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How Dosing of Ketamine affects Treatment for Depressed Patients

Updated: Apr 18


The results of a new clinical trial with ketamine were published in Nature’s Molecular Psychiatry journal.  Researchers conducted a double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).  99 subjects, 18-70 years old with TRD (defined as having less than 50% improvement in depression symptoms with conventional therapies) were randomized into one of five arms: a single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine 0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg (active placebo) (n = 19).


The authors found that the 0.5 and 1.0 mg/kg doses of ketamine were superior to the active placebo comparator, supporting its use as a novel antidepressant therapy.  Interestingly, the lower doses that were tested did not separate from the placebo comparator.  This is study is incredibly important because previously no dose range finding studies have been conducted with ketamine in patients with TRD.  Their data suggests that clinicians who use lower doses of ketamine may not see any significant clinical response.  This is typical of most drugs and is an important step toward developing the ideal dosing regimen that balances clinical benefit and risk.

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