Ketamine for Adults With Treatment-Resistant Depression or Post-Traumatic Stress Disorder

Key Messages

• Two randomized controlled trials reported mixed evidence on the efficacy of repeated IV ketamine infusions for improving post-traumatic stress disorder. One randomized controlled trial with small sample size found that repeated IV ketamine infusions significantly improved post-traumatic stress disorder symptoms compared with midazolam in civilian population, while the other randomized controlled trial with larger sample size could not demonstrate a significant efficacy on post-traumatic stress disorder symptoms compared with placebo in military population. The antidepressant effects of ketamine were rapid, but the effects were not sustained after few weeks of post-treatment follow-up.
• One randomized controlled trial comparing IV ketamine with IV esketamine found both treatments had comparable acute antidepressant effects for treatment-resistant depression 24 hours following infusion.
• Two randomized controlled trials provided mixed evidence on the efficacy of single infusion of IV ketamine that was used as anesthetic agent for electroconvulsive therapy for treatment-resistant depression. One randomized controlled trial involving military population showed that patients undergoing electroconvulsive therapy for treatment-resistant depression with ketamine anesthesia had similar improvement of depression when compared with patients undergoing electroconvulsive therapy with methohexital anesthesia. However, in other randomized controlled trial comparing with propofol-based anesthesia in a civilian population, ketamine-based anesthesia provided faster improvement in depressive symptoms and fewer electroconvulsive therapy treatments to achieve disease remission.
• In a small randomized controlled trial, alternate infusions of subanesthetic dose of ketamine or midazolam with alternate electroconvulsive therapy showed no significant difference in antidepressant effects between groups.
• The efficacy of oral ketamine was demonstrated in 1 randomized controlled trial that repeated administration of oral ketamine significantly reduced depressive symptoms compared with placebo.
• A small retrospective chart review study showed that repeated administration of intramuscular ketamine had no significant differences in the improvement of depressive and anxiety symptoms compared with repeated transcranial magnetic stimulation.
• Findings suggest overall safety and tolerability of ketamine for treatment of post-traumatic stress disorder or treatment-resistant depression. Most frequent side effects associated with ketamine were dissociative symptoms and cardiovascular changes such as increased blood pressure and heart rate, but these effects were transient.
• The Danish guideline recommend against the use of IV ketamine in patients with treatment-resistant depression, due to low quality and insufficient evidence regarding the lack of long-term efficacy and the risk of abuse of ketamine. Likewise, the Canadian guideline recommends IV ketamine be considered as third-line treatment for adults with TRD, because of the short-lived efficacy of ketamine, its side effects, and the lack of strategies for relapse prevention after ketamine infusions.