Ketamine and its Regulatory Implications: A Review

Ketamine, an NMDA receptor antagonist approved as an anesthetic since 1970, is increasingly used off-label at subanesthetic doses for depression and other conditions, despite risks of dissociative, psychomimetic, and hemodynamic symptoms. The rise of largely unregulated ketamine clinics, sometimes using compounded formulations, poses patient safety concerns. The article reviews ketamine's pharmacology and evidence for off-label use, and suggests regulatory measures for clinics, compounding pharmacies, and providers.

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Abstract

ABSTRACT: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been approved for use as a clinical and veterinary anesthetic since 1970. Although esketamine, a specific molecular form of ketamine, is FDA-approved for the management of treatment-resistant depression, regular ketamine is often used off-label at subanesthetic doses to treat depression as well as other psychiatric disorders and pain. Despite the lower doses of ketamine used for analgesia and depression, ketamine can cause dissociative, psychomimetic, and hemodynamic symptoms that require careful monitoring during and after administration. Over the past several years, rising public interest in ketamine has led to a “wild west” of so-called ketamine clinics, which offer off-label ketamine treatment, sometimes through compounding pharmacies, for a variety of conditions. These clinics are largely unregulated, representing a possible ongoing threat to the safety of patients which may merit action among state medical regulators. Regulations may be helpful for all of the stakeholders in the off-label ketamine marketplace, including distributors, compounding pharmacies, clinics, and providers themselves. In this article, the pharmacology of ketamine and evidence supporting off-label use are reviewed, along with suggestions for regulating the burgeoning ketamine clinic landscape.