Compared with intranasal esketamine, intramuscular ketamine demonstrated comparable effectiveness and safety for patients with treatment-resistant depression (TRD) at just a fraction of the cost, according to a
study published in
Psychiatric Research and Clinical Practice.
Why It’s Relevant
Intravenous ketamine is an effective treatment for TRD, but not many outpatient offices are equipped to administer IVs. Intranasal esketamine—which is FDA-approved as both a monotherapy and adjunct for TRD—is easy to administer but comes at a considerable cost to health care systems. Intramuscular ketamine injections may offer a cost-effective alternative, but the evidence base for this formulation of ketamine is lacking.
By the Numbers
- Researchers compared the outcomes of 179 veterans with TRD (average age of 45; 75% male) who received eight treatments of either intranasal esketamine (initiated at 56mg, titrated to 84mg) or intramuscular ketamine (initiated at 0.5mg/kg, titrated to 1mg/kg).
- Each group showed nearly identical reductions in depression symptoms; average Patient Health Questionnaire-9 scores dropped from 19.5 at baseline to 14.2 after treatment.
- Similarly, posttraumatic stress disorder symptoms showed nearly identical improvement in both groups.
- Safety outcomes were also comparable. There were five psychiatric hospitalizations in the esketamine group and none in the intramuscular ketamine group, though this difference was not statistically significant.
- The cost difference between the two medications was considerable. Eight treatments of intranasal esketamine cost $6,069 compared with $648 for intramuscular ketamine.
The Other Side
This study was observational, evaluating data from a Veterans Affairs (VA) health system that provided patients with intranasal esketamine from January 2020 to March 2022 before switching to intramuscular ketamine, potentially creating temporal biases—for example, only the esketamine phase was impacted by the COVID-19 pandemic. The cost analysis modeling is also only applicable to the VA or closely related systems where insurance coverage doesn’t play a major role in treatment decisions.
Takeaway Message
As a safe, effective, cost-efficient alternative to intranasal esketamine, intramuscular ketamine “represents a vital means for providers and healthcare systems to improve access to treatment for patients with TRD,” the researchers wrote.
Related Information
Source
Kush V. Bhatt, et al. Real-world effectiveness and cost-differential of intranasal esketamine versus intramuscular ketamine. Psychiatric Research and Clinical Practice. Published online July 2, 2026. doi:10.1176/appi.prcp.20260041