Suicidality during intranasal (es)ketamine treatment: A retrospective cohort study

Intranasal (es)ketamine has shown efficacy in therapy of treatment-resistant depression (TRD). However, its effects on suicidality have not been fully elucidated.

We conducted a retrospective longitudinal cohort study of 80 patients affected by TRD, treated with intranasal (es)ketamine. Suicidality was assessed using item 10 of the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and item 9 of the Beck-Depression-Inventory-II (BDI-II). We measured patient- and transition-level fluctuations of suicidality, tested temporal clustering using mixed-effects logistic regression, examined associations between non-suicidal depressive symptom change and suicidality worsening, and explored baseline predictors.

Mean suicidality ratings decreased modestly. Upward and downward category transitions occurred at similar frequencies across treatment (MADRS: 57 increases and 50 decreases across 767 valid transitions, 7.4% vs. 6.5%; BDI-II: 22 and 23 across 741 transitions, 3.0% vs. 3.1%). At least one upward transition occurred in 38.8% on MADRS and 21.3% on BDI-II. Transient elevations were more frequent than sustained elevations. Sustained elevation occurred at 15.0% on MADRS and 7.5% on BDI-II. Increases did not cluster by treatment phase. MADRS, but not BDI-II, upward transitions were associated with concurrent and lagged worsening in non-suicidal depressive symptoms. Higher baseline suicidality showed the most consistent association with later worsening across both measures. Two serious adverse events occurred, including one suicide.

In this routine-care cohort, suicidality decreased on average, with no evidence of treatment-phase-specific worsening. Nonetheless a minority of patients showed transient or, less often, sustained increases in suicidality, supporting necessity of continuous suicidality monitoring throughout (es)ketamine treatment.