Rothbaum, B. O., & Watkins, L. E. (2025).
American Journal of Psychiatry, 182(5), 424–437.
Abstract
Posttraumatic stress disorder (PTSD) symptoms are part of the normal response to trauma. Most trauma survivors will recover over time without intervention, but a significant minority will develop chronic PTSD, which is unlikely to remit without intervention. Currently, only two medications, sertraline and paroxetine, are approved by the U.S. Food and Drug Administration to treat PTSD, and the combination of brexpiprazole and sertraline and MDMA-assisted therapy have FDA applications pending. These medications, and the combination of pharmacotherapy and psychotherapy, are not recommended as first-line treatments in any published PTSD treatment guidelines. The only interventions recommended as first-line treatments are trauma-focused psychotherapies; the U.S. Department of Veterans Affairs/Department of Defense PTSD treatment guideline recommends prolonged exposure (PE), cognitive processing therapy (CPT), and eye movement desensitization and reprocessing, and the American Psychological Association PTSD treatment guideline recommends PE, CPT, cognitive therapy, and trauma-focused cognitive-behavioral therapy. Although published clinical trials of psychedelic-assisted psychotherapy have not incorporated evidence-based PTSD psychotherapies, they have achieved greater response rates than other trials of combination treatment, and there is some enthusiasm about combining psychedelic medications with evidence-based psychotherapies. The state-of-the-art PTSD psychotherapies are briefly reviewed here, including their effects on clinical and neurobiological measures.
The article is paywalled, unfortuantely.
Here is a summary and some thoughts.
In the evolving landscape of PTSD treatment, Rothbaum and Watkins reaffirm a crucial truth: trauma-focused psychotherapies remain the first-line, evidence-based interventions for posttraumatic stress disorder (PTSD), outperforming pharmacological approaches in both efficacy and durability.
The State of PTSD Treatment
While most individuals naturally recover from trauma, a significant minority develop chronic PTSD, which typically requires intervention. Current FDA-approved medications for PTSD—sertraline and paroxetine—offer only modest relief, and recent psychedelic-assisted therapy trials, though promising, have not yet integrated evidence-based psychotherapy approaches. As such, expert guidelines consistently recommend trauma-focused psychotherapies as first-line treatments.
Evidence-Based Therapies at the Core
The VA/DoD and APA guidelines converge on recommending prolonged exposure (PE) and cognitive processing therapy (CPT), with eye movement desensitization and reprocessing (EMDR), cognitive therapy, and trauma-focused CBT also strongly supported.
PE helps patients systematically confront trauma memories and triggers to promote extinction learning. Its efficacy is unmatched, with robust support from meta-analyses and neurobiological studies.
CPT targets maladaptive beliefs that develop after trauma, helping patients reframe distorted thoughts through cognitive restructuring.
EMDR, though somewhat controversial, remains a guideline-supported approach and continues to show effectiveness in trials.
Neurobiological Insights
Modern neuroscience supports these therapies: PTSD involves hyperactivation of fear and salience networks (e.g., amygdala) and underactivation of emotion regulation circuits (e.g., prefrontal cortex). Successful treatment—especially exposure-based therapy—enhances extinction learning and improves functional connectivity in these circuits. Moreover, cortisol patterns, genetic markers, and cardiovascular reactivity are emerging as potential predictors of treatment response.
Innovations and Expansions
Therapists are increasingly utilizing massed formats (e.g., daily sessions over 2 weeks), virtual reality exposure therapy, and early interventions in emergency settings. These models show high completion rates and comparable outcomes to traditional weekly formats.
One particularly innovative direction involves MDMA-assisted psychotherapy. Although still investigational, trials show higher remission rates when MDMA is paired with psychotherapy. The METEMP protocol (MDMA-enhanced PE) offers a translational model that integrates the strengths of both approaches.
Addressing Clinical Challenges
High dropout rates (27–50%) remain a concern, largely due to avoidance—a core PTSD symptom. Massed therapy formats have demonstrated improved retention. Additionally, comorbid conditions (e.g., depression, TBI, substance use) generally do not impede response to trauma-focused care and can be concurrently treated using integrated protocols like COPE (Concurrent Treatment of PTSD and Substance Use Disorders Using PE).
Toward Greater Access and Remission
Despite strong evidence, access to high-quality trauma-focused therapy remains limited outside military and VA systems. Telehealth, stepped care models, and broader dissemination of evidence-based practices are key to closing this gap.
Finally, Rothbaum and Watkins argue that remission—not just symptom reduction—must be the treatment goal. With renewed scientific rigor and integrative innovations like MDMA augmentation, the field is inching closer to more effective and enduring treatments.
