Key Takeaways

From the Authors As published in the article
  1. Intravenous (IV) ketamine has been shown to be effective for depression in short-term clinical trials; this study assessed longer-term outcomes among Veterans Health Administration patients treated under routine care conditions for up to 1 year.
  2. About one-fourth of patients achieved a 50% reduction in depression symptoms, and symptom improvement tended to plateau after 6 weeks of repeated infusions. Symptom improvement was maintained for several months as infusion frequency decreased from about twice weekly to every 3 to 4 weeks.
  3. Veterans who received IV ketamine had extensive prior antidepressant treatment use and high rates of comorbid posttraumatic stress disorder, alcohol and substance use disorders, and chronic pain, which may explain lower response rates compared to prior studies.
Extended Takeaways
  1. IV ketamine use in VA was highly concentrated: 19 facilities treated at least 1 patient, only 7 facilities treated 10 or more patients, and 50% of the patients were treated at the 2 highest volume facilities, which suggests access and program experience may vary substantially across sites.
  2. This cohort reflects severe, highly treatment-resistant depression rather than early-line use, with a baseline PHQ-9 of 18.6, 22% having prior-year psychiatric hospitalization, 13% prior rTMS, 18% prior ECT, and a mean of 6.1 different antidepressant trials in the past 20 years.
  3. Dosing and scheduling changed meaningfully over time in routine care, with mean ketamine dose increasing from 45 mg at the first infusion to 66 mg at patients’ last infusion while infusion intervals widened from 5 days in the first month to 23–28 days during months 5 to 12.
  4. Patients who improved typically did so after multiple treatments rather than after just a few infusions: among those who ever met criteria, mean time to MCID was 51 days and 9 infusions, and mean time to remission was 56 days and 10 infusions.
  5. At 6 weeks, the only factor linked to greater PHQ-9 improvement was treatment intensity, with a β coefficient of 0.7 (P = .002) for number of infusions, indicating each additional infusion was associated with a mean 0.7-point greater improvement in the 6-week PHQ-9 score.
  6. Comorbid posttraumatic stress disorder was common at 70%, yet demographic and diagnostic characteristics were not associated with 6-week PHQ-9 change, supporting IV ketamine as a consideration for complex major depressive disorder presentations that might respond less well to oral antidepressants or repetitive transcranial magnetic stimulation.
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