Efficacy and Tolerability of Two Novel “Standard of Care” Treatments—Intranasal Esketamine Versus Intravenous Ketamine—for Treatment-Resistant Depression in Naturalistic Clinical Practice: Protocol for a Pilot Observational Study
Gilmar Gutierrez, Joshua D. Rosenblat, Emily R. Hawken, Jennifer Swainson, Gustavo Vazquez
JMIR Research Protocols May 1, 2022 DOI: 10.2196/34711 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational pilot study (multicenter prospective observational protocol) Qualitative Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Adults with moderate to severe unipolar treatment-resistant depression who are candidates for low-dose IV ketamine or intranasal esketamine as part of standard care |
| Interventions | Ketamine Esketamine |
| Measures | Montgomery and Åsberg Depression Rating Scale, Clinician Administered Dissociative Symptom Scale (CADSS-6), Likeability and Craving Questionnaire |
| Topics | Depression Esketamine Ketamine |
| Key findings | The authors hypothesize that intravenous ketamine and intranasal esketamine will produce comparable rapid and robust antidepressant effects with similar tolerability profiles in real-world treatment of resistant depression. The protocol aims to compare effectiveness, tolerability, dissociation, and abuse potential, and to provide expert commentary on clinical application. |
Abstract
Background: Intravenous (IV) ketamine and intranasal (IN) esketamine have been studied as novel alternatives to manage treatment-resistant depression (TRD). The objective of this observational pilot study is to compare the real-world effectiveness and tolerability of IV ketamine and IN esketamine in the management of unipolar TRD.
Objective: To compare the effectiveness (primary outcome measure) and tolerability (secondary outcome measure) of racemic ketamine and esketamine in the management of TRD in adults and provide an expert qualitative commentary on the application of IV ketamine and IN esketamine in clinical practice (exploratory objective), focusing on the recruitment process, patient retention, effectiveness, and tolerability of the treatments.
Methods: This is a multicenter prospective observational study of naturalistic clinical practice. We expect to recruit 10 patients per treatment arm—IV ketamine or IN esketamine per center (2 centers, total 40 subjects). Patients experiencing moderate to severe TRD and who are candidates for receiving low-dose IV ketamine treatments or IN esketamine as part of their standard-of-care treatments will be recruited. We will measure the effectiveness of each treatment arm by measuring the severity of depression symptoms using the Montgomery and Åsberg Depression Rating Scale; tolerability, side effects, and the appearance of dissociation symptoms using the simplified 6-item version of the Clinician Administered Dissociative Symptom Scale (CADSS-6); and potential for abuse using a Likeability and Craving Questionnaire. Logistic regression will examine odds ratios, number needed to treat for response and remission, number needed to harm, and likelihood to be helped or harmed of each treatment. Covariate analysis will assess the impact of site and demographic variables on treatment efficacy.
Results: This observational trial was approved by the Queen’s University Health Science and Affiliated Teaching Hospital’s Research Ethics Board in February 2021. The two research centers involved have started patient recruitment. Our research center (Providence Care Hospital, Kingston, Ontario) has recruited 9 patients so far. We expect to finalize data gathering by August 2022. The manuscript is expected to be published by December 2022.
Conclusions: We hypothesize that both treatments will have comparable rapid and robust antidepressant effects and similar tolerability profiles in a real-world setting for the management of TRD. International Registered Report Identifier (IRRID) DERR1-10.2196/34711
Comparable studies
Other non-randomized and open-label trials on esketamine for depression, most cited first.