Ketamine for Treatment-Resistant Bipolar Disorder

This Phase II interventional trial (n=100) will assess the efficacy, safety, and tolerability of repeated sub-anaesthetic doses of intravenous ketamine for the treatment of moderate to severe treatment-resistant bipolar disorder (TRBD).

Conducted by the University Health Network, Toronto, the study aims to determine the acute antidepressant effects of four flexibly-dosed adjunctive ketamine infusions over two weeks. Participants, aged 21 to 65, diagnosed with Bipolar I or II Disorder and experiencing a Major Depressive Episode without psychotic features, will receive either ketamine or midazolam infusions.

The primary outcome measure will be the change in depression severity assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) scores after two weeks. Secondary outcomes include evaluating response and remission rates, safety, tolerability, effects on suicidality, anxiety, quality of life, function, and duration of effects. Recruitment began in April 2022, with an estimated completion date of April 2024.

Trial Details

Growing evidence has supported rapid and robust antidepressant effects with subanesthetic doses of intravenous (IV) ketamine for treatment resistant depression (TRD). However, no completed or ongoing randomized control trials (RCTs) have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with treatment-resistant bipolar disorder (TRBD). The primary research goal is to determine the acute antidepressant efficacy, safety and tolerability of four repeated sub-anesthetic doses of IV ketamine in moderate to severe TRBD. Secondary aims include evaluating effects of IV ketamine on suicidal ideations, quality of life, function and duration of effects. Herein, a two-site (University Health Network and Canadian Rapid Treatment Centre of Excellence), phase II, double-blinded, midazolam-controlled, two-week RCT evaluating the efficacy, safety and tolerability of four flexibly-dosed adjunctive ketamine infusions (0.5-0.75mg/kg infused over 40 minutes) for acute treatment of moderate to severe TRBD (type I & II) is proposed. The primary outcome will be Montgomery-Åsberg Depression Rating Scale (MADRS) scores, determining the between group difference in change from baseline to day 14, using analysis of covariance (ANCOVA), with 14-day MADRS as the outcome and baseline MADRS and stratification variables (sex, bipolar type) as covariates. Secondary outcomes include evaluating response and remission rates, safety, tolerability (including treatment-emergent mania), and effects on suicidality, anxiety, quality of life, function and the duration of effects (to day 28).

NCT Number NCT05004896

Data attribution

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