In a small group of 11 patients with treatment-resistant depression who initially responded to an acute course of ketamine infusions, ongoing maintenance infusions helped sustain the antidepressant effect for some. All patients had lower depression scores during maintenance treatment than at baseline. At the end of the observation period, 4 patients continued maintenance ketamine, 1 switched to intranasal ketamine, 4 stopped because the drug lost its effect, 1 stopped due to side effects, and for 2 the reason was unrecorded. No major adverse events occurred, and the treatment was generally well tolerated. The authors suggest maintenance ketamine may help some responders, but more research is needed on optimal duration and long-term safety.
A letter to the editor raises concerns about using nitrous oxide (N2O) for treatment-resistant major depressive disorder (trMDD). The authors note that cobalamin dysregulation and folate deficiency are already documented in trMDD, citing evidence that cerebrospinal fluid metabolite abnormalities appear in over half of such patients, with cerebral folate deficiency most common, and that vitamin B12 levels predict deep white matter hyperintensities in MDD. They argue that N2O could worsen these effects, especially since its antidepressant effects are transitory, and call for clarifying why one-carbon metabolism dysregulation exists before considering N2O as a treatment.