Combining Ketamine and Internet-Based Cognitive Behavioral Therapy for the Treatment of Posttraumatic Stress Disorder: Protocol for a Randomized Controlled Trial

Aaron Emile Philipp-Muller, Taras Reshetukha, Gustavo Vazquez, Roumen Milev, Dawn Armstrong, Jasleen Jagayat, Nazanin Alavi, Aaron Emile Philipp-Muller, Taras Reshetukha, Gustavo Vazquez, Roumen Milev, Dawn Armstrong, Jasleen Jagayat, Nazanin Alavi

Abstract

Background: Over one third of patients with posttraumatic stress disorder (PTSD) do not respond to current interventions. Ketamine presents a potential treatment option; however, its effects are temporary. Administering ketamine alongside psychotherapy is one potential means of prolonging its effects; however, only a few studies have investigated this treatment method to date, and none have tested ketamine with internet-based or electronically delivered cognitive behavioral therapy (e-CBT).

Objective: This open-label randomized controlled trial aims to assess the efficacy of a combined treatment method of subanesthetic intravenous ketamine and e-CBT for treating patients with PTSD.

Methods: In total, 20 patients with refractory PTSD recruited from a community clinic will be randomly assigned to either an experimental group (n=10), receiving a combination of ketamine and therapist-administered e-CBT over 14 weeks, or a waitlist control group (n=10), receiving the experimental treatment after 14 weeks. Both groups will be assessed for the symptoms of PTSD and comorbid disorders before treatment, at two midway points, and at the end of the experiment.

Results: PTSD symptoms of participants in the experimental group are expected to improve significantly more than those of participants in the waitlist control group (P=.05) with a large effect size (η2=0.14).

Conclusions: This is the first study to assess the relationship between e-CBT and ketamine and their combined ability to treat refractory PTSD. If successful, this study will open web-based, asynchronous therapeutic options for patients with PTSD and will provide new insights into the functional role of glutamate in trauma-related disorders as well as in learning, memory, and fear extinction.

Trial registration: ClinicalTrials.gov NCT04771767; https://ichgcp.net/clinical-trials-registry/NCT04771767.

International registered report identifier (irrid): PRR1-10.2196/30334.

Keywords: PTSD; cognitive behavioral therapy; electronic; internet; ketamine; mental health; mental health care; online; psychotherapy; virtual.

Conflict of interest statement

Conflicts of Interest: NA is Assistant Professor of Psychiatry at Queen’s University and has cofounded OPTT, the care delivery platform in use, and has ownership stakes in OPTT Inc. RM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, the Canadian Institutes of Health Research, Janssen, Lallemand, Lundbeck, Nubiyota, the Ontario Brain Institute, and the Ontario Mental Health Foundation.

©Aaron Emile Philipp-Muller, Taras Reshetukha, Gustavo Vazquez, Roumen Milev, Dawn Armstrong, Jasleen Jagayat, Nazanin Alavi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 20.07.2021.

Figures

Figure 1
Figure 1
Summary of the experimental design and time course. This study will follow a 25- to 39-week period, including an 8-week period of stable treatment before recruitment, 3 weeks of screening, 14 weeks of experimental treatment or waitlist treatment, and 14 weeks of postexperiment treatment for patients in the waitlist condition. eCBT: electronically delivered cognitive behavioral therapy; PTSD: posttraumatic stress disorder.
Figure 2
Figure 2
Web-based intervention example material.

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