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The interactive effects of ketamine and magnesium upon depressive-like pathology

Shawn P. Hayley, Sara Razmjou, Darcy Litteljohn, Chris Rudyk, Shuaib Seyed, Melanie Clarke, Rowan Pentz, Zachary Dwyer

Neuropsychiatric Disease and Treatment September 1, 2016 DOI: 10.2147/ndt.s111131 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical animal study Peer reviewed
Population Animals (rodents) used in the forced swim test
Interventions Ketamine Magnesium hydroaspartate
Dose 15 mg/kg ketamine
Measures forced swim test
Topics Esketamine Ketamine
Citations 6
Key points A single 15 mg/kg dose of ketamine induced rapid antidepressant-like effects in the forced swim test but did not affect brain levels of brain-derived neurotrophic factor. Contrary to the authors' hypothesis, magnesium administration or a magnesium-deficient diet did not influence ketamine's effects on these outcomes, so the data do not support magnesium as an adjunct agent.

Abstract

Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration. However, it is also a drug with an abusive potential and can have marked side effects. Hence, this study aimed at enhancing the antidepressant-like effects of ketamine (allowing for lower dosing regimens) by coadministering magnesium hydroaspartate (Mg(2+) normally affects the same receptors as ketamine) and also assessed whether an Mg(2+)-deficient diet would modify the impact of ketamine. It was found that a single 15 mg/kg dose of ketamine did indeed induce rapid antidepressant-like effects in the forced swim test but did not affect brain levels of the brain-derived neurotrophic factor. Contrary to our hypothesis, magnesium administration or deficiency did not influence the impact of ketamine on these outcomes. Thus, these data do not support the use of magnesium as an adjunct agent and instead suggest that further research involving other antidepressant and animal models is required to confirm the present findings.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study Year Design Participants
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats 2010 Observational study
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats 1997 Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice 2016 Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats 1983 Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice 2015 Experimental study

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Esketamine Ketamine Depression Neuroplasticity