment interaction favoured virtual reality (P = 0.013, Cohen d = 0.614 at 3 months), though both arms improved. A propensity-matched study of 1,062,722 pairs found hospitalisation with infection of any body system associated with more psychiatric and neurologic diagnoses over two years, with cognitive deficits the largest absolute excess and infectious encephalitis the largest relative one. On the regulatory side, the FDA cleared a supplement to Alembic's abbreviated application for generic sublingual asenapine - a supply matter, not a new indication. And in England, all-cause mortality after COVID infection in people with severe mental illness stayed about 55% higher than in those without, through and after vaccine roll-out, with full vaccination ending lower in this group.