Promises and Pitfalls of NMDA Receptor Antagonists in Treating Violent Aggression.
Caitlyn J Bartsch, Jacob C. Nordman
Frontiers in Behavioral Neuroscience June 21, 2022 DOI: 10.3389/fnbeh.2022.938044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Interventions | Ketamine Memantine |
| Topics | Ketamine Neuroplasticity |
| Keywords | Nmda receptor Memantine Aggression Medial amygdala Early life stress |
| Key points | The authors propose that ketamine and memantine oppositely affect aggression brought on by early life stress, substance abuse, or attack experience through opposite effects on NMDAR-dependent synaptic plasticity, which could explain their persistent effects and make them a longer-lasting treatment option. They caution that effects depend on prior drug use, traumatic stress, or aggressive history, and call for more cellular and synaptic research and thorough medical and psychiatric evaluation before responsible administration. |
Abstract
Treatment options for chronically aggressive individuals remain limited despite recent medical advances. Traditional pharmacological agents used to treat aggression, such as atypical antipsychotics, have limited efficacy and are often replete with dangerous side effects. The non-competitive NMDAR antagonists ketamine and memantine are promising alternatives, but their effects appear to be highly dependent on dosage, context, and personal experience. Importantly, these drugs can increase aggression when combined with substances of abuse or during periods of heightened stress. This is likely due to mechanistic differences operating at specific synapses under different contexts. Previous findings from our lab and others have shown that early life stress, substance abuse, and attack experience promote aggression through NMDAR-dependent synaptic plasticity within aggression-related brain circuits. Ketamine and memantine affect these types of aggression in opposite ways. This has led us to propose that ketamine and memantine oppositely affect aggression brought on by early life stress, substance abuse, or attack experience through opposite effects on NMDAR-dependent synaptic plasticity. This would account for the persistent effects of these drugs on aggression and suggest they could be leveraged as a more long-lasting treatment option. However, a more thorough examination of the effects of ketamine and memantine on cellular and synaptic function will be necessary for responsible administration. Additionally, because the effects of ketamine and memantine are highly dependent on prior drug use, traumatic stress, or a history of aggressive behavior, we propose a more thorough medical evaluation and psychiatric assessment will be necessary to avoid possible adverse interactions with these drugs.
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| Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy | 2021 | Theoretical or philosophical paper | |
| Therapeutic mechanisms of psychedelics and entactogens. | 2023 | Theoretical or philosophical paper |
Citations in the library
Cites 25
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- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine Anesthesia & Analgesia November 1, 1998
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
and 20 more in the library