Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation

Summary & key facts

This article reviews studies on ketamine and esketamine for adults with treatment-resistant major depression. The authors say these drugs are the first non-monoamine treatments that can work quickly, but there are remaining questions about safety, long-term effects, and how best to use them in real-world care. The paper summarizes the evidence on how well they work, their tolerability, and gives practical guidance and priorities for future research.

Key facts:

• Many people with major depressive disorder do not reach full symptom or functional recovery with standard monoamine antidepressants, even after multiple treatments.
• Ketamine and esketamine are described as the first non-monoaminergic medicines shown to have rapid-onset antidepressant effects in adults with treatment-resistant depression.
• Despite evidence of rapid benefit, the authors note ongoing concerns about the safety and tolerability of ketamine and esketamine in mood disorders.
• There is uncertainty about where ketamine and esketamine should sit in treatment plans, how they compare with each other or other options, and what clinical setting, infrastructure, and trained personnel are needed for safe use.
• The article is a synthesis of the literature and provides practical guidance for clinicians at the point of care, and it highlights areas where experts agree and where more research is needed.

Abstract

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.

Topics

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Adverse effect Depression (economics) Economics Intensive care medicine Internal medicine Ketamine Macroeconomics Major depressive disorder Medicine Monoaminergic Mood Pharmacology Psychiatry Psychology Receptor Serotonin Tolerability Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood