The Challenges of PTSD Prevention: Placing Benzodiazepine Use in Context

See related article by Rahamim et al

In part based on animal data showing that benzodiazepines can interfere with extinction learning, a process implicated in recovery from trauma,¹ clinical guidelines for the prevention of posttraumatic stress disorder (PTSD) have recommended against the use of benzodiazepines in the aftermath of trauma exposure.^2,3 In line with this, a recent systematic review and meta-analysis⁴ reported that data from cohort studies suggested increased risk for PTSD among trauma-exposed individuals receiving benzodiazepines (risk ratio = 1.53, 95% CI, 1.05–2.23), with a similar trend in data from controlled trials though not statistically significant (standardized mean difference = 0.24, 95% CI, −0.32 to 0.79). However, authors emphasized that the evidence base was limited with only very small sample size prospective trials, methodologically weak, and heterogeneous. In this issue of The Journal of Clinical Psychiatry, using claim data from approximately 4 million individuals in Israel within 30 days of the October 7, 2023, mass trauma exposure to identify over 15,000 benzodiazepine-naïve adults who received a new benzodiazepine prescription, Rahamim et al⁵ elegantly examine timing and persistence of filling benzodiazepine prescriptions with risk for 12-month PTSD diagnosis coded in the medical record, adjusting for multiple potential confounders in initial and sensitivity analyses. In the full sample, the authors reported no association between new PTSD diagnosis coding and filling a benzodiazepine prescription in the first week or later in the first month. Further, among the subsample (n = 238) closest to the Gaza border for whom PTSD rates were nearly 8 times higher (39% vs 5% PTSD in the full sample), increasing likelihood of traumatic exposure, both early and later benzodiazepine use after exposure to mass trauma were associated with lower PTSD risk. They also found, however, that persistent benzodiazepine use (defined as at least 1 prescription refill within a week of first prescription) was associated with elevated risk for PTSD in the full sample. Of note, limitations of this pharmacoepidemiologic approach include lack of knowledge whether or how often those without a refill used the initial prescription—potentially biasing toward the null, as the authors note—or whether formal PTSD diagnostic criteria were met.

While this new study is an important contribution, these mixed results unfortunately do not definitively clarify the role of benzodiazepines in the prevention of PTSD. They do, however, suggest the possibility that at a population level single prescriptions of benzodiazepines may not increase population rates of PTSD after a mass casualty event inclusive of unmeasured variation in use of initial filled prescriptions and levels of confirmed trauma exposure, and that moderating effects may be implicated in the association between benzodiazepine use and later PTSD. In fact, the present findings are consistent with the idea that heterogeneity of populations, trauma types, and prescribing patterns may explain the heterogeneity of results reported across previous cohort studies.⁴

The report by Rahamim et al⁵ also emphasizes that for lack of a better alternative, benzodiazepines were prescribed to alleviate distress in the aftermath of trauma exposure. It is important to note that among the number of acute posttrauma pharmacotherapy PTSD prevention candidates, hydrocortisone is, to date, the only compound that has been associated with a significant reduction in PTSD risk relative to placebo in 2 randomized trials,^6,7 though a recent Cochrane review concluded that the level of evidence was inconclusive.⁸ There is clearly a need for more research to identify optimal pharmacotherapeutic approaches that alleviate acute distress while also reducing risk for PTSD. While benzodiazepines are well established as anxiolytics that may acutely address a number of important symptoms such as insomnia and anxiety in times of severe stress, provisional evidence suggests that hydrocortisone might currently be considered as a leading candidate for early secondary PTSD prevention with pharmacotherapy; this is in need of additional confirmatory research.

The inherent safety risks associated with persistent benzodiazepine use, such as psychological and physiological dependence, and the higher rates of PTSD with persistent use reported here should be thoughtfully considered.^8–10 Specifically regarding persistent benzodiazepine use, the authors highlight that their finding of elevated PTSD is confounded by indication, yet the persistent prescription refill group is also the group most confidently taking the prescribed benzodiazepine regularly (or at all) in the first prescription period, another limitation to definitive conclusions.

While the debate about pharmacologic prevention of PTSD is ongoing, with gaps in the evidence base, current guidelines converge more clearly on one point: in the early aftermath of trauma, the strongest clinical support is for indicated prevention for those who are symptomatic using targeted trauma-focused psychosocial interventions rather than medication.^2,11,12 Across guidelines, early trauma-focused psychological interventions are either recommended or viewed more favorably than pharmacologic options. Data from early trauma-focused interventions have been accumulating, though they are also in need of further study. In a randomized pilot trial, Rothbaum et al¹³ assigned 137 emergency department patients to 3 sessions of modified prolonged exposure initiated a mean of 11.8 hours posttrauma versus assessment only and found significantly lower PTSD symptom severity reactions at 4 and 12 weeks, along with lower depressive symptoms at 4 weeks. This was unfortunately not replicated in a later multiarm randomized trial, though the discrepancy may be explained by many individuals recovering naturally and the fact that participants were not optimally selected for preventive intervention.¹⁴ Here again, moderation is likely central, as beyond establishing the efficacy of a PTSD prevention intervention, it is critical to also determine for whom, at what level of initial risk, and under what trauma conditions this intervention will be efficacious. Universal prevention has also focused more on addressing immediate needs such as safety, situational stabilization, communication, social support, psychoeducation and normalization of emotional responses in the acute aftermath of trauma (eg, Hobfoll et al,¹⁵ Department of Veterans Affairs/Department of Defense²). It is unclear in the current study what psychosocial support and/or PTSD psychoeducation was or was not delivered by the primary care physicians alongside their benzodiazepine prescriptions.

Thus, rather than prompting a premature definitive reappraisal of clinical recommendations for use of benzodiazepines as a preventive strategy for PTSD, data from Rahamim et al⁵ reinforce the need for better early risk assessment and stratification when intervening in the aftermath of mass trauma. Female sex has been consistently associated with greater likelihood of PTSD despite lower overall rates of trauma exposure.¹⁶ More broadly, recent umbrella-review evidence indicates that female sex/gender, family psychiatric history, cumulative trauma exposure, and trauma severity are among the better-supported risk factors for PTSD, although prospective evidence remains less conclusive.¹⁷ Earlier work also supports the role of prior trauma exposure, prior psychological adjustment, family psychiatric history, posttrauma social support, and factors operating during or immediately after trauma exposure (ie, peritraumatic reactions).^18,19 Among these, peritraumatic distress appears among the most robust early predictors of later PTSD, including in prospective studies.²⁰ Although all of these variables are imperfect predictors when considered individually, together they might support a more rational stepped-care approach in the early aftermath of trauma.

In conclusion, the present report reminds us of the complexity of early posttrauma pharmacotherapy. The prior benzodiazepine literature was mixed, and this report, while adding important findings to the literature in a well performed, carefully controlled large sample study, nonetheless shares some of the same challenges in this mixed literature, with different findings for initial or repeated prescription refills and inherent limitations of the pharmacoepidemiology design. Current guideline recommendations continue to favor initial focus on immediate safety needs, support, communication, and psychoeducation, followed by early monitoring, with targeted approaches such as trauma-focused psychological interventions for symptomatic high-risk individuals.^2,11,12 In the meantime, routine posttrauma care including in the primary care pathways would likely benefit from systematic screening for known risk factors including marked peritraumatic distress, prior trauma exposure, female sex, and pre-existing psychopathology, followed by rapid referral of those at highest risk toward evidence-based early interventions. Future work should therefore focus on improving early identification of trauma-exposed individuals at risk for PTSD and on determining which patients, based on their initial clinical presentation, trauma context, and care setting, may benefit from specific early psychosocial and/or pharmacologic approaches. Ultimately, more definitive study of available agents and novel targeted treatment approaches that can help address acute distress without increasing PTSD risk after trauma remains needed.

Article Information

Published Online: June 22, 2026. https://doi.org/10.4088/JCP.26com16516
© 2026 Physicians Postgraduate Press, Inc.
J Clin Psychiatry 2026;87(3):26com16516
Submitted: May 11, 2026; accepted May 12, 2026.
To Cite: Bui E, Simon NM. The challenges of PTSD prevention: placing benzodiazepine use in context. J Clin Psychiatry 2026;87(3):26com16516.
Author Affiliations: Department of Psychiatry, Caen University Hospital, Caen, France (Bui); Faculty of Medicine, University of Caen Normandy, Caen, France (Bui); Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (Bui); Department of Psychiatry, NYU Grossman School of Medicine, New York, New York (Simon).
Corresponding Author: Naomi M. Simon, MD, MSc, NYU Grossman School of Medicine, One Park Ave, 8th Floor, New York, NY 10016 ([email protected]).
Financial Disclosures: The authors report no disclosures related to the commentary. In the past 3 years Dr. Simon reports receiving grants from the National Institutes of Health (NIH), Ananda Scientific, American Foundation for Suicide Prevention, Support from Cohen Veterans Network and MindMed and; receiving fees or royalties from Wolters Kluwer (UpToDate) and APA Publishing (Textbook of Anxiety, Trauma and OCD Related Disorders 2020 and APA Grief and Prolonged Grief Disorder 2024). Dr. Bui reports speaking or consulting fees from Johnson & Johnson, licenses or royalties from Springer and Wolters Kluwyer.
Funding/Support: None.