IM Ketamine May Match Esketamine For Depression, At A Lower Cost
A new real world study adds a practical question to the ketamine conversation. If two clinic based treatments appear to reduce depression symptoms at similar rates, how much should cost shape access? Researchers compared intramuscular ketamine with intranasal esketamine for people with treatment resistant depression.
Their finding was striking. IM ketamine was noninferior to esketamine on depression outcomes, while the cost comparison favored the lower cost option.
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An Overview
| Key takeaway | What it means |
|---|---|
| The study compared two clinic based options | Researchers looked at IM ketamine and intranasal esketamine in real world care. |
| IM ketamine performed similarly | It was noninferior to esketamine on depression symptom scores. |
| The PHQ 9 difference was tiny | The adjusted difference was 0.04 points, which is clinically negligible. |
| Cost may become a bigger access issue | Esketamine often brings higher drug and administration costs. |
| This was not a randomized trial | The results are useful, but they do not settle the comparison. |
Why The Route Matters
Ketamine treatment for depression now comes in several forms. Esketamine is the FDA approved nasal spray sold as Spravato. It is used under medical supervision and tied to a formal safety program.
Racemic ketamine is different. It contains both ketamine molecules and is FDA approved as an anesthetic. When clinicians use it for depression, that use is off label. It may be delivered by IV infusion, injection, lozenge or nasal spray, depending on the clinic model.
This study focused on intramuscular ketamine, which is given by injection into the muscle. That route is less discussed than IV ketamine, but many clinics use it because it is simpler to administer and does not require an infusion setup.
What The Study Found
The researchers evaluated real world outcomes for patients receiving IM ketamine or intranasal esketamine for treatment resistant depression.
They used the PHQ 9, a common depression symptom scale, to compare changes over treatment. The key result was that IM ketamine was noninferior to esketamine. The baseline adjusted difference was 0.04 points on the PHQ 9.
In plain terms, that is almost no difference at all.
That finding does not mean the two treatments are identical. It means that, in this analysis, depression outcomes were close enough that IM ketamine met the study’s noninferiority standard.
The Cost Question
The study also looked at cost over an eight treatment course. That part matters because access to ketamine based care often depends less on science than logistics.
Esketamine has FDA approval, REMS requirements and a defined clinical protocol. Those features can support insurance coverage in some cases. They can also add complexity.
IM ketamine is typically less expensive as a medication and may be operationally simpler for clinics. But because its psychiatric use is off label, coverage can be uneven or absent.
For patients, that can create a strange choice. The approved product may be more formally recognized. The off label option may be more affordable.
What This Does Not Prove
This was a real world study, not a randomized controlled trial. That limits what it can prove.
Patients may have differed in ways that affected outcomes. Clinics may have used different protocols. Insurance, diagnosis, severity and prior treatment history may also have shaped who received which option.
Still, real world studies answer questions that controlled trials often miss. They show what happens when treatments leave the research setting and enter ordinary practice.
The Bigger Picture
The study does not crown a winner. It does something more useful. It pushes the field toward a more practical conversation.
For treatment resistant depression, effectiveness matters. So do monitoring, safety, patient preference, cost and access. IM ketamine may not have the regulatory status of esketamine. But this analysis suggests it deserves serious attention in comparative care models.
The next step is stronger research. Patients need studies that compare routes, costs and outcomes with more precision. Clinicians need data that reflects how these treatments are actually used. And payers need to explain why similar outcomes can lead to very different levels of access.
