Most trauma survivors recover without intervention, but a minority develop chronic PTSD that requires treatment. Only two medications—sertraline and paroxetine—are FDA-approved for PTSD, with brexpiprazole-sertraline and MDMA-assisted therapy applications pending. Medication and medication-psychotherapy combinations are not recommended as first-line treatments. Instead, trauma-focused psychotherapies—prolonged exposure, cognitive processing therapy, eye movement desensitization and reprocessing, cognitive therapy, and trauma-focused cognitive-behavioral therapy—are the only first-line interventions. Psychedelic-assisted psychotherapy trials have shown higher response rates than other combination treatments, though they have not incorporated evidence-based PTSD psychotherapies. The review covers these state-of-the-art psychotherapies and their clinical and neurobiological effects.
Treatment approaches for posttraumatic stress disorder (PTSD) based on fear conditioning and extinction models are reviewed. Fear extinction provides a translational model linking basic research in nonhuman animals to human treatments such as prolonged exposure therapy. Cognitive aspects of extinction, including consolidation and reconsolidation, are discussed along with behavioral and pharmacological strategies for preventing and treating chronic PTSD. Augmentation strategies reviewed include disrupting noradrenergic processes, NMDA receptor medications, physical exercise, cannabinoids, estradiol, dexamethasone, yohimbine, losartan, dopamine, and MDMA, with evidence for their efficacy in human samples. Limitations and future directions are also addressed.