Strategies to mitigate dissociative and psychotomimetic effects of ketamine in the treatment of major depressive episodes: a narrative review
Matthew N. Cooper, Joshua D. Rosenblat, Danielle S. Cha, Yena Lee, Ron Kakar, Roger S McIntyre
The World Journal of Biological Psychiatry January 11, 2016 DOI: 10.3109/15622975.2016.1139747 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | Psychotomimetic Dissociative Antidepressant Pharmacology Adverse effect Mood Nmda receptor |
| Citations | 40 |
| Key findings | Intranasal administration appears the most promising strategy to mitigate dissociative and psychotomimetic effects associated with ketamine, but studies are limited in number and quality. |
Abstract
Objectives: Replicated evidence has demonstrated that ketamine exerts rapid-acting and potent antidepressant effects. Notwithstanding, its promise to mitigate depressive symptoms and suicidality in antidepressant-resistant populations, several limitations and safety concerns accompany ketamine including, but not limited to, the potential for abuse and psychotomimetic/dissociative experiences. The focus of the current narrative review is to synthesise available evidence of strategies that may mitigate and fully prevent treatment-emergent psychotomimetic and dissociative effects associated with ketamine administration.
Methods: PubMed, Google Scholar and ClinicalTrials.gov were searched for relevant articles.
Results: Potential avenues investigated to minimise psychotomimetic effects associated with ketamine administration include the following: (1) altering dosing and infusion rates; (2) route of administration; (3) enantiomer choice; (4) co-administration with mood stabilisers of antipsychotics; and (5) use of alternative N-methyl-d-aspartate (NMDA)-modulating agents. Emerging evidence indicates that dissociative experiences can be significantly mitigated by using an intranasal route of administration, lower dosages, or use of alternative NMDA-modulating agents, namely lanicemine (AZD6765) and GLYX-13.
Conclusions: Currently, intranasal administration presents as the most promising strategy to mitigate dissociative and psychotomimetic effects; however, studies of strategies to mitigate the adverse events of ketamine are limited in number and quality and thus further investigation is still needed.