Ketamine for Treatment-Resistant Bipolar Depression
(KET-BD-Sustain Trial)
Trial Summary
What is the purpose of this trial?
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 RCTs have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with treatment-resistant bipolar disorder depression (TRBD). The primary research goal is to determine the acute antidepressant efficacy, safety and tolerability of repeated sub-anesthetic maintenance doses of IV ketamine in, over a period of twelve weeks. Open-label ketamine infusions will be provided on a flexible schedule (every 2-4 weeks) with flexible dosing (0.5-1.0mg/kg over 40 minutes) titrated to optimize benefits, while minimizing the dosage and frequency over a 12-week extension period. All patients participating in this open-label study will have completed an acute course of infusions in a parent two-site, phase II, double-blinded midazolam-controlled RCT trial. In addition to this acute course of four infusions, a maximum of six infusions will be provided over the 12-week period. 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), single-arm, open label, 12-week extension trial evaluating the effects of flexibly-dosed adjunctive ketamine infusions for TRBD to maintain antidepressant effects in participants who achieved an antidepressant response (MADRS decrease by \>50%) or remission (MADRS \< 12) following an acute course of four ketamine infusions is proposed. The primary outcome will be Montgomery-Åsberg Depression Rating Scale (MADRS) scores, determining by a linear mixed model from baseline to week 12. 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.
Will I have to stop taking my current medications?
The trial requires that you continue taking your current mood stabilizer medication without changes for at least a month before starting. However, you cannot use certain medications like benzodiazepines, monoamine oxidase inhibitors, stimulants, or cannabis during the trial.
What data supports the effectiveness of the drug Ketamine Hydrochloride for treatment-resistant bipolar depression?
Is ketamine safe for humans?
How is ketamine different from other drugs for treatment-resistant bipolar depression?
Ketamine is unique because it works quickly to relieve depression symptoms and suicidal thoughts by blocking a specific brain receptor (N-methyl-D-aspartate subtype glutamate receptor), and it is given through an IV (intravenous) infusion, which is different from most other depression treatments that are taken as pills.1671112
Research Team
Joshua Rosenblat, MD, MSc
Principal Investigator
Toronto Western Hospital, Psychiatry
Eligibility Criteria
Adults aged 21-65 with treatment-resistant bipolar depression, who've had no medication changes in the last month and are on a mood stabilizer. They must have participated in an earlier trial phase, responding well to ketamine or still depressed after midazolam control. No recent manic episodes, uncontrolled blood pressure, heart issues, severe liver/renal impairment, pregnancy/breastfeeding without contraception use, certain drug allergies or substance misuse.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive open-label ketamine infusions on a flexible schedule to maintain antidepressant effects
Follow-up
Participants are monitored for safety and effectiveness after treatment
Open-label extension
Participants continue to receive ketamine infusions to maintain antidepressant effects
Treatment Details
Interventions
- Ketamine Hydrochloride
Find a Clinic Near You
Who Is Running the Clinical Trial?
Joshua Rosenblat
Lead Sponsor
University Health Network, Toronto
Lead Sponsor