LAUSR

There is an urgent need to address a critical lack of advancement in the psychopharmacologic treatment of posttraumatic stress disorder (PTSD). The clinical, social, and financial burden of ineffectively treated PTSD is enormous (1–6). The impact of PTSD morbidity and mortality is further magnified by its substantial disruptions in family, workplace, and societal contexts (7). For the Department of Veterans Affairs (VA) and Department of Defense (DoD), i.e., institutions that are vehicles for the expression of the national debt to military personnel who developed PTSD as a consequence of their military service, the need to help these people has taken on significant priority. One in 10 VA healthcare users have the diagnosis of PTSD, which includes one in four treatment-seeking veterans of the recent wars in Iraq and Afghanistan (8). The prevalence of PTSD in the general population for lifetime is approximately 8% (8) and just under 4% for the current year, making it the fifth most prevalent mental disorder in the United States (9–11). Despite this high prevalence and costly impact, there seems to be no visible horizon for advancements in medications that treat symptoms or enhance outcomes in persons with a diagnosis of PTSD. The nature of this PTSD pharmacotherapy crisis is threefold. First, there are only two medications currently approved for the treatment of PTSD by the U.S. Food and Drug Administration (FDA), sertraline (Zoloft) and paroxetine (Paxil). These medications are helpful but are believed to work via the same mechanism of action (12), and both produce reduction in symptom severity rather than remission of PTSD symptoms (13,14). This efficacy gap may be particularly great for patients treated in VA settings (13). Second, the limited efficacy of the FDA-approved treatments for PTSD has necessitated polypharmacy for the vast majority of patients treated. These offlabel medications, as monotherapy or in combination with other medications, have not been studied adequately for the treatment of PTSD. Therefore, most patients are treated with medications or combinations for which there is little empirical guidance regarding benefits and risks. Third, research and development of new medications for the treatment of PTSD has stalled and there is a void in new drug development. There has not been a medication approved for the treatment of PTSD since 2001, despite the significant need. In a survey of ClinicalTrials.gov, there were few pharmaceutical industrysponsored clinical trials for PTSD that have enrolled patients since 2006: one Phase III clinical trial, four Phase II clinical trials, and no Phase I clinical trials (see The Limited Research Portfolio, below). There is no doubt that there is a deficient pipeline of new PTSD medications and it is uncertain about how to best identify new targets for medication development. Even if there were a more robust investment in PTSD research, questions would remain regarding the optimal design for these studies. The past decade of investments from VA and other