Phase II, double-blind, randomized, quadruple-masked RCT (n=72) testing four IV ketamine infusions (0.5–0.75 mg/kg over 40 minutes) versus midazolam (0.02–0.03 mg/kg) as adjunctive treatment for moderate to severe treatment-resistant bipolar depression.
This two-site (University Health Network and Ontario Shores) phase II double-blind randomised trial evaluates four repeated sub-anaesthetic IV ketamine infusions versus active midazolam comparator for acute treatment of moderate to severe treatment-resistant bipolar disorder (types I and II).
Ketamine is given at 0.5 mg/kg for the first two infusions with flexible dosing to 0.75 mg/kg for infusions 3–4, each infused over 40 minutes; midazolam is dosed 0.02–0.03 mg/kg on the same schedule.
Primary outcome is change in MADRS score from baseline to day 14; secondary outcomes include response/remission rates, safety and tolerability (including treatment-emergent mania), suicidality, anxiety, quality of life, function and durability of effect to day 28.
Four IV infusions over two weeks; first two at 0.5 mg/kg, infusions 3–4 flexibly dosed 0.5–0.75 mg/kg depending on response.
Infused over 40 minutes; flexible dosing for infusions 3–4 (0.5–0.75 mg/kg).
Four IV midazolam infusions over two weeks as active comparator; first two at 0.02 mg/kg, infusions 3–4 flexibly 0.02–0.03 mg/kg.
Midazolam hydrochloride 0.02–0.03 mg/kg infused over 40 minutes (active comparator; recorded under notes).