Ketamine for the Treatment of Opioid Use Disorder and Depression

Inclusion criteria

• Between the ages of 18 to 65 years old.
• Able to provide informed consent.
• Meet DSM-5 criteria for Major Depressive Disorder, without psychotic features.
• Score at least 20 on the Montgomery-Asberg Depression Rating Scale.
• Fulfill a minimum of 4 of 11 current opioid use disorder criteria by DSM-5.
• Have used opioids illicitly at least once in the past month.
• Subjects must be on standard of care pharmacotherapy for OUD (buprenorphine) for at least one month.
• Subjects taking other psychotropic medications (e.g. anti-depressants or non benzodiazepine anxiolytics) must be maintained on a stable dose for at least four weeks before study initiation.
• 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.
• Must consent to random assignment to intranasal ketamine or placebo control.

Exclusion criteria

They are considered an immediate suicide risk (by Columbia Suicide Severity Rating Scale of 4 or greater, a history of a suicide attempt in the past year, or by clinician judgment) or felt to be likely to require hospitalization during the course of the study.

• They have a self-reported history of illicit ketamine use, or baseline urine drug testing positive for ketamine.

• They are in acute opioid withdrawal (as evidenced by a score of 5 or above on the Clinician Opioid Withdrawal Scale). These subjects will be referred for clinical detoxification and pharmacotherapy induction. Subjects may be re-assessed for study eligibility after one month of treatment with a standard of care OUD pharmacotherapy.

• Subjects who meet DSM-5 criteria for current bipolar disorder. 5. Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders.

• Women who are pregnant or nursing. 7. Subjects with current hypertension as defined by a systolic blood pressure (SBP) >140 mmHg or a diastolic blood pressure (DBP) >90 mmHg.

• Subjects with a self-reported history of delirium for any cause. 9. A history of allergic or other adverse reaction to ketamine. 10. Clinically significant abnormal laboratory values, physical exam findings or self-reported 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).

• Electrocardiogram (ECG) findings (obtained within thirty days prior to randomization) of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction).