Add-on esketamine may work against treatment-resistant depression

Treatment with esketamine as an add-on to antidepressants shows modest efficacy in adults with treatment-resistant depression, reports a study. Its effect on suicidality, however, is not significant.

A team of investigators searched the database of Medline with ‘esketamine’ as the keyword on 24 March 2024 using the PRISMA method. They then carried out data processing and statistical analysis with R, version 4.3.3, and conducted the meta-analysis with the METAFOR package.

In total, 1,115 articles were initially identified, of which 87 were included in the analysis and discussion.

Randomized controlled trials reported mostly “negative” or “failed” results at week 2 to 4. However, the meta-analysis revealed a weak but significant positive effect of esketamine on depression (effect size range, 0.15–0.23 at weeks 2 to 4), which was comparable to augmentation strategies with atypical antipsychotics for treatment-resistant depression.

Notably, the effect size regarding suicidality was not significant at any time point. Similar results were obtained from the sensitivity analysis.

“These findings need to be considered in light of esketamine’s abuse potential and the fact that long-term effects are still not fully known,” the investigators said. 

“Some alarming signs concerning deaths and emerging suicidality during the testing phase are discussed, along with other regulatory issues,” they added.

Intranasal esketamine is an adjunctive therapy that has been approved for use among individuals with treatment-resistant major depressive disorder with acute suicidal ideation and behaviour, according to the investigators.