Demographic and clinical predictors of response and remission in the treatment of major depressive disorder with ketamine and esketamine: A systematic review.

Psychiatry research  – March 01, 2025

Source: PubMed

Summary

Breakthrough treatments ketamine and esketamine show promise in treating major depressive disorder, helping patients who haven't responded to traditional therapies. A comprehensive analysis of 44 studies reveals that certain traits—including sleep problems, memory function, and metabolic health—may influence treatment success. While patient characteristics like age and gender don't significantly impact outcomes, those with specific symptoms like anhedonia may respond particularly well.

Abstract

Accumulating evidence supports the efficacy of (es)ketamine in the treatment of major depressive disorder (MDD), particularly treatment-resistant depression (TRD). Yet around 50% of the individuals with TRD do not respond to (es)ketamine. Elucidating predictors of response and remission could improve treatment outcomes at the individual level by defining subpopulations that are most likely to benefit from (es)ketamine. This systematic review outlines the predictive value of demographic and clinical characteristics for treatment outcomes of (es)ketamine in MDD. A systematic literature search was performed to retrieve studies investigating the association between baseline characteristics and the likelihood of achieving response and remission following (es)ketamine treatment in MDD. Forty-four studies investigating the association between response and remission and demographic variables, characteristics of the depressive episode, treatment resistance, psychiatric comorbidities, symptomatology, suicidal risk/attempts, family/personal history, medication use, somatic variables, personality traits, and neurocognitive performance were included. The predictive value of demographic and clinical variables for treatment outcomes of (es)ketamine was limited with either no significant relationship or inconsistent results. Findings provide preliminary support for a positive association of response with anhedonia, sleep disturbances, childhood physical abuse, obesity, openness, better episodic memory, and visual learning, poorer neurocognitive performance, slower processing speed, and lower attention, as well as a negative association with melancholic depression, benzodiazepine use, and metabolic syndrome. However, these characteristics have been investigated in a limited number of studies and warrant replication. These findings suggest that (es)ketamine represents a promising treatment prospect for individuals who present clinical characteristics that are often considered difficult to treat.

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