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Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation

Jules S Mitchell, Daniel Francis Hermens, Maxwell R. Bennett, Adem T. Can, Jim Lagopoulos

CNS Drugs January 22, 2023 DOI: 10.1007/s40263-022-00984-4 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Narrative review Peer reviewed
Interventions Zinc supplementation Ketamine
Dose sub-anaesthetic doses of ketamine, low-dose ketamine
Topics Esketamine Ketamine
Citations 15
Key findings The authors argue that anorexia nervosa is associated with NMDA receptor-mediated excitatory and inhibitory neurometabolite dysfunction, supported by region-specific magnetic resonance spectroscopy findings linked to psychopathology. They propose that zinc supplementation and sub-anaesthetic ketamine may help normalise this dysfunction, and that combined low-dose ketamine plus zinc warrants future investigation to extend therapeutic benefits, with biological markers outlined for assessing and potentially predicting treatment response.

Abstract

Anorexia nervosa is a disorder associated with serious adverse health outcomes, for which there is currently considerable treatment ineffectiveness. Characterised by restrictive eating behaviours, distorted body image perceptions and excessive physical activity, there is growing recognition anorexia nervosa is associated with underlying dysfunction in excitatory and inhibitory neurometabolite metabolism and signalling. This narrative review critically explores the role of N-methyl-D-aspartate receptor-mediated excitatory and inhibitory neurometabolite dysfunction in anorexia nervosa and its associated biomarkers. The existing magnetic resonance spectroscopy literature in anorexia nervosa is reviewed and we outline the brain region-specific neurometabolite changes that have been reported and their connection to anorexia nervosa psychopathology. Considering the proposed role of dysfunctional neurotransmission in anorexia nervosa, the potential utility of zinc supplementation and sub-anaesthetic doses of ketamine in normalising this is discussed with reference to previous research in anorexia nervosa and other neuropsychiatric conditions. The rationale for future research to investigate the combined use of low-dose ketamine and zinc supplementation to potentially extend the therapeutic benefits in anorexia nervosa is subsequently explored and promising biological markers for assessing and potentially predicting treatment response are outlined.

Comparable studies

Other narrative reviews on ketamine, most cited first.

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