Treatment-emergent psychiatric adverse events in patient-reported outcomes during ketamine use for major depressive disorder: a retrospective analysis.

backgroundTreatment-resistant depression (TRD) poses a significant therapeutic challenge, with remission often unattainable. Recognition and detection of treatment-emergent adverse events (TEAEs) are essential, as these events may significantly influence the quality of treatment response. This knowledge aids in personalizing care and selecting the best treatment strategy.

methodsIn a retrospective analysis of an observational study of inpatients (n = 28) with TRD, who were administered 8 ketamine infusions as an add-on therapy, psychiatric TEAEs were assessed using the Inventory of Depressive Symptomatology Self-Report 30 (IDS SR-30) and defined as symptoms that were not present at baseline but emerged during ketamine administration. The protocol was registered at ClinicalTrials.gov on Jan 2, 2020 (NCT04226963).

resultsSleep disturbances were the most consistently reported psychiatric TEAEs, with nighttime sleep problems increasing by the 7th infusion and persisting at follow-up (n = 5), and early waking reported across timepoints (n = 3-4). Appetite and weight changes were also observed, with both increased and decreased appetite peaking early in treatment (n = 7 and n = 6 at the 3rd infusion) and persisting at lower levels at follow-up. In contrast, mood, cognitive, and most somatic symptoms were rare (≤ 2-4 participants), and suicidal ideation was minimal (n = 1 at the 3rd infusion and follow-up).

conclusionsThis study identified sleep disturbances, appetite changes, and weight fluctuations as common patient-reported TEAEs during ketamine use for TRD inpatients. These preliminary results highlight the need for larger, controlled trials to gain a comprehensive understanding of ketamine's psychiatric safety profile.