60 Participants Needed

Ketamine for Treatment-Resistant Bipolar Depression

(KET-BD-Sustain Trial)

Recruiting at 3 trial locations
NR
LP
AC
DG
AB
Overseen ByAmer Burhan, MBChB, MSc
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Joshua Rosenblat
Must be taking: Mood stabilizers
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

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?

Research shows that ketamine, given through an IV, can quickly improve symptoms in people with treatment-resistant bipolar depression. It has been effective in reducing depression symptoms and has shown promise in managing anxiety and irritability in similar conditions.12345

Is ketamine safe for humans?

Research suggests that ketamine is generally safe and well-tolerated in patients with treatment-resistant depression, but there is limited data on its long-term safety and tolerability, especially in community-based settings.678910

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

JR

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

I have been diagnosed with Bipolar I or II and am currently having a major depressive episode without psychosis.
I was in the ketamine study for depression and either got much better or my symptoms mostly went away.
My current depression hasn't improved after trying two or more recommended treatments.
See 3 more

Exclusion Criteria

Lifetime history of ketamine use disorder
Presence of active suicidality, requiring involuntary inpatient treatment or recent suicide attempts within the past 3 months.
I have not had major neurological issues or strokes in the last year.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label ketamine infusions on a flexible schedule to maintain antidepressant effects

12 weeks
Every 2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive ketamine infusions to maintain antidepressant effects

12 weeks

Treatment Details

Interventions

  • Ketamine Hydrochloride
Trial Overview The study tests maintenance doses of IV Ketamine Hydrochloride over twelve weeks for those with bipolar depression not improved by standard treatments. Participants receive flexible dosing every 2-4 weeks after showing initial improvement from previous infusions. The focus is on sustained antidepressant effects and impact on quality of life and suicidal thoughts.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: KetamineExperimental Treatment1 Intervention
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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Joshua Rosenblat

Lead Sponsor

Trials
2
Recruited
160+

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+

Findings from Research

In a study of 66 patients with treatment-resistant bipolar depression, repeated intravenous ketamine infusions led to significant reductions in depressive symptoms, with an average decrease of 6.08 points on the Quick Inventory for Depression Symptomatology-Self Report-16 scale after four infusions.
The treatment was generally well tolerated, with only 4.5% of patients experiencing treatment-emergent hypomania, and no cases of mania or psychosis, indicating a favorable safety profile for ketamine in this population.
Real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression.Fancy, F., Rodrigues, NB., Di Vincenzo, JD., et al.[2023]
In a study of 201 adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD), intravenous (IV) ketamine significantly reduced symptoms of anxiety, irritability, and agitation in those with mixed features, indicating its effectiveness in treating these symptoms.
Participants with anxiety, irritability, and agitation (AIA) experienced greater reductions in overall depressive symptoms and suicidal ideation compared to those without AIA, suggesting that IV ketamine could be a rapid treatment option for adults with mood disorders presenting with mixed features.
The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder.McIntyre, RS., Lipsitz, O., Rodrigues, NB., et al.[2021]
Low-dose intravenous (IV) ketamine has been shown to be effective in the short term for patients with treatment-resistant unipolar or bipolar depression, but its antidepressant effects are typically short-lived, necessitating maintenance treatment after initial response.
There is a lack of controlled evidence to guide psychiatrists on the best practices for maintaining the benefits of ketamine treatment, highlighting the need for further research in this area.
Next-Step Treatment Considerations for Patients With Treatment-Resistant Depression That Responds to Low-Dose Intravenous Ketamine.Bobo, WV., Riva-Posse, P., Goes, FS., et al.[2021]

References

Real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression. [2023]
The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. [2021]
Next-Step Treatment Considerations for Patients With Treatment-Resistant Depression That Responds to Low-Dose Intravenous Ketamine. [2021]
A Systematic Review on the Efficacy of Intravenous Racemic Ketamine for Bipolar Depression. [2021]
The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine. [2022]
A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. [2022]
Intravenous Ketamine Infusions in Treatment-Resistant Bipolar Depression: An Open-Label Naturalistic Observational Study. [2022]
Ketamine safety and tolerability in clinical trials for treatment-resistant depression. [2022]
Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. [2022]
A preliminary study of adjunctive ketamine for treatment-resistant bipolar depression. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study. [2022]