What is the efficacy of daily ketamine for treating depression and anxiety?

From the Guidelines

Daily ketamine is not recommended for depression and anxiety treatment due to the increased risk of serious side effects and the potential for tolerance development and addiction. Ketamine therapy typically involves intermittent dosing, usually 2-3 times per week initially, then tapering to once weekly or biweekly maintenance sessions, as supported by the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline 1. For depression and anxiety, ketamine is generally administered at doses of 0.5-1.0 mg/kg intravenously over 40 minutes, or via intranasal esketamine (Spravato) at 56-84 mg under medical supervision.

Key Considerations

• The antidepressant effects of ketamine typically last 3-7 days after a single dose, making spaced treatments more appropriate, as shown in a meta-analysis of 20 RCTs evaluating the efficacy of single-dose ketamine in different subgroups 1.
• Daily use significantly increases the risk of serious side effects including bladder damage (ketamine cystitis), cognitive impairment, tolerance development, and potential addiction.
• Ketamine works by blocking NMDA receptors and increasing BDNF (brain-derived neurotrophic factor), which promotes neuroplasticity, and this mechanism doesn't require daily dosing to maintain effectiveness.

Treatment Approach

If considering ketamine treatment, patients should work with a psychiatrist experienced in ketamine therapy to develop an appropriate treatment schedule that balances efficacy with safety concerns. Current evidence suggests that both ketamine infusion and intranasal esketamine improve depressive symptoms in patients with MDD for whom at least 2 previous adequate trials of antidepressant medications have failed 1.

Safety and Efficacy

The 2022 guideline recommends ketamine or esketamine as a treatment option in patients who have not responded to several adequate pharmacologic trials, highlighting the importance of careful patient selection and monitoring 1. By prioritizing intermittent dosing and careful patient monitoring, healthcare providers can minimize the risks associated with ketamine treatment while maximizing its potential benefits for patients with depression and anxiety.

From the Research

Efficacy of Daily Ketamine for Treating Depression and Anxiety

• The efficacy of daily ketamine for treating depression and anxiety has been studied in various research papers 2, 3, 4, 5, 6.
• Ketamine has been shown to be a safe and effective alternative to standard depression treatment, with studies demonstrating its ability to provide rapid and robust antidepressant effects within hours of administration 2, 4.
• A retrospective controlled analysis found that patients treated with ketamine intravenous therapy (KIT) exhibited significant and concordant reduction in both anxiety and depression symptoms after induction, with minimal increases in symptoms during maintenance up to a year post-induction 3.
• Ketamine has also been found to be effective in treating anxiety disorders, with a review of the literature presenting case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders 5.
• However, the safety and efficacy of ketamine in patients with psychotic depression has not been established, and further research is needed to determine its long-term safety and tolerability 6.

Key Findings

• Ketamine has been shown to be effective in reducing symptoms of depression and anxiety in patients who do not respond to conventional pharmacologic medications 2, 3.
• The use of ketamine in real-world care settings has been found to be effective in reducing symptoms of depression and anxiety, with significant and concordant reduction in symptoms after induction and minimal increases in symptoms during maintenance 3.
• Ketamine has a unique mechanism of action, rapid onset, and high rate of response, making it a promising treatment option for refractory anxiety disorders 5.
• However, the effects of long-term use of ketamine are unknown, and further research is needed to determine its long-term safety and tolerability 5, 6.

Study Limitations

• The retrospective nature of some studies limits the interpretation of the data, with incomplete patient information and sample attrition being major limitations 3.
• The safety and efficacy of ketamine in patients with psychotic depression has not been established, and further research is needed to determine its long-term safety and tolerability 6.