Oral ketamine for depression: An updated systematic review

Area of Science:

• Pharmacology
• Neuroscience
• Psychiatry

Background:

• Ketamine, a glutamate N-methyl-D-aspartate receptor antagonist, is explored for major depressive disorder treatment.
• Oral ketamine presents advantages in accessibility and scalability over intravenous formulations.
• This review assesses oral ketamine, esketamine, and r-ketamine for unipolar and bipolar depression.

Approach:

• Systematic review of electronic databases from inception to September 2022.
• Inclusion of 22 studies: 4 RCTs, 1 case series, 6 case reports, 5 open-label trials, 6 retrospective chart reviews.
• Analysis of 2336 patients with depression receiving ketamine treatment.

Key Points:

• All included studies reported significant depressive symptom improvement with ketamine.
• Ketamine was generally well-tolerated with no serious adverse events reported.
• Ketamine dosages ranged from 0.5 to 1.25 mg/kg, with administration frequency from daily to monthly.

Conclusions:

• Preliminary evidence supports the antidepressant potential of oral ketamine.
• High risk of bias noted in RCTs due to analysis and adverse event monitoring.
• Further large-scale, long-term studies are required to establish antisuicidal effects and efficacy in treatment-resistant depression.