Ketamine for the Treatment of Opioid Use Disorder and Depression
Randomised, parallel-group Phase II study (n=21 actual) testing intranasal ketamine (60 mg) twice weekly for 4 weeks versus saline placebo in patients with co-occurring opioid use disorder on buprenorphine and treatment-resistant major depressive disorder.
Detailed Description
This parallel, randomised, triple-masked Phase II trial compares intranasal ketamine hydrochloride (60 mg) to saline placebo administered twice weekly for four weeks in participants on buprenorphine with opioid use disorder and comorbid treatment-resistant major depressive disorder.
Primary aims are to evaluate whether adjunctive ketamine improves treatment outcomes for opioid addiction and depressive symptoms; assessments include MADRS, OUD criteria, safety monitoring, and urine drug screens over an ~8-week participation period.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
Ketamine
experimentalIntranasal ketamine hydrochloride, twice weekly for four weeks.
Interventions
- Ketamine60 mgvia Other• twice per week• 8 doses total
Intranasal administration, 8 total doses over 4 weeks
Placebo
inactiveIntranasal saline placebo, twice weekly for four weeks.
Interventions
- Placebovia Other• twice per week• 8 doses total
Saline intranasal placebo, 8 total doses over 4 weeks
Participants
Inclusion Criteria
- Inclusion Criteria:
- 1. Between the ages of 18 to 65 years old.
- 2. Able to provide informed consent.
- 3. Meet DSM-5 criteria for Major Depressive Disorder, without psychotic features.
- 4. Score at least 20 on the Montgomery-Asberg Depression Rating Scale.
- 5. Fulfill a minimum of 4 of 11 current opioid use disorder criteria by DSM-5.
- 6. Have used opioids illicitly at least once in the past month.
- 7. Subjects must be on standard of care pharmacotherapy for OUD (buprenorphine) for at least one month.
- 8. Subjects taking other psychotropic medications (e.g. antidepressants or non-benzodiazepine anxiolytics) must be maintained on a stable dose for at least four weeks before study initiation.
- 9. Subjects must be considered to have treatment-refractory MDD as evidenced by failure or only partial response to treatment with at least two standard of care pharmacotherapy antidepressants.
- 10. Must consent to random assignment to intranasal ketamine or placebo control.
Exclusion Criteria
- Exclusion Criteria:
- 1. Immediate suicide risk (by Columbia Suicide Severity Rating Scale score of 4 or greater), a history of a suicide attempt in the past year, or by clinician judgment; likely to require hospitalization during the course of the study.
- 2. Self-reported history of illicit ketamine use, or baseline urine drug testing positive for ketamine.
- 3. In acute opioid withdrawal (as evidenced by a score of 5 or above on the Clinician Opioid Withdrawal Scale).
- 4. Meet DSM-5 criteria for current bipolar disorder.
- 5. Meet DSM-5 criteria for current or history of psychotic spectrum disorders.
- 6. Women who are pregnant or nursing.
- 7. Current hypertension as defined by systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg.
- 8. Self-reported history of delirium for any cause.
- 9. History of allergic or other adverse reaction to ketamine.
- 10. Clinically significant abnormal laboratory values, physical exam findings or medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g., glaucoma, brain aneurysms, cardiovascular disease, or end-stage renal disease).
- 11. Electrocardiogram findings (obtained within thirty days prior to randomization) of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction.
Study Details
- StatusCompleted
- PhasePhase II
- Typeinterventional
- DesignRandomizedtriple Blind
- Target Enrollment21 participants
- TimelineStart: 2020-12-17End: 2022-12-01
- Compounds
- Topic