Ongoing Challenges in Treating Hard-to-Treat Depression After Ketamine's Initial Effects

Rapid antidepressant effects from ketamine can occur within hours for treatment-resistant depression.

• The introduction of ketamine has shifted the focus from achieving short-term symptom relief to addressing post-response challenges.
• Key questions involve the durability of initial benefits and strategies for preventing relapse.
• Understanding how to structure and taper maintenance treatment is critical for long-term management.
• There is uncertainty about whether symptom improvement leads to functional recovery.
• Identifying patient characteristics that predict response remains problematic, as reliable biomarkers are still lacking.
• Concerns about the long-term safety and potential for abuse of repeated glutamatergic treatments are ongoing.

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