Summary

This small, randomized double-blind crossover trial found that a single infusion of ketamine, compared with psychoactive placebo, was associated with rapid reduction in PTSD symptoms in patients with chronic PTSD. As in previous studies, the effects of ketamine were short-lived, and side effects included transient dissociative symptoms and hemodynamic instability in some patients.

Design

• Randomized, double-blind, crossover trial.
• N=41 patients with chronic PTSD, ages 18-55, randomized to receive a single 40-minute IV infusion of:
  • Ketamine 0.5 mg/kg
  • Midazolam 0.045 mg/kg
• Participants were 46% female, average age 36, mean duration of PTSD 13 years.
• As this was a crossover study, participants received the alternate drug (ketamine or midazolam) 2 weeks after the first infusion if they scored ≥50 on the Clinician-Administered PTSD Scale (CAPS).
• Midazolam (short-acting benzodiazepine) was used as the control condition due to its similarities with ketamine (fast onset of action, short half-life, sedation, and disorientation), to enhance study blinding.
• Patients were instructed to remain free of concomitant psychotropic medications, alcohol, or substances of abuse throughout the trial.
• Setting: Icahn School of Medicine at Mount Sinai, from 2009-2012.
• Primary outcome: change in PTSD symptom severity at 24 hours, assessed by the Impact of Event Scale-Revised (IES-R).
• Secondary outcomes (at 24 hours, 48 hours 72 hours, 7 days after infusion):
  • Montgomery-Asberg Depression Rating Scale (MADRS)
  • Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR)
  • Clinical Global Impression–Severity (CGI-S) and –Improvement (GCI-I) scales

Results

• In crossover analysis, ketamine was associated with significantly improved IES-R score at 24 hours compared with midazolam, with a mean difference of 12.7 points (95% CI, 2.5-22.8, P=0.02). Similar effects were seen in IES-R subscales (intrusion, avoidance, hyperarousal), as well as CGI-S and CGI-I scales at 24 hours.
• Mean CAPS score at day 7 did not reach significance.
• Depression symptoms: MADRS score was significantly more improved with ketamine than with midazolam at 24 hours.
• Adverse Events: Dissociative and hemodynamic adverse effects were associated with ketamine, but not psychotic or manic symptoms. Three patients were treated with beta-blockers for acute hypertension following infusion of ketamine. Blurred vision was common with ketamine.

Reference

Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71(6):681-688. doi:10.1001/jamapsychiatry.2014.62.