Is ketamine (Ketamine) effective as a treatment for post-traumatic stress disorder (PTSD)?

Ketamine for PTSD Treatment

Ketamine shows promising efficacy for treating PTSD, with repeated intravenous infusions demonstrating significant symptom reduction compared to placebo in civilian populations, though evidence remains limited and it should not be considered first-line therapy. 1

Efficacy Evidence

The most recent and highest quality evidence comes from a 2021 randomized controlled trial that demonstrated:

• Six infusions of ketamine (0.5 mg/kg) over 2 consecutive weeks produced significantly greater improvement in PTSD symptoms compared to midazolam (placebo) 1
• 67% of participants in the ketamine group were treatment responders, compared with only 20% in the placebo group 1
• The median time to loss of response was 27.5 days following the 2-week course of infusions 1

Earlier research supports these findings:

• A 2014 proof-of-concept study showed that even a single intravenous subanesthetic dose of ketamine (0.5 mg/kg) produced rapid reduction in PTSD symptom severity within 24 hours 2

Important Limitations and Contradictions

Despite promising results, several important limitations exist:

• The American Psychiatric Association and American College of Internal Medicine note "limited evidence for ketamine's use in PTSD" 3
• Population differences matter: while ketamine showed efficacy in predominantly civilian PTSD samples, a study in veteran and military populations did not demonstrate significant PTSD symptom reduction 4
• Most studies have small sample sizes and limited follow-up periods 5, 6
• Functional unblinding remains a concern in ketamine studies due to its dissociative effects 5

Administration Protocol

When considering ketamine for PTSD:

• Dosage: 0.5 mg/kg IV administered over 40 minutes (range 0.1-0.75 mg/kg) 3, 1
• Administration: Should be administered slowly over 60 seconds to avoid respiratory depression 3
• Frequency: Six infusions over 2 consecutive weeks showed the most promising results 1

Monitoring and Side Effects

Careful monitoring is essential:

• Watch for psychotomimetic side effects (dysphoria, nightmares, hallucinations) 3
• Common side effects include dissociative symptoms and nausea 3
• Vital sign monitoring during administration is necessary 3
• Resuscitative equipment should be readily available 3

Contraindications

Ketamine should be avoided in patients with:

• Uncontrolled cardiovascular disease
• Pregnancy
• Active psychosis
• Severe liver dysfunction
• High intracranial or ocular pressure 3
• Use with caution in chronic alcoholics and acutely alcohol-intoxicated patients 3

Clinical Decision Algorithm

1. First consider established PTSD treatments:

   • Trauma-focused psychotherapy
   • FDA-approved medications (sertraline, paroxetine)

2. Consider ketamine when:

   • Patient has failed at least two adequate medication trials
   • Symptoms are severe and disabling
   • Patient is not in an active psychotic state
   • Patient has no contraindications

3. Treatment protocol:

   • Six infusions of ketamine (0.5 mg/kg IV) over 2 consecutive weeks
   • Monitor for response after completion
   • Consider maintenance infusions if initial response is positive

4. Discontinue if:

   • Intolerable side effects develop
   • No meaningful response after completion of protocol
   • Benefits do not outweigh risks

While ketamine shows promise for PTSD treatment, it should be considered an experimental approach that may benefit some patients who have not responded to conventional treatments. The rapid onset of action (within 24 hours) makes it particularly valuable for patients with severe, disabling symptoms requiring urgent intervention 1, 2.