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

Abstract

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. This was an observational study where we included adults (≥18years) with TRD who provided consent and had received up to 6 IV ketamine infusions (0.5mg/kg, infused over 40minutes) or up to 8 intranasal (IN) esketamine (56/84mg) 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 24hours 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. 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<.001), a significant reduction (improvement) from baseline (mean±SD=17.6±3.7). Overall remission and response rates were 36.5% and 55.6%, respectively in the acute phase. Response (56.3% vs 53.3%) and remission rates (39.6% vs 26.7%) were similar among patients who received IV ketamine or IN esketamine, respectively (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<.005). Most patients tolerated both treatments well. Intravenous ketamine and intranasal esketamine showed similar response/remission in TRD patients but the number of treatments required to achieve response/remission was significantly lower with IV ketamine compared to IN esketamine. These findings need to be investigated in a randomized control trial comparing these two treatment interventions. No funding.