Replication of distinct trajectories of antidepressant response to intravenous ketamine

Background: The goal of this study was to replicate previous findings of three distinct treatment response pathways associated with repeated intravenous (IV) ketamine infusions among patients with major depressive disorder (MDD).Methods: We conducted growth mixture modelling to estimate latent classes of change in depression (Quick Inventory of Depressive Symptomatology-Self Report, QIDS-SR) across six treatment visits in 298 patients with MDD treated with IV ketamine in an outpatient community clinic. Mean age was 40.36 and patients were primarily male (58.4 %). The sample had relatively severe depression (QIDS-SR = 16.61) at pre-treatment and the majority had not responded to at least two prior medications.Results: Best-fit indices indicated three trajectory groups to optimally demonstrate non-linear, quadratic changes in depressive symptoms during ketamine treatment. Two groups had severe depression at baseline but diverged into a group of modest improvement over the treatment course (n = 78) and a group of patients with rapid improvement (n = 103). A third group had moderate depression at baseline with moderate improvement during the treatment course (n = 117). Additional planned trajectory comparisons showed that suicidality at entry was higher in the high depression groups and that change in suicidality severity followed that of depression.Limitations: This was a retrospective analysis of a naturalistic sample. Patients were unblinded and more heterogenous than those included in most controlled clinical trial samples.Conclusions: This replication study in an independent community-based ketamine clinic sample revealed similar response trajectories, with only about a third of depressed patients benefitting substantially from an acute induction course of ketamine infusions.