Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study

Objective: Ketamine has been redeveloped as a rapid-acting antidepressant for treatment-resistant depression (TRD). There is a paucity of literature comparing subanesthetic intravenous (IV) ketamine and US Food and Drug Administration (FDA)- approved intranasal (IN) esketamine for TRD in real-world clinical settings. We compared the efficacy and time to achieve remission/response with repeated ketamine and esketamine. Methods: An observational study of adults with TRD received up to 6 IV ketamine (0.5 mg/kg over 40-100 minutes) or up to 8 IN esketamine (56- or 84-mg) treatments from August 17, 2017, to June 24, 2021. Depressive symptoms were measured utilizing the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) before and 24 hours after treatment. Cox proportional hazard models were used to evaluate associations between time to response (= 50% change in QIDS-SR score) and remission (QIDS-SR score = 5). Results: Sixty-two adults (median age = 50 years, 65% female) received IV ketamine (76%, n = 47) or IN esketamine (24%, n = 15). Neither baseline-to-endpoint change in QIDS-SR score nor response/remission rates were significantly different between groups. Time to remission, defined as number of treatments (adjusting for age, body mass index, sex, and baseline QIDS-SR score), was faster for IV versus IN treatment (HR = 5.0, P = .02). Conclusions: Intravenous ketamine and intranasal esketamine showed similar rates of response and remission in TRD patients, but the number of treatments required to achieve 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.