A proportion of individuals with
major depressive disorder (MDD) do not receive adequate therapeutic benefit from conventional monoaminergic
antidepressant drugs, leading to
treatment-resistant depression (TRD).
Ketamine has been shown to provide rapid and significant efficacy in treating patients with TRD. The majority of published studies have investigated the adjunctive efficacy of
ketamine with one or more monoaminergic
antidepressants. There remains a clinical need to ascertain the relative effectiveness of
ketamine monotherapy versus adjunctive
ketamine treatment in adults with TRD. In this retrospective study, we investigate multidimensional, self-reported outcomes (i.e.,
antidepressant, anti-suicidality, antianxiety, and anti-functional impairment) of 220 patients to compare monotherapy (n = 39) and adjunctive (n = 181)
ketamine treatment for TRD at a community-based clinic. Both groups had clinically and statistically significant
antidepressant effects (p < 0.05). Individuals receiving
ketamine monotherapy exhibited a significantly greater reduction on the suicidal ideation (SI) item of the Quick Inventory for Depressive Symptomatology-Self Report 16-Item (QIDS-SR16) than the adjunctive group, with a small effect size [F (1, 265) = 4.73; p = 0.03*; partial η2 = 0.02], and a significantly higher proportion of partial responders at post-infusion 4 (p = 0.034*). No other between-group differences were significant. Limitations include the small sample, single-centred, open-label, non-randomized, uncontrolled, retrospective nature of this study and indication bias. Our real-world evidence suggests that
ketamine may be effective as monotherapy or adjunct to monoamine-based treatments. A priority research and clinical vista is to identify subsets of individuals with TRD who are most likely to have a desired therapeutic outcome with monotherapy versus adjunctive
ketamine treatment.