Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Current PTSD treatment guidelines recommend trauma-focused therapies like Prolonged Exposure (PE).
• However, 30-50% of military and veteran patients do not achieve significant symptom improvement with PE alone.
• Ketamine, an NMDA receptor antagonist, shows potential in preclinical studies to enhance fear extinction learning.

Purpose of the Study:

• To compare ketamine combined with PE versus a placebo adjunct to PE for treating PTSD in veterans.
• To assess the efficacy and safety of ketamine-enhanced PE therapy.

Main Methods:

• A single-site randomized controlled trial (RCT) involving 100 veterans with PTSD.
• Participants will receive either ketamine or midazolam (active placebo) infusions prior to PE sessions for 3 weeks.
• Outcomes will be assessed over a 3-month follow-up period, with primary analysis on 80 participants reaching the primary outcome measure.

Main Results:

• Primary outcome measure data not yet available as this is a proposed study.
• Secondary outcomes include depression and anxiety scores, safety, tolerability, and cognitive performance.

Conclusions:

• The study aims to provide a scientific basis for ketamine-enhanced PE therapy in PTSD.
• Findings could refine treatment methodologies, elucidate underlying mechanisms, and identify specific patient subgroups who benefit most.