Is ketamine effective and safe for treatment-resistant depression?

Summary

Single-dose intravenous ketamine shows a significant improvement in depression scores within 1 to 3 days compared to placebo, with an odds ratio of 11-13. Additionally, twice- or thrice-weekly IV ketamine can improve symptoms by 20%-25% over two weeks. Augmenting sertraline with oral ketamine moderately improves symptoms for six weeks. However, ketamine therapy can cause side effects like confusion and dizziness, and nasal esketamine may lead to severe dizziness and elevated blood pressure in some patients.

Study at a glance

Abstract

MAYBE, but it's too soon to tell. There is limited evidence that ketamine by itself is effective in the very short term. Single-dose intravenous (IV) ketamine is more likely than placebo (odds ratio = 11-13) to produce improvement (> 50%) in standardized depression scores in 1 to 3 days, lasting up to a week. Twice- or thriceweekly IV ketamine improves symptom scores by 20%-25% over 2 weeks (strength of recommendation [SOR]: B, meta-analysis of small, low-quality, randomized controlled trials [RCTs] and a single small RCT).Augmentation of sertraline with daily oral ketamine moderately improves symptom scores for 6 weeks in patients with moderate depression (SOR: B, small, lowquality RCTs).Augmentation of oral antidepressants (duloxetine, escitalopram, sertraline, venlafaxine) with intranasal esketamine spray improves response and remission rates at 4 weeks (16% for both outcomes) in patients with predominantly treatment-resistant major depression (SOR: A, meta-analysis of RCTs).Ketamine therapy is associated with confusion, emotional blunting, headache, dizziness, and blurred vision (SOR: A, metaanalyses).Nasal esketamine spray produces the adverse effects of dizziness, vertigo, and blurred vision severe enough to cause discontinuation in 4% of patients; it also can produce transient elevation of blood pressure (SOR: A, meta-analyses).