What is the subanesthetic dose of ketamine for treatment of depression?

From the Guidelines

The recommended subanesthetic dose of ketamine for treating depression is typically 0.5 mg/kg administered intravenously over 40 minutes, as supported by recent clinical guidelines 1. This dose is significantly lower than the doses used for anesthesia (1-4.5 mg/kg IV). The treatment regimen usually consists of a series of infusions, often 2-3 sessions per week for 2-3 weeks, followed by maintenance treatments as needed based on symptom recurrence. Some clinics may use alternative protocols with doses ranging from 0.25-1.0 mg/kg. Key points to consider when administering ketamine for depression include:

• Monitoring patients for vital signs and potential side effects, which may include dissociation, dizziness, nausea, and transient blood pressure elevation
• These effects typically resolve within 1-2 hours after infusion
• Ketamine at subanesthetic doses works differently than at anesthetic doses, primarily by blocking NMDA receptors and increasing BDNF (brain-derived neurotrophic factor), which promotes neuroplasticity and may help restore neural connections impaired in depression
• This mechanism allows for rapid antidepressant effects, often within hours to days, unlike traditional antidepressants which may take weeks to work As noted in the 2022 clinical practice guideline for the management of major depressive disorder, ketamine infusions can be an effective adjunctive treatment for short-term reduction in suicidal ideation in patients with suicidal ideation and MDD 1.

From the Research

Subanesthetic Dose of Ketamine for Treatment of Depression

• The subanesthetic dose of ketamine for the treatment of depression is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg 2.
• A single dose of 0.5 mg/kg of ketamine infused intravenously over 40 minutes, or a single intranasal dose of esketamine, can cause rapid antidepressant and antisuicidal effects within hours of administration, and the antidepressant effect may last up to a week 3.
• The antidepressant effect of subanesthetic doses of ketamine is currently considered to be predominantly mediated by improved neuroplasticity in cortico-limbic areas in the brain 3.
• Ketamine is currently viable as a treatment option for treatment-resistant depression (TRD) that offers the possibility of rapid symptom improvement, with esketamine receiving FDA approval as an adjunctive treatment for TRD in adults 4.
• The use of subanesthetic dose of ketamine administered before each electroconvulsive therapy session can improve antidepressant and sleep quality outcomes in patients with major depressive disorder 5.

Administration and Dosage

• Ketamine can be administered through various routes, including intravenous, intranasal, oral, sublingual, transmucosal, intramuscular, and subcutaneous routes 2.
• The ketamine dose is conventionally administered across 40 minutes, but safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration 2.
• Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously 2.

Efficacy and Safety

• The results of studies on the use of ketamine for depression have shown that it can be an effective treatment option, with rapid antidepressant and antisuicidal effects 3, 4.
• However, the use of ketamine is not without risks, and side effects can include dissociative symptoms, hypertension, and confusion/agitation, although these appear to be tolerable and limited to around the time of treatment 4.
• Further longitudinal studies are warranted to determine the safety and efficacy of repeated administration of ketamine and its analogs to prevent relapse and recurrence of depression 3, 4.