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Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant
Duncan George1, Verònica Gálvez1, Donel Martin1
1School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia; Black Dog Institute, Sydney, New South Wales, Australia.
Objective:
To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment.
Methods:
In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months.
Results:
Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse.
Conclusion:
Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection is a practical method for giving ketamine. Repeated treatments may improve remission rates (clinicaltrials.gov; NCT01441505).
