General Anesthetics to Treat Major Depressive Disorder: Clinical Relevance and Underlying Mechanisms

Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases. Clinical observations over the past few decades appear to confirm this possibility. Indeed, equipotency of general anesthesia alone in comparison with electroconvulsive therapy under general anesthesia has been demonstrated in several clinical trials. Importantly, in the past 15 years, intravenous administration of subanesthetic doses of ketamine have also been demonstrated to have rapid antidepressant effects. The molecular, cellular, and network mechanisms underlying these therapeutic effects have been partially identified. Although several important questions remain to be addressed, the ensemble of these experimental and clinical observations opens new therapeutic possibilities in the treatment of depressive disorders. Importantly, they also suggest a new therapeutic role for anesthetics that goes beyond their principal use in the perioperative period to facilitate surgery. Accepted for publication September 19, 2017. Funding: None. The author declares no conflicts of interest. Reprints will not be available from the author. Address correspondence to Laszlo Vutskits, MD, PhD, Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, 4, rue Gabrielle-Perret-Gentil, 1211 Geneva 4, Switzerland. Address e-mail to laszlo.vutskits@unige.ch. © 2017 International Anesthesia Research Society

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