The therapeutic role of ketamine and esketamine in treating psychopathological domains of depression. (1st February 2023)

• Record Type: Journal Article
• Authors: Jawad, Muhammad Youshay; Di Vincenzo, Joshua D.; Badulescu, Sebastian; Teopiz, Kayla M.; Tabassum, Aniqa; Ceban, Felicia; Mckenzie, Andrea; Meshkat, Shakila; Rosenblat, Joshua D.; Ho, Roger C.; McIntyre, Roger S.
• Is Part Of: Neuropharmacology. Volume 223(2023)
• Publication Date: 2023-02-01
• Subjects: Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109299
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Over the past two decades, ketamine has emerged as a novel effective and rapid-acting antidepressant. While the vast majority of studies on ketamine have focused on its ability to reduce the severity of depression broadly, its effectiveness in specific domains such as cognition, anhedonia, suicidality, and workplace/social/scholastic functionality has been neglected. Similarly, current treatments (e.g., SSRIs and SNRIs) aim to improve overall depression severity, which often results in the persistence of one or more residual symptom domains and prevents full recovery to premorbid functionality. In this review, we narratively synthesize the literature pertaining to the effectiveness of ketamine in treating key domains of depressive symptomatology (i.e., cognition, anhedonia, suicidality, and psychosocial functionality). Our findings suggest that ketamine is effective across domains varyingly, with the strongest evidence being for its ability to reduce suicidality. The rapid acting nature of ketamine further supports its use in treating suicidality and potentially preventing the completion of suicide. Evidence for the effectiveness of ketamine in other domains is weak, primarily due to a lack of robust studies specifically designed to assess these domains as primary outcomes. Future studies should scrutinize the effects of ketamine on specific domains of depression to optimize its implementation. This article is part of the Special Issue on 'Ketamine and its Metabolites'. Highlights: Ketamine and its enantiomers are an effective antidepressant modality with varying effectiveness across key domains of depression (i.e., suicidality, psychosocial functionality, cognition and anhedonia). The strongest evidence was shown for reducing suicidality rapidly. The evidence for efficacy of ketamine on ameliorating domains of cognition, psychosocial functioning and anhedonia is weak due to lack of studies mainly studying foregoing domains as primary outcomes. Future researchers should design robust trials to further the therapeutic role of ketamine and its enantiomers in treating disparate domains of depression.