Letters to the Editor Diffusion of Prazosin Treatment for PTSD To THE EDITOR: We found the article by Dr. Raskind et al. in the September issue of the Journal to be a most convincing demonstration of the broad efficacy of prazosin treatment (1). As suggested by Dr. Friedman in the accompanying editorial (2), this research is likely to foster prazosin's increased use. Accordingly, the drug's growing use for PTSD across the Veterans Health Administration (VHA) merits examination. We compared data from a previous study examining the geographic distribution of prazosin use for PTSD in the VHA between 2004 and 2006 with recent data from 2012 (3). In 2004, 5% of all veterans diagnosed with PTSD in VHA mental health specialty clinics received prazosin, a figure that increased to 17% in 2012. However, in 2004, 38% of patients diagnosed with PTSD within the Puget Sound VA Medical Center, where the treatment was developed, were prescribed prazosin, yvith monotonie declines to only 2% at medical centers 2,500 miles away or farther, including U.S. East Coast centers. By contrast, in 2012,33% of patients with PTSD within Puget Sound were prescribed prazosin, a small decline, while the proportion treated with prazosin at medical centers 2,500 miles away or farther had increased 7.6 times to 15%. Prescriptions Increased 1.4 times at distances of up to 499 mUes, 2.8 times from 500 to 999 miles, and 4.4 times from 1,000 to 2,499 miles. While prazosin use is stül greatest at the facility where the treatment was pioneered, the geographic gradient has decreased. This reduction most likely refiects the progressive research Dr. Eriedman describes and diffusion of these findings into clinical practice, likely bolstered by the 2010 VHA PTSD treatment guidelines, which encouraged this treatment option, including ongoing academic detailing and other active efforts within the VHA (4). Until now, the phenomenon of a large gradient in the geographic use of prazosin has largely been of academic interest. With this new publication, however, this gulf may be transformed from an academic curiosity to a concerning health care disparity, i.e., an inequity in the delivery of mental health services that typically demands increased efforts to encourage use of the therapy. The findings described here highlight shifts in the path by which research drives progress in psychiatric practice from academic publications to guidelines, education, and academic detailing. References 1. Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Homas D, Hill J, Daniels C, Calohan J, Millard SP, Rohde K, O'Connell J, Pritzl D, Feiszli K, Pétrie EC, Gross C, Mayer CL, Freed MC, Engel C, Peskind ER: A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry 2013; 170:10031010 2. Friedman MJ: Toward rational pbarmacotberapy for posttraumatic stress disorder: reprise. Am J Psychiatry 2013; 170: 944-946 3. Harpaz-Rotem I, Rosenheck RA: Tracing the flow of knowledge: geographic variability in the diffusion of prazosin use for the treatment of posttraumatic stress disorder nationally in the Department of Veterans Affairs. Arch Gen Psychiatry 2009; 66: 417-421

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4. VA/DoD Clinical Practice Guideline: Management of Post-Traumatic Stress, version 2.0. Oct 2010 (http://www.healthquality.va.gov/ PTSD-FULL-2010c.pdf) ERIC HERMES, M.D. ILAN HARPAZ-ROTEM, PH.D. ROBERT ROSENHECK, M.D.

From the VA New England Mental Illness Research, Education, and Clinical Center and the VA-Yale Clinical Neurosciences PTSD Research Program, VA Connecticut Health Care System, West Haven, Conn, and the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. Supported by the Department of Veterans Affairs, Veterans Health Affairs, VISN 1 career development award to Dr. Hermes, and the VA New England Mental Illness Research, Education, and Clinical Center. Dr. Rosenheck has received research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, and Wyeth; consulting fees from Bristol-Myers Squibb, Eli Lilly, fanssen, and Roche; and he was a testifying expert in fones ex rel. the State of Texas v. fanssen Pharmaceutica Products. Dr. Hermes and Harpaz-Rotem report no financial relationships with commercial interests. This letter (doi: 10.1176/appi.ajp.2013.13091259) was accepted for publication in November 2013.

High Dosages of Antidepressants Prescribed Without Risk? To THE EDrroR: In the June issue of the Journal, Zivin et al. (1) examined whether high-dosage citalopram or sertraline would increase the risk of ventricular arrhythmia or mortality. Their study, tapping a large database, found decreased risk associated yvith high-dosage antidepressants, contradicting Eood and Drug Administration (EDA) warnings of greater risk of QT interval prolongation and torsade de pointes with highdosage citalopram. Several issues regarding that study warrant attention. When physicians' choice of antidepressant dosage is affected by risk of poor prognosis, confounding by indication may occur (2) and lead to results suggesting that high dosages of antidepressants are safe. Even before the EDA warning, low dosages of antidepressants were commonly prescribed for frail or elderly patients, who are more likely to develop adverse outcomes. Thus, the decreased or absent risk associated with a high-dosage prescription may result from a fauure to consider various important unmeasured confounders (e.g., increased cardiac output) and mediators (e.g., smoking cessation) in a healthier study population. This bias can worsen when a measurement of person-time is used, because combining the number of persons and the duration of their time in the study may increase the diversity of interactions, allowing the impact of omitted variables to become more pervasive in regression analysis. Taken together, if the risk for different dosage groups is not assessed with equipoise, the results cannot substitute for results obtained from the crossover study submitted to the EDA.

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