NCT05004896

Ketamine for Treatment-Resistant Bipolar Disorder

Repeated Ketamine Infusions for Treatment-Resistant Bipolar Disorder: A Randomized, Double-blind, Midazolam-controlled, Phase II Clinical Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 71 (actual)
• Sponsor: Joshua Rosenblat · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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 Ontario Shores Centre for Mental Health Sciences), 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).

Conditions

• Bipolar Disorder
• Bipolar Depression
• Bipolar I Disorder
• Bipolar II Disorder

Interventions

Type	Name	Description
DRUG	Ketamine Hydrochloride	36 patients will receive ketamine hydrochloride, over four infusions, flexibly dosed between 0.5 mg/kg to 0.75 mg/kg
DRUG	Midazolam Hydrochloride	36 patients will receive midazolam hydrochloride, over four infusions, flexibly dosed between 0.02 mg/kg to 0.03 mg/kg

Timeline

• Start date: 2022-07-04
• Primary completion: 2025-11-14
• Completion: 2025-11-14
• First posted: 2021-08-13
• Last updated: 2026-03-05

Locations

3 sites across 1 country: Canada