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

A. Philipp-Muller, Taras Reshetukha, Gustavo Vazquez, Roumen Milev, D. Armstrong, Jasleen Jagayat, Nazanin Alavi

JMIR Research Protocols May 11, 2021 DOI: 10.2196/30334 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial (open-label, waitlist-controlled; study protocol) Peer reviewed
Sample size 20
Population Patients with refractory posttraumatic stress disorder recruited from a community clinic
Intervention Ketamine
Dose subanesthetic intravenous ketamine
Duration 14 weeks
Topics Esketamine Ketamine PTSD
Registration NCT04771767
Key findings The protocol proposes that combining subanesthetic intravenous ketamine with therapist-administered internet-based cognitive behavioral therapy will reduce PTSD symptoms more than a waitlist control over 14 weeks, with an expected large effect size (η2=0.14). The authors contend this is the first study to assess e-CBT combined with ketamine for refractory PTSD.

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://clinicaltrials.gov/ct2/show/NCT04771767. International Registered Report Identifier (IRRID) PRR1-10.2196/30334

Comparable studies

Other randomized controlled trials on ketamine for PTSD, most cited first.

Study Year Design Participants
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures 2014 Randomized controlled trial n = 41
A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Individuals with chronic PTSD 2021 Randomized controlled trial n = 30
Long term structural and functional neural changes following a single infusion of Ketamine in PTSD Individuals diagnosed with PTSD 2023 Randomized controlled pilot trial n = 27
d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study. Patients with post-traumatic stress disorder (PTSD) 2018 Pilot randomized placebo-controlled study n = 20
Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol. Veterans with PTSD 2024 Randomized controlled trial n = 100

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