Ketamine and its chemical derivative, esketamine, have the ability to alleviate severe depression almost instantly, particularly in cases resistant to other treatments. This represents a significant breakthrough in psychiatry.
However, a complex mix of economic, regulatory, and research barriers have resulted in these potentially life-saving treatments remaining out of reach for many patients with severe depression.
Drawing inspiration from a recent editorial in the Australian & New Zealand Journal of Psychiatry that I co-authored with colleagues at The George Institute for Global Health, this article explores the complexities of racemic ketamine’s stalled journey from promising research to patient care. It highlights disparities in the drug development and approval process that favour patented medications despite their higher costs and not necessarily superior effectiveness. It also explores multifaceted strategies that could pave the way for the development of affordable treatments.
Editor’s Note: for a refresher on racemic ketamine and its enantiomers, see our Racing Beyond Racemic feature from November 2022.
Depression stands as one of the most pervasive health challenges of our time. It is widespread, affecting an estimated 280 million people worldwide – roughly 1 in every 20 people – and is one of the leading causes of disability. Amidst this challenge, ketamine has emerged as a breakthrough antidepressant.
First synthesized in 1962, ketamine is primarily recognised as an anesthetic. However, in the 2000’s, the groundbreaking discovery that ketamine-induced potent and rapid antidepressant effects (Berman et al., 2000) altered the course of psychiatry.
Ketamine’s unique capability to rapidly relieve symptoms, often within hours, established it as the first rapid-acting antidepressant. Moreover, the fact that these antidepressant effects could last for about a week and occurred in individuals who were treatment-resistant underscored a significant breakthrough. Ketamine’s effects mark the first novel approach to treating depression in over fifty years and set a precedent for mental health treatments that are both fast-acting and relatively long-lasting.
For over two decades, numerous studies have consistently confirmed these early findings, demonstrating ketamine’s efficacy in treating severe, treatment-resistant depression. However, progress towards making ketamine widely accessible has been slow. Its classification as a generic drug makes it less appealing for pharmaceutical industry investment. As a result, ketamine research has largely depended on public funding, which has led to primarily small-scale studies (Figure 1 and 2). Without the financial backing of an industry sponsor to support larger, definitive trials, racemic ketamine has been unable to obtain the regulatory approval needed for its widespread use among public healthcare systems, and its reimbursement by both public and private payors.