Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Real-World Setting Among Patients with Treatment Refractory Depression

Abstract

BACKGROUND Ketamine, an N-methyl-d-aspartate receptor antagonist, has been "repurposed" as a rapid-acting antidepressant for treatment-resistant depression (TRD). The s-enantiomer of ketamine, "esketamine," was FDA approved for TRD and depressive symptoms in adults with major depressive disorder with suicidal ideations/behaviors. Intravenous (IV) ketamine, although financially less expensive, is often not covered by insurance and intranasal (IN) esketamine, although covered by insurance can be expensive. There is a paucity of literature on efficacy data comparing subanesthetic IV ketamine and IN esketamine for TRD in a real-world scenario. Thus, we conducted this study comparing the efficacy and the number of treatments required to achieve remission/response with repeated use of subanesthetic IV ketamine/IN esketamine among TRD patients. METHODS This was an observational study where we included adults (≥18 years) with TRD who provided consent and had received up to 6 IV ketamine infusions (0.5 mg/kg, infused over 40 minutes) or up to 8 intranasal (IN) esketamine (56/84 mg) treatments for TRD at the Mayo Clinic Depression Center. Depression symptoms were measured utilizing the self-report 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale before and 24 hours after ketamine/esketamine treatment. Remission and response were defined as QIDS-SR 16 score ≤5 and ≥50% change in QIDS-SR 16, respectively. Continuous variables are reported as means ± SD and categorical variables as counts and percentages. The Wilcoxon rank-sum test was used to compare continuous variables. Chi-square and Fisher's exact tests were used to compare categorical variables. The number of treatments to remission/response was calculated. RESULTS Sixty-three adults with TRD, middle-aged (47.0 ± 12.1 years), predominantly female (65%), of which 76% (n = 48) and 24% (n = 15) received IV ketamine and IN esketamine, respectively. Mean (SE) change in QIDS-SR 16 score was -8.7 ± 0.7 (P.05). The mean number of treatments received to achieve response (2.5 ± 1.6 vs 4.6 ± 2.1) and remission (2.4 ± 1.3 vs 6.3 ± 2.4) were significantly lower among patients who received IV ketamine compared to IN esketamine (P