Ketamine worked in treatment-resistant bipolar depression without tipping anyone into mania

The edition in brief

Ket-BD randomised 68 adult outpatients with treatment-resistant bipolar I or II depression, all on a stable mood stabiliser or antipsychotic and having failed at least two adequate trials, to four flexibly dosed infusions of ketamine or midazolam over two weeks. At day 14 the ketamine group's MADRS score was 7.3 points lower (95% CI -12.0 to -2.5, Cohen's d 0.7). The safety result matters as much as the efficacy one: no mania, hypomania, psychosis or suicide attempt occurred in either arm, with one case of subthreshold mixed features in each. Blinding was imperfect, with 47% correctly guessing allocation after the first infusion. A network meta-analysis of 95 randomised trials and 39 interventions in 5,898 antipsychotic-treated patients with schizophrenia spectrum disorders ranked pharmacological options for weight gain. Semaglutide gave the largest reduction at 10.98 kg (95% CI -13.33 to -8.62), followed by liraglutide at 5.43 kg, topiramate at 3.95 kg, metformin at 3.86 kg and exenatide at 2.97 kg, all at moderate certainty. Only semaglutide and metformin achieved clinically meaningful weight change of 5% or more. A pragmatic SMART trial in 316 youths with anxiety found fluoxetine and CBT equivalent as initial treatment, and combination therapy no better than continuing monotherapy in those who had not remitted at 12 weeks. Home-based tDCS for depression produced a small effect that did not survive removal of the single largest positive trial.