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Letter to the Editor

Dr Lund and Colleagues Reply

Brian C. Lund, PharmD, MS; Nancy C. Bernardy, PhD; Bruce Alexander, PharmD; and Matthew J. Friedman, MD, PhD

Published: August 15, 2013

See original letter by Steenen et al

Dr Lund and Colleagues Reply

To the Editor: We thank Mr Steenen and colleagues for their thoughtful comments concerning our examination of benzodiazepine prescribing trends among veterans with posttraumatic stress disorder (PTSD).1 We agree that the breadth of effective treatment options for PTSD is woefully sparse and that the evidence base supporting any individual treatment is less than optimal.

Mr Steenen and colleagues describe a set of preclinical animal studies examining the effect of systemic midazolam administration on reconsolidation memory. It is unknown at this time whether this intriguing line of scientific inquiry will ultimately lead to a clinically effective human treatment for PTSD, either to prevent the development of PTSD following traumatic exposure or to reduce symptom burden among individuals with existing PTSD. However, it is unclear how the animal studies described could be used to support guideline-discordant benzodiazepine prescribing for veterans with PTSD. The animal protocols involve one-time benzodiazepine administration, rather than the chronic daily treatment observed in our work. In addition, there are alternative agents under investigation, such as propranolol and hydrocortisone, which may achieve the same effect on memory reconsolidation with a less imposing risk profile.2,3 We are not in a position to speak for the Management of Post-Traumatic Stress Working Group, which is responsible for the recommendations contained in the PTSD clinical practice guideline.4 However, if new clinically relevant evidence emerged supporting the effectiveness of benzodiazepines in this population, we feel confident that the PTSD clinical practice guidelines would be updated to reflect that practice.

We join with Mr Steenen and colleagues in expressing the need for additional research seeking effective PTSD treatments and the hope that promising preclinical models may ultimately translate into useful human therapies.

References

1. Lund BC, Bernardy NC, Alexander BA, et al. Declining benzodiazepine use in veterans with posttraumatic stress disorder. J Clin Psychiatry. 2012;73(3):292-296. PubMed doi:10.4088/JCP.10m06775

2. Poundja J, Sanche S, Tremblay J, et al. Trauma reactivation under the influence of propranolol: an examination of clinical predictors. Eur J Psychotraumatol. 2012;3:15470. PubMed doi:10.3402/ejpt.v3i0.15470

3. Zohar J, Yahalom H, Kozlovsky N, et al. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies. Eur Neuropsychopharmacol. 2011;21(11):796-809. PubMed doi:10.1016/j.euroneuro.2011.06.001

4. Department of Veterans Affairs, Department of Defense. Clinical practice guideline for management of post-traumatic stress: version 2.0-2010. http://www.healthquality.va.gov/ptsd/cpg_PTSD-FULL-201011612.pdf. Updated October 2010. Accessed January 24, 2013.

Brian C. Lund, PharmD, MS

[email protected]

Nancy C. Bernardy, PhD

Bruce Alexander, PharmD

Matthew J. Friedman, MD, PhD

Author affiliations: Center for Comprehensive Access and Delivery Research and Evaluation (Dr Lund) and Pharmacy Service (Dr Alexander), Iowa City VA Health Care System, Iowa City, Iowa; and National Center for PTSD, Veterans Affairs Medical Center, White River Junction, Vermont (Drs Bernardy and Friedman).

Potential conflicts of interest: Dr Alexander is a stock shareholder in Exact Sciences. Drs Lund, Bernardy, and Friedman report no potential conflicts of interest relevant to the subject of this letter.

Funding/support: None reported.

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