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

• Published in: Psychiatry research 2025-03, Vol.345, p.116355, Article 116355
• Main Authors: Lima Constantino, Juliana, Godschalk, Martijn, van Dalfsen, Jens H., Veraart, Jolien K.E., Spijker, Jan, van Exel, Eric, Schoevers, Robert A., Kamphuis, Jeanine
• Format: Article
• Language: English
• Subjects: Esketamine; Ketamine; Major depressive disorder; Systematic review; Treatment-resistant depression
• ISSN: 0165-1781; 1872-7123; 1872-7123
• DOI: 10.1016/j.psychres.2025.116355

•Predictive value of demographic and clinical variables for (es)ketamine is limited.•Positive response linked to anhedonia, sleep issues, obesity, openness, and others.•Negative response linked to melancholic depression, benzodiazepine use, and others.•Research warranted on early change variables and utilizing data-driven techniques. 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.