Skip main navigation
Close Drawer MenuOpen Drawer Menu

The American Psychiatric Association (APA) has updated its Privacy Policy and Terms of Use, including with new information specifically addressed to individuals in the European Economic Area. As described in the Privacy Policy and Terms of Use, this website utilizes cookies, including for the purpose of offering an optimal online experience and services tailored to your preferences.

Please read the entire Privacy Policy and Terms of Use. By closing this message, browsing this website, continuing the navigation, or otherwise continuing to use the APA's websites, you confirm that you understand and accept the terms of the Privacy Policy and Terms of Use, including the utilization of cookies.

×
Back to table of contents
Letters to the EditorFull Access

Esketamine and the Need for a New Type of Registry for Drugs With Abuse Potential

Published Online:1 Nov 2019https://doi.org/10.1176/appi.ajp.2019.19060631

To the Editor: Schatzberg (1) and others (2) are right to urge caution in the adoption of esketamine for treatment-resistant depression, but not only because of any effect on opiate pharmacology. The real risk lies in the reliance induced by rapid symptom relief followed by rapid relapse and in how this effect may intersect with socioeconomic status.

Low income independently predicts poor response to repeated ketamine infusions (3), and partial responders tend to take esketamine more frequently and at shorter intervals than those who remit (4). Patients with low income may therefore be at greater risk of developing the tolerance that is warned of in the esketamine nasal spray data sheet (5). Low ability to pay, or other restrictions to access, may also increase switching to cheaper or illegal alternatives.

By asking about previous ketamine use, as well as logging each esketamine treatment, the current esketamine nasal spray registry (6) can assess switching from ketamine to esketamine. However, it crucially fails to track the more likely switch from esketamine to medically administered ketamine, or to illegal ketamine. In the United Kingdom, we are advocating for the introduction of a single digital registry platform for collecting data on all new drugs with abuse potential. This includes esketamine, medically prescribed ketamine, and unwise, but potentially numerically dominant, self-treatment with nonprescribed ketamine.

Postmarketing drug registries are well suited for examining longer-term effects of newly licensed products. However, patterns of switching from one drug with abuse potential to another cannot, self-evidently, be assessed in a registry that collects data about only one product. Collecting data on patients defined by their disease (e.g., treatment-resistant depression) would fail to capture information about those taking the drug off label. The problem requires a new class of “multiproduct” registries that can include off-label use and generic medications as well as new entrants. There is a pipeline of rapidly acting antidepressants in development, some of which have abuse potential, so stakeholders cannot afford to put decisions about the funding models for such registries into the “too difficult” basket.

Department of Psychiatry, University of Oxford, and Oxford Health NHS Foundation Trust, Oxford, U.K. (McShane); Department of Psychiatry and Pharmacology, University of Southampton, Southampton, U.K. (Baldwin); Department of Neurodegenerative, Cerebrovascular, and Psychiatric Disorders, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K. (McAllister-Williams); Maudsley Hospital (Taylor), Department of Neuroimaging (Stone), and Department of Psychological Medicine (Young), Institute of Psychiatry, Psychology, and Neuroscience, King’s College London and South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, London; Department of Behavioral Science and Health, Institute of Epidemiology and Health Care, University College London, London (Winstock).
Send correspondence to Dr. McShane ().

Dr. McShane has served on advisory boards for Eleusis, Janssen, and Sage and has received speaker fees from the American Center for Psychiatry and Neurology–United Arab Emirates. Dr. Baldwin has received speaker fees from Janssen. Dr. McAllister-Williams has received fees from the American Center for Psychiatry and Neurology–United Arab Emirates, the British Association for Psychopharmacology, the European College of Neuropsychopharmacology, the International Society for Affective Disorders, Janssen, LivaNova, Lundbeck, myTomorrows, OCM Communications, Pfizer, the Qatar International Mental Health Conference, Sunovion, Syntropharma, the U.K. Medical Research Council, and Wiley; he has received grant support from the National Institute for Health Research’s Efficacy and Mechanism Evaluation Panel and Health Technology Assessment Panel; and he has received nonfinancial support from COMPASS Pathways. Dr. Taylor has received research funding or consultancy honoraria from Allergan, Galen, Janssen, Lundbeck, Otsuka, and Sunovion. Dr. Winstock is the founder and CEO of Global Drug Survey, an independent research organization that conducts research on drug issues, including the therapeutic potential of psychedelics. Dr. Young has served as a consultant to the South London and Maudsley NHS Foundation Trust; he has served on the speakers bureau and/or advisory boards for and/or as a consultant to Allergan, Bionomics, Compass, Janssen, Johnson & Johnson, LivaNova, Lundbeck, and Sunovion; and he has received research funding and/or grant support from Compass, Janssen, LivaNova, Lundbeck, the Medical Research Council, and the National Institute for Health Research. Dr. Stone reports no financial relationships with commercial interests.

References

1 Schatzberg AF: A word to the wise about intranasal esketamine. Am J Psychiatry 2019; 176:422–424Link, Google Scholar

2 Freedman R, Brown AS, Cannon TD, et al.: Can a framework be established for the safe use of ketamine? (editorial). Am J Psychiatry 2018; 175:587–589Link, Google Scholar

3 Zheng W, Zhou YL, Liu WJ, et al.: Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression. J Psychiatr Res 2018; 106:61–68Crossref, Medline, Google Scholar

4 Janssen Research and Development: Advisory committee briefing document: esketamine nasal spray for patients with treatment-resistant depression, Table 21. 2019 (https://www.fda.gov/media/121377/download)Google Scholar

5 Spravato (package insert). Beerse, Belgium, Janssen Research and Development, 2019 (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf)Google Scholar

6 Spravato Risk Evaluation and Mitigation Strategy Patient Monitoring Form, 2019 (https://www.spravatorems.com/pdfs/SPRAVATO(TM)_REMS_Patient_Monitoring_Form.pdf)Google Scholar