How to Select Outpatients for Ketamine Induction in Severe TRD
How should clinicians identify appropriate outpatients with severe treatment-resistant depression for an induction course of ketamine-based treatment?
Patients with major depressive disorder who remain severely depressed after multiple antidepressant trials may be considered for ketamine-based treatment in specialized outpatient settings. This guide summarizes the patient selection and induction-monitoring workflow actually used in the reported ketamine service for severe treatment-resistant depression.
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Confirm treatment-resistant major depression
Establish that the patient meets DSM-5 criteria for major depressive disorder. Confirm treatment resistance by documenting failure of at least 2 adequate antidepressant treatment trials, as required for inclusion in this cohort.
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Quantify baseline symptom severity with QIDS-SR16
Administer the 16-item Quick Inventory of Depressive Symptomatology Self-Report before treatment starts. Use a pretreatment score of 16 or higher to identify patients with severe depression matching the study population.
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Restrict treatment to eligible outpatients
Use this workflow for patients treated in an outpatient subspecialty setting. Exclude cases in which treatment is occurring while the patient is an inpatient, because those patients were not part of the study sample.
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Screen for service-level exclusions
Do not proceed if the patient has a history of psychosis, concerning substance use, or relevant uncontrolled medical illness. The article specifically lists recent myocardial infarction, aneurysmal disease, and arteriovenous malformations as examples of medical conditions that made patients ineligible.
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Choose an 8-treatment induction schedule
Plan 8 treatments administered twice weekly over 4 to 5 weeks, because this was the induction structure used for both treatment arms. Continue to collect QIDS-SR16 ratings at baseline and at each subsequent visit to track symptom change across the course.
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Apply route-specific administration and monitoring procedures
For IV racemic ketamine, start at 0.5 mg/kg infused over 40 minutes, with gradual conservative escalation permitted up to 1.0 mg/kg, and monitor the patient in clinic for at least 90 minutes after initiating each infusion. For intranasal esketamine, most patients start at 56 mg with prompt escalation to 84 mg, while monitoring blood pressure, heart rate, oxygen saturation, and respiration rate during treatment.
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Use functional discharge criteria after intranasal esketamine
Before discharge after intranasal esketamine, confirm return to baseline mental status, absence of gait disturbance, and normalizing blood pressure. In addition, instruct the patient not to drive until the following day.
Clinical Considerations
- This workflow comes from a retrospective chart review in a specialized outpatient ketamine service rather than a randomized protocol.
- Patients were allowed to continue or modify antidepressants and psychotherapy during treatment, so outcomes cannot be attributed solely to ketamine or esketamine exposure.
- The IV ketamine arm allowed conservative dose escalation up to 1.0 mg/kg, which complicates direct comparison with the fixed intranasal esketamine approach.
Bottom Line
In this report, ketamine-based induction was applied to carefully selected outpatients with DSM-5 major depressive disorder, at least 2 failed antidepressant trials, QIDS-SR16 scores of 16 or higher, and no psychosis, concerning substance use, or relevant uncontrolled medical illness.
