Ketamine infusions for bipolar depression treatment

Maintenance Ketamine Infusions for Treatment-Resistant Bipolar Depression: An Open-Label Extension Trial

This study is testing if regular ketamine infusions can help people with bipolar depression who haven't found relief from other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 65 Years
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Locations: 3 sites (Toronto, Ontario and 2 other locations)
• Trial ID: NCT05339074 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effects of repeated intravenous ketamine infusions on patients with treatment-resistant bipolar depression. Participants will receive sub-anesthetic doses of ketamine on a flexible schedule over a 12-week period, following an initial acute treatment phase. The study aims to assess the antidepressant efficacy, safety, and tolerability of this maintenance therapy in a homogenous group of patients. All participants will have previously shown a positive response to ketamine in an earlier randomized controlled trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 65 with a diagnosis of Bipolar I or II Disorder currently experiencing a Major Depressive Episode.

Not a fit: Patients who do not meet the criteria for treatment-resistant bipolar depression or those who have not responded to prior ketamine treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients suffering from treatment-resistant bipolar depression.

How similar studies have performed: Previous studies have shown promising results with ketamine for treatment-resistant depression, suggesting potential success for this approach in bipolar depression.

Eligibility criteria

Inclusion Criteria:

1. Provide written, voluntary informed consent prior to study enrollment. Substitute decision makers will not be allowed to consent to study on a potential patient's behalf.
2. Male or female between the age of 21 to 65, inclusive.
3. Meets DSM-5 criteria for Bipolar I or II Disorder, currently experiencing a Major Depressive Episode without psychotic features. Diagnosis confirmed by study psychiatrist at the start of the parent KET-BD randomized clinical trial (RCT).
4. Patients in the KET-BD RCT 4a. Patients in the ketamine arm of the KET-BD RCT must have experienced an antidepressant response (i.e. change in MADRS score ≥ 50% at day 14 compared to baseline or Clinical Global Impression-Improvement (CGI-I) = 2 'much improved' or 1 'very much improved') or experienced clinical remission of symptoms (i.e., MADRS score \< 12 on day 14) 4b. Patients in the midazolam arm of the KET-BD RCT must present as moderately to severely depressed (MADRS \>21) on days 14 and 28 of the parent RCT and must be responders or remitters following four flexibly dosed infusions over 2 weeks.
5. Current depressive episode has inadequate response to two or more adequate first-line treatment trials for bipolar depression, as per the 2018 CANMAT Bipolar Disorder Guidelines. First line treatment trials include the use of lithium, valproate, carbamazepine, lamotrigine and/or any antipsychotic medication. Adequate medications confirmed at the start of the parent KET-BD RCT.
6. Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month, including a therapeutic dose of a mood stabilizer.

Exclusion Criteria:

1. Currently exhibiting symptoms of mania, hypomania, or mixed state bipolar, as determined by the Young Mania Rating Scale (YMRS) score greater than 12.
2. Current symptoms of psychosis or a substance use disorder within the past 3 months. History of psychotic features during a mood episode will not be excluded.
3. History of neurological disorders (including, but not limited to, uncontrolled seizure disorder, history of stroke within past 12 months, major head injuries, aneurysmal vascular disease \[including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels\], arteriovenous malformation, or intracerebral hemorrhage)
4. Lifetime history of a primary psychotic disorder (including, but not limited to, schizophrenia or schizoaffective disorder)
5. Lifetime history of ketamine use disorder
6. Presence of active suicidality, requiring involuntary inpatient treatment or recent suicide attempts within the past 3 months.
7. Presence of a contraindication to ketamine, including a drug allergy, uncontrolled hypertension (baseline systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg), low or labile blood pressure, myocardial infarction within past 12 months, cardiac arrhythmia, moderate to severe hepatic impairment (i.e., Child-Pugh score of B or C), moderate or severe renal impairment (glomerular filtration rate (GFR) \< 45 milliliters/min), heart failure, or coronary artery disease
8. Pregnant or breastfeeding women or women who intend to get pregnant. Patients who are sexually active must agree to use a highly effective contraceptive method (as outlined in section 5.9).
9. Use of prohibited concomitant medications, including other forms of ketamine or esketamine, benzodiazepines, monoamine oxidase inhibitors, stimulants, medical or recreational cannabis of any form.
10. Patients in the ketamine-arm of the parent RCT, that did not reasonably tolerate 4 infusions of flexibly-dosed ketamine, as determined by the investigator and/or patient

Where this trial is running

Toronto, Ontario and 2 other locations

• Toronto General Hospital — Toronto, Ontario, Canada (Recruiting)
• Toronto Western Hospital — Toronto, Ontario, Canada (Recruiting)
• Ontario Shores Centre for Mental Health Sciences — Whitby, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Joshua Rosenblat, MD, MSc — Toronto Western Hospital, Psychiatry
• Study coordinator: Anesthesia Clinical Trials Unit

Conditions Bipolar Disorder; Bipolar Depression; Bipolar I Disorder; Bipolar II Disorder