IV Ketamine Protocol for Major Depressive Disorder
IV ketamine should be reserved for patients with major depressive disorder who have not responded to several adequate pharmacologic trials, with a recommended protocol of 0.5 mg/kg administered intravenously over 40 minutes. 1
Patient Selection
- Ketamine is not recommended as initial treatment for major depressive disorder but should be reserved for patients who have failed or not tolerated previous therapies 1
- Best candidates are those with treatment-resistant depression (TRD), defined as failure to respond to at least two adequate trials of antidepressant medications 1, 2
- Consider ketamine for patients with severe depression accompanied by suicidal ideation, as it has demonstrated rapid reduction in suicidal thoughts 1, 2
Dosing Protocol
- Standard dose: 0.5 mg/kg administered intravenously over 40 minutes 1, 2
- Administration should be performed by or under the direction of physicians experienced in administering general anesthetics and maintaining a patent airway 3
- For maintenance of antidepressant effect, ketamine can be administered by slow microdrip infusion at 0.1 to 0.5 mg/minute 3
Preparation and Administration
- For IV administration, the 100 mg/mL concentration must be properly diluted before use 3
- Dilute with an equal volume of either Sterile Water for injection, 0.9% Sodium Chloride Injection, or 5% Dextrose in Water 3
- Use immediately after dilution 3
- For maintenance infusions, prepare a dilute solution containing 1 mg of ketamine per mL by transferring 10 mL from a 50 mg/mL vial (or 5 mL from a 100 mg/mL vial) to 500 mL of appropriate diluent 3
Treatment Schedule
- Initial treatment typically involves a single infusion, with effects appearing within 24 hours and lasting 3-7 days 2, 4
- For sustained benefit, a series of 6 infusions administered three times weekly over a 12-day period has shown efficacy 5
- After initial series, maintenance infusions can be spaced out, with frequency decreasing from every 5 days to every 3-4 weeks over the first 5 months 6
Monitoring and Safety Considerations
- Continuous vital sign monitoring is essential during and immediately after infusion 3
- Emergency airway equipment must be immediately available 3
- Consider administering an antisialagogue prior to ketamine administration due to potential for increased salivation 3
- Monitor for psychotomimetic experiences, dissociative symptoms, and hypertension 2, 7
- Consider augmenting with a benzodiazepine to prevent neuropsychological manifestations during emergence 3
Expected Outcomes
- Rapid improvement in depressive symptoms can occur within hours to 1 day after infusion 2, 4
- Antidepressant effects typically last 3-7 days after a single infusion 1, 4
- When used as adjunctive therapy to ongoing antidepressant treatment, effects may persist longer than when used as monotherapy 1
- In clinical practice, approximately 26% of patients achieve response (50% improvement) and 15% achieve remission after 6 weeks of treatment 6
Important Limitations and Caveats
- Ketamine lacks long-term efficacy and safety trials in major depressive disorder 1
- The VA/DoD Clinical Practice Guideline is the only major guideline that addresses ketamine use for depression 1
- Patients should be informed about potential adverse effects including dissociative symptoms, hypertension, and confusion/agitation 8, 4
- In individuals with a history of chronic ketamine use, there have been reports of genitourinary pain that may necessitate cessation of treatment 3
- Consider discontinuing ketamine if genitourinary pain continues in the setting of other genitourinary symptoms 3