Real-World Effectiveness of Repeated Ketamine Infusions for Treatment-Resistant Bipolar Depression

Abstract

Background: Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression.

Methods: This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment-resistant bipolar I/II depression (n = 66) received four sub-anesthetic doses of IV ketamine (0.5-0.75 mg/kg) over a two-week period. Symptoms of depression, suicidality, anxiety, and functioning were assessed with validated self-report measures.

Results: Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR₁₆) with further reductions in depressive symptoms observed after each subsequent infusion (n = 66; mean QIDS-SR₁₆ reduction of 6.08+/-1.39; p < 0.0001). Significant reductions of suicidal thoughts (QIDS-SR₁₆-Suicide Item) and anxiety (Generalized Anxiety Disorder-7) were also observed with functional improvements on the Sheehan Disability Scale (p < 0.0001 on all measures). Moreover, the response rate (QIDS-SR₁₆ total score decrease ≥50% from baseline) was 35% and remission rate (QIDS-SR₁₆ total score ≤5) was 20% after four infusions. Infusions were generally well tolerated with treatment-emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis.

Conclusions: Real-world effectiveness of IV ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability.Reprinted from Bipolar Disord 2023; 25:99-109, with permission from John Wiley and Sons. Copyright © 2023.

Keywords: bipolar disorder; depression; effectiveness; efficacy; esketamine; function; ketamine; major depressive disorder; patient-reported outcomes; quality of life.