Abstract
Objective: To examine whether benzodiazepine use within 30 days after mass trauma increases posttraumatic stress disorder (PTSD) risk and whether timing or persistence of use modifies this association.
Methods: This retrospective cohort study leveraged 3 advantages: large-scale clinical dataset (∼4 million individuals), unprecedented collective exposure to trauma, and novel methodological approach addressing severity bias. Using data from Clalit Health Services (covering ∼54% of the population), we identified 15,570 benzodiazepine-naïve adults who received a new benzodiazepine prescription within 30 days of index date (October 7, 2023). Medication exposure was defined by prescription redemption (none, early ≤7 days, late 8–30 days) and by persistence based on refill behavior. Incident PTSD diagnoses (ICD-10 F43.1) were identified over 12 months. Cox proportional hazards models estimated hazard ratios (HRs), adjusting for demographic characteristics and psychiatric history.
Results: Overall PTSD incidence was 5.0% (773/15,570). Twelve-month risk was 5.2% for nonpurchasers, 4.7% for early purchasers, and 5.0% for late purchasers. Fully adjusted models showed no increased risk with early (HR=0.98, 95% CI=0.80–1.20) or late (HR=1.11, 95% CI=0.94–1.31) purchase. Persistent users had elevated risk (HR=1.60, 95% CI=1.14–2.25 and HR=2.07, 95% CI=1.60–2.68), whereas discontinued users did not. Among Gaza border residents (n=238), both early (HR=0.52, 95% CI=0.31–0.88) and late (HR=0.62, 95% CI=0.38–0.98) purchasers had lower PTSD risk than nonpurchasers.
Conclusions: In this naturalistic setting of mass trauma, short-term benzodiazepine use during 30 days postexposure was not associated with increased 12 month PTSD risk. Among highly trauma-exposed individuals, it was linked to reduced risk at 12 months. These findings challenge current caution against early benzodiazepine use in the immediate aftermath of trauma.
J Clin Psychiatry 2026;87(3):25m16307
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References (22)
- Edinoff AN, Nix CA, Hollier J, et al. Benzodiazepines: uses, dangers, and clinical considerations. Neurol Int. 2021;13(4):594–607. PubMed
- Griffin CE, Kaye AM, Bueno FR, et al. Benzodiazepine pharmacology and central nervous system–mediated effects. Ochsner J. 2013;13(2):214–223. PubMed
- Otto MW, Bruce SE, Deckersbach T. Benzodiazepine use, cognitive impairment, and cognitive-behavioral therapy for anxiety disorders: issues in the treatment of a patient in need. J Clin Psychiatry. 2005;66(Suppl 2):34–38. PubMed
- Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatry. 2015;72(2):136–142. PubMed
- Neria Y, Nandi A, Galea S. Post-traumatic stress disorder following disasters: a systematic review. Psychol Med. 2008;38(4):467–480. PubMed
- Bryant RA. Early intervention for post-traumatic stress disorder. Early Intervention Psychiatry. 2007;1(1):19–26.
- Rahamim O, Segev A, Sinai D. Benzodiazepine prescribing patterns following mass traumatic events. JAMA Psychiatry. 2025 Aug 13;82(11):1133–1136. doi:10.1001/jamapsychiatry.2025.1981. CrossRef
- American Psychological Association. Guideline update panel for the treatment of PTSD in adults. In: APA Clinical Practice Guideline for the Treatment of Posttraumatic Stress Disorder (PTSD) in Adults [Internet]; 2025. Accessed September 22, 2025. Available from. https://www.apa.org/ptsd-guideline/ptsd.pdf
- NICE. Overview Post-traumatic stress disorder Guidance. NICE; 2018. Accessed September 22, 2025. https://www.nice.org.uk/guidance/ng116.
- VA/DoD Clinical Practice Guideline. Management of Posttraumatic Stress Disorder and Acute Stress Disorder Work Group. U.S. Government Printing Office; 2023. Accessed September 22, 2025. https://www.healthquality.va.gov/guidelines/MH/ptsd.
- Campos B, Vinder V, Passos RBF, et al. To BDZ or not to BDZ? That is the question! Is there reliable scientific evidence for or against using benzodiazepines in the aftermath of potentially traumatic events for the prevention of PTSD? A systematic review and meta-analysis. J Psychopharmacol. 2022;36(4):449–459. PubMed CrossRef
- Mellman TA, Bustamante V, David D, et al. Hypnotic medication in the aftermath of trauma. J Clin Psychiatry. 2002;63(12):1183–1184. PubMed
- Sendor R, Stürmer T. Core concepts in pharmacoepidemiology: confounding by indication and the role of active comparators. Pharmacoepidemiol Drug Saf. 2022;31(3):261–269. PubMed
- Katsoty D, Greidinger M, Neria Y, et al. A prediction model of PTSD in the Israeli population in the aftermath of October 7th, 2023, terrorist attack and the Israel–Hamas war. Isr J Health Pol Res. 2024;13(1):1.
- Gelpin E, Bonne O, Peri T, et al. Treatment of recent trauma survivors with benzodiazepines: a prospective study. J Clin Psychiatry. 1996;57(9):390–394. PubMed
- Baranyi A, Krauseneck T, Rothenhäusler HB. Posttraumatic stress symptoms after solid-organ transplantation: preoperative risk factors and the impact on health-related quality of life and life satisfaction. Health Qual Life Outcomes. 2013;11(1):111. PubMed CrossRef
- Bustos SG, Maldonado H, Molina VA. Midazolam disrupts fear memory reconsolidation. Neuroscience. 2006;139(3):831–842. PubMed
- Matar MA, Zohar J, Kaplan Z, et al. Alprazolam treatment immediately after stress exposure interferes with the normal HPA-stress response and increases vulnerability to subsequent stress in an animal model of PTSD. Eur Neuropsychopharmacol. 2009;19(4):283–295. PubMed CrossRef
- Thai TN, Winterstein AG. Core concepts in pharmacoepidemiology: measurement of medication exposure in routinely collected healthcare data for causal inference studies in pharmacoepidemiology. Pharmacoepidemiol Drug Saf. 2024;33(3):e5683. PubMed CrossRef
- Mouthaan J, Sijbrandij M, Reitsma JB, et al. The role of early pharmacotherapy in the development of posttraumatic stress disorder symptoms after traumatic injury: an observational cohort study in consecutive patients. Gen Hosp Psychiatry. 2015;37(3):230–235. PubMed CrossRef
- Clarfield AM, Manor O, Nun GB, et al. Health and health care in Israel: an introduction. Lancet. 2017;389(10088):2503–2513. PubMed
- Rosenqvist TW, Wium-Andersen MK, Wium-Andersen IK, et al. Long-term use of benzodiazepines and benzodiazepine-related drugs: a register-based Danish cohort study on determinants and risk of dose escalation. Am J Psychiatr. 2024;181(3):246–254. PubMed CrossRef
