Ketamine Therapy for Treatment-Resistant Depression

What the Evidence Says About Ketamine for Treatment-Resistant Depression

Treatment-resistant depression — commonly defined as depression that has not improved after adequate trials of at least two antidepressants — is the condition with the strongest ketamine evidence base and the only psychiatric indication with an FDA-approved ketamine-derived medication. The FDA label for Spravato (esketamine) lists "treatment-resistant depression (TRD) in adults as monotherapy or in conjunction with an oral antidepressant" as an approved indication.

Spravato is dispensed only through certified centers: per its label, "SPRAVATO is available only through a restricted program under a REMS called the SPRAVATO REMS," with in-office monitoring after each dose. NIMH-funded research laid the groundwork for this class of medication, finding rapid symptom reduction in patients "for whom other treatments have not worked." Clinics in this directory that hold Spravato REMS certification display a badge on their listing.

FDA status: Spravato (esketamine) is FDA-approved for treatment-resistant depression — as monotherapy or with an oral antidepressant. IV/IM ketamine for TRD is off-label.

Sources:

• FDA prescribing information for Spravato (esketamine)
• NIMH — New Hope for Rapid-Acting Depression Treatment (2024)

Related Reading

• IV Ketamine vs. Spravato: What's the Difference?
• Does Spravato Work for Depression?
• Spravato Cost and Insurance Coverage