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Ketamine + selegiline is a combination of two small molecule drugs used off-label in the management of treatment-resistant depression, particularly in patients who have failed or are unable to undergo electroconvulsive therapy. Ketamine is an NMDA receptor antagonist with rapid-acting antidepressant effects, while selegiline is a selective, irreversible monoamine oxidase B (MAO-B) inhibitor that increases synaptic dopamine and other monoamines. The combination has been explored in case series and small studies for its potential to provide both rapid symptom relief (via ketamine) and sustained improvement (via ongoing selegiline therapy). Both agents can increase blood pressure, and their combined use requires careful monitoring due to additive risks of hypertension and central nervous system effects[1][6][7]. There are no approved fixed-dose combination products; this regimen involves co-administration of the individual drugs.
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