Evaluating the effectiveness of ketamine therapy on depressive symptoms in Veterans: A program evaluation

Abstract: Background: Veterans experience disproportionately high rates of depression and comorbid PTSD, often with treatment resistance (Nitcher et al., 2019). Rapid-acting interventions such as racemic ketamine have demonstrated clinically meaningful reductions in depressive symptoms in controlled and real-world studies (Liu et al., 2024). Purpose: Evaluated changes in depressive symptoms among veterans completing a standard six-session ketamine program in a private outpatient clinic, using pre- and post-treatment PHQ-9 total and item-level scores. Methods: Retrospective review of PHQ-9 total and item-level scores in adult veterans who completed six ketamine treatments (IV or IM) between January 1 and August 31, 2025, with PHQ-9s obtained ≤7 days pre-treatment and ≤7 days after the sixth session. Primary outcome: change in PHQ-9 total; secondary: item-level change trends. Results: Among 20 veterans (mean age = 53.5 years; 65% male), mean PHQ-9 scores decreased from 17.0 (SD = 5.76) at baseline to 12.5 (SD = 6.99) post-treatment, a mean change of −4.5 points (95% CI [−6.68, −2.32]; p = .0007; Cohen’s d = −0.91). Overall, 35% achieved clinical response (≥50% reduction in PHQ-9), 10% met criteria for remission (PHQ-9 < 5), and 45% experienced a ≥5-point improvement. Item-level analyses showed significant reductions in anhedonia, depressed mood, sleep disturbance, fatigue, concentration difficulties, and psychomotor symptoms, with a non-significant but clinically relevant reduction in suicidal ideation (PHQ-9 Item 9 endorsement from 30% to 20%). Conclusions: Completion of a six-session ketamine program in this community clinic was associated with statistically and clinically meaningful reductions in depressive symptoms among veterans, with improvement across multiple symptom domains and a numerical decrease in suicidal ideation. These preliminary findings support ketamine therapy as a promising, measurement-based intervention for veterans with moderate to severe depressive symptoms and highlight the value of ongoing program evaluation to optimize real-world implementation.