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Psych Congress NetworkKetamine Treatment in TRD Should Last 4 Weeks or More for Antidepressant Benefit

Previous trials suggested that intravenous racemic ketamine was effective, but phase 3 trials were necessary to confirm the findings.


The use of subcutaneous racemic ketamine for treatment-resistant depression (TRD) has been thoroughly investigated in a study led by Dr. Colleen Loo. Conducted in Australia and New Zealand, the study explored the efficacy and safety of a 4-week course of this treatment method among TRD patients, comparing flexible-dose versus fixed-dose approaches and analyzing practical implications for the future.

Key Points:

  • The study assessed the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine for TRD, with a double-blind, randomized, active-controlled trial design.
  • Midazolam was chosen as the active control drug, and ketamine’s efficacy was found to be dose-related.
  • Two cohorts were compared: fixed-dose (cohort 1) and flexible response-guided dosing (cohort 2), with the latter showing significant antidepressant efficacy.
  • Cohort 1 did not yield significant results due to an insufficient dose.
  • A prototype of the Ketamine Side Effect Tool (KSET) was used to monitor safety comprehensively, with no notable concerns identified.

Additional Points:

  • The study emphasizes the importance of individualized, response-guided dosing and an adequate dose for efficacy.
  • It also highlights the necessity for ongoing treatment beyond 4 weeks to maintain antidepressant effects.
  • Long-term effects of ongoing ketamine treatment still require careful monitoring and data collection.

Conclusion:

  • The study’s findings present subcutaneous ketamine as a practical and safe treatment option for TRD, especially when individualized dosing approaches are employed, and emphasize the need for ongoing treatment and careful monitoring.

“Our study used a very comprehensive and detailed approach to monitor safety. Many studies have reported on the safety of ketamine in the 2 hours after each treatment, but our study also examined for cumulative effects over multiple treatments—this is important because the longer-term effects (eg, on the bladder lining) are different from short-term effects in the 2 hours after dosing.”

Colleen Loo, MBBS (Hons), FRANZCP, MD (research doctorate)
Clinical Psychiatrist and Professor of Psychiatry
University of New South Wales and the Black Dog Institute
Sydney, Australia
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