Objective:

To compare the real-world effectiveness of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression (TRD) in a community psychiatric setting.

Approach:

• Study Design: Single-center retrospective cohort study of adults aged 18 to 65 receiving induction therapy for TRD with intranasal esketamine or IV ketamine.
• Inclusion Criteria: Adults aged 18 to 65 with no prior exposure to either medication or oral ketamine derivatives.
• Primary Outcome: Change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to end of induction.
• Secondary Outcomes: Response (≥50% PHQ-9 reduction), remission (final PHQ-9 ≤4), clinically meaningful improvement (≥5 PHQ-9 reduction), induction completion, and adverse events.

Key Findings:

• Sixty-three patients met inclusion criteria (esketamine n=37; IV ketamine n=26).
• Baseline PHQ-9 scores were similar between groups (18.22 vs. 18.27; P = 0.967).
• Mean change in PHQ-9 scores was -10.31 for esketamine and -9.50 for IV ketamine (P = 0.589).
• Response rates were 64.9% for esketamine and 69.2% for IV ketamine (P = 0.790).
• Remission rates were 32.4% for esketamine and 23.1% for IV ketamine (P = 0.573).
• Induction completion exceeded 90% in both groups, with one patient per cohort discontinuing due to side effects.

Interpretation:

Limitations:

• Modest sample size limits power to detect between-group differences.
• Protocol asymmetry between treatment arms affects direct comparison of outcomes.

Conclusion: