Can talk therapy boost ketamine for dual diagnosis?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Provision of written informed consent after reading and understanding the patient information handout * Alcohol Use Disorder (AUD) diagnosed by a trained psychiatrist * Diagnosis of treatment resistant unipolar or bipolar depression, defined as failure to respond to ≥2 adequate trials per Canadian national depression guidelines * Willingness to engage in 8 weekly psychotherapy sessions * No changes to psychotropic medications during treatment * Average daily ethanol consumption of at least moderate risk as per WHO risk levels (Men: \>40 to 60 g per day or \>2.9 to 4.3 drinks / Women: \>20 to 40 g per day or \>1.4 to 2.9 drinks) * Bipolar or unipolar depressive episode (DSM5), current episode, with MADRS ≥ 20 * Age 18 to 70 years * Agreement to abstain from consuming grapefruit juice on ketamine infusion days * Agreement to abstain from driving or operating heavy machinery after infusions until the next day Exclusion Criteria: * Current participation in other evidence based psychotherapeutic interventions for mood disorders or substance abuse * Inability to commit to the study protocol due to professional or personal obligations * Non English or non French speaking * Psychiatric comorbidity likely to take precedence over AUD or TRD * Acute psychotic disorder or acute psychotic symptoms * Current or prior substance abuse or dependence other than AUD (except caffeine or nicotine) * Non response to esketamine or ketamine during the current depressive episode * Known intellectual disability or autism spectrum disorder * Inability to attend regular visits to the CHUM Neuromodulation clinic * Depression secondary to stroke, cancer, or severe medical conditions * Risk factors for intracranial hemorrhage (trauma, aneurysm, neurosurgery) * Uncontrolled hypertension or significant coronary or cerebrovascular disease * Renal or hepatic impairment * Pregnant, lactating, or of childbearing potential without approved contraception use during ketamine treatment, with a negative urine pregnancy test required at baseline * Abnormal liver function tests (AST or ALT ≥ 3 times upper normal limit) * Clinically significant abnormal ECG results * Unstable thyroid hormone levels or uncorrected hypo or hyper thyroidism * Any unstable or clinically significant condition judged by the study physician to interfere with treatment * Positive toxicology screen for drugs not prescribed * Unwillingness to abstain from benzodiazepines, narcotics, or NMDA antagonists (including memantine and lamotrigine) 12 hours before infusions * Known intolerance or hypersensitivity to ketamine * Significant hearing impairment not improved by aids * Any recent significant decline in exercise tolerance