Real-World Effectiveness and Cost-Differential of Intranasal Esketamine Versus Intramuscular Ketamine

This study evaluated whether intramuscular (IM) ketamine is non-inferior to intranasal (IN) esketamine for treatment-resistant depression (TRD) and assessed differences in safety and healthcare costs.

In a retrospective, observational sequential cohort at the VA San Diego, 179 Veterans with TRD received eight treatments of either IN esketamine (n = 89) or IM ketamine (n = 90). The primary outcome was change in depressive symptoms (PHQ-9) analyzed via linear mixed-effects models with a non-inferiority margin of -1.25 points. Secondary outcomes included Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 symptoms, adverse events, and a cost-difference analysis.

IM ketamine was non-inferior to IN esketamine for depression, with a baseline-adjusted estimated marginal mean PHQ-9 difference of 0.04 points (95% CI: -1.21 to 1.29). Reductions in PTSD symptoms were also non-inferior. Incidence of sentinel adverse events were comparable, with no significant differences in emergency department visits or hospitalizations. Cost analysis revealed a significant disparity: the total cost per eight-treatment course was $6069 for IN esketamine versus $647 for IM ketamine, with this difference driven primarily by the cost of IN esketamine.

IM ketamine demonstrated comparable clinical effectiveness and safety to FDA-approved IN esketamine while offering a significant reduction in cost. These findings suggest IM ketamine may be a high-value alternative to IN esketamine that could significantly expand access to psychiatric care for individuals with TRD.

These findings provide real-world evidence supporting the use of IM ketamine for TRD, and suggests that this formulation could offer a pathway for improving access to ketamine treatment by lowering the cost to healthcare systems.