Clinical TrialBipolar DisorderKetamineRecruiting

Maintenance Ketamine Infusions for Treatment-Resistant Bipolar Depression

This open-label trial (n=60) aims to assess the efficacy and safety of repeated subanesthetic maintenance doses of intravenous (IV) ketamine in patients with treatment-resistant bipolar depression (TRBD) over a period of twelve weeks.

Target Enrollment
60 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed Description

Open-label, single-arm 12-week extension (n=60) of a parent double-blind RCT testing flexible adjunctive IV ketamine infusions for participants with treatment-resistant bipolar depression who responded or remitted after an acute course.

Flexible dosing between 0.5–1.0 mg/kg administered over 40 minutes, given on a flexible schedule every 2–4 weeks with up to six infusions over 12 weeks; primary outcome is change in MADRS from baseline to week 12.

Secondary outcomes include response and remission rates, safety and tolerability (including treatment-emergent mania), suicidality, anxiety, quality of life, function and duration of antidepressant effects.

Study Protocol

Preparation

0 sessions

Dosing

6 sessions
40 min each

Integration

0 sessions

Study Arms & Interventions

Ketamine

experimental

Open-label, single-arm flexible maintenance IV ketamine infusions (adjunctive) for TRBD participants who responded/remitted to an acute course.

Interventions

  • Ketamine0.5 - 1 mg/kg
    via IV• flexible (every 2-4 weeks)• 6 doses total

    Infusions 0.5–1.0 mg/kg administered over 40 minutes; flexible titration up to 6 infusions over 12 weeks; participants must have responded (≥50% MADRS) or remitted (MADRS <12) after acute course.

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion 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

  • 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 (GFR < 45 mL/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.
  • 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 who did not reasonably tolerate 4 infusions of flexibly-dosed ketamine, as determined by the investigator and/or patient.

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment60 participants
  • Timeline
    Start: 2022-08-10
    End: 2024-08-31
  • Compound
    Ketamine
  • Topic
    Bipolar Disorder

Locations

Toronto General Hospital — Toronto, Ontario, Canada
Toronto Western Hospital — Toronto, Ontario, Canada
Ontario Shores Centre for Mental Health Sciences — Whitby, Ontario, Canada

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