In Esketamine and IV Ketamine: Multi-site Observational Study Assessing the Effectiveness and Tolerability of Two Novel Therapies for Treatment-resistant Depression.

This is a multi-center observational prospective cohort study in Providence Care Hospital in Kingston, ON; Envision Mind Care in Edmonton, AB; Center for Addiction and Mental Health in Toronto, ON; the University of British Columbia in Vancouver, BC; and Sunnybrook Health Sciences Center in Toronto, ON, Canada. This study presents real-world clinical data from patients receiving either IV ketamine or IN esketamine for the management of MDD-TRD. Participants consisted of adult outpatients (18-75 years old) with unipolar depression experiencing major depressive episodes as determined by the DSM5 and characterized as MDD-TRD (diagnosed with major depressive disorder as outlined by the DSM5 and experienced at least two previous failed antidepressant treatments of adequate dose and duration for the current episode.

IV ketamine or IN esketamine are provided as standard-of-care, add-on treatments and free of charge to patients. Only medications that have the potential to interact with either ketamine or esketamine, such as benzodiazepines, naltrexone, lamotrigine, gabapentin and pregabalin, are discontinued prior to the start of the treatment and for the duration of treatment. The tapering and discontinuation processes follow the standard-of-care clinical practices and are monitored by the most responsible physician for each patient. Patients with psychosis, main diagnosis of personality disorder, uncontrolled hypertension, substance abuse, currently pregnant or breastfeeding, or who had a previous negative reaction to ketamine or esketamine, are ineligible to receive IV ketamine or IN esketamine.

Approval to perform this study was obtained through the Health Sciences Research Ethics Board at Queen's University (TRAQ #: 6031789). All participants provide voluntary, written informed consent for collecting, analyzing, and presenting aggregate data. This study follows the standards set by the Declaration of Helsinki, and data management complies with US federal Health Insurance Portability and Accountability Act (HIPAA) regulations pertaining to the confidentiality of patient records.

After obtaining informed consent from the participants, Investigators observe participant acute treatment course receiving either IV ketamine or IN esketamine treatment, recording any potential side effects during and after administration and changes in the severity of participant depressive symptoms. In the participating clinical centers, both IV ketamine and IN esketamine treatments consist of bi-weekly sessions for four weeks following standard-of-care clinical guidelines. The decision of delivering IV ketamine or IN esketamine is determined between the patient and the most responsible physician responsible for administering the treatment. Insurance coverage for IN esketamine and patient preference for mode of administration (IV vs IN) are major determinant factors. Since IN esketamine is approved by Health Canada, this is the preferred treatment if a patient has the appropriate insurance coverage, otherwise IV ketamine is offered for free as its cost is covered by the academic center providing the treatment.

For IV ketamine treatment, ketamine is administered at 0.5mg/kg over 40 minutes. For IN esketamine treatment, esketamine is administered as a nasal spray, two sprays per nostril (56mg total) for the first treatment and three sprays per nostril (84mg) for the rest of the acute series. All treatments are administered at the academic center under the supervision of a mental health care professional. Patients are asked to come fasting at least two hours prior to treatment and to remain resting in the treatment room throughout the dosing session. Throughout each dosing session, blood pressure, oxygen levels, and onset, duration and severity of common side effects are recorded by nursing staff and/or physicians. Patients are discharged after a minimum of 30 minutes post administration, provided that the vital signs return to baseline and that the patient is calm, alert, and oriented.