Safety and Efficacy of 112 mg Intranasal Esketamine in Patients with Treatment-Resistant Depression: A Retrospective Observational Study from Outpatient Community Clinics

This retrospective study examined the safety and efficacy of 56, 84, and 112 mg intranasal (IN) esketamine via medical record review of 24 patients with treatment resistant depression (TRD). Doses ranged from 56 mg to 112 mg and were titrated across sessions to maximize individual response while considering tolerability. Treatment response was defined by reduction in average Patient Health Questionnaire-9 (PHQ-9) scores. Tolerability was defined by blood pressures at baseline, 40 minutes after, and 2 hours after drug administration. Patients ranged from 19 to 60 years old (average 38.87), and 15 (62.5%) were female. Patients received an average of 1 treatment at 56 mg, 21.65 treatments at 84 mg, and 21.87 treatments at 112 mg. Average baseline PHQ-9 was 19.38 (SD 4.07). Increasing esketamine doses were associated with a stepwise reduction in PHQ-9 (p=0.064, 0.002, 0.003 for 56mg, 84mg, and 112 mg treatments respectively). 112 mg treatments were associated with a 2.37 day longer interval between treatments compared to 84 mg (p<0.001). Average mean arterial pressures (MAP) before, 40 minutes after, and 2 hours after drug administration were not significantly higher in 84 mg treatments than in 56 mg treatments (p= 0.990, 0.993, 0.959 respectively). However, all three average MAP were significantly higher in 112 mg treatments than in 84 mg treatments (p= 0.034, 0.002, 0.005). No patients required adjunctive medication or dose reduction. Currently, the field is lacking data on the efficacy and tolerability of 112 mg IN esketamine, and this study offers practical clinical guidance for esketamine dosing.