Matthew J. Friedman

Pharmacotherapy for PTSD

Since each us has previously published reviews of medication treat ment for adults and children with posttraumatic stress disorder (PTSD),[1 ] we approach the subject somewhat differently in this arti cle. We ask and answer 11 questions that we believe encompass major con cerns of prescribing psychiatrists about medication treatment for adults or children with PTSD. We hope that this presentation provides a syn thesis of research literature in a form that directly addresses common clinical decisions.

Considering future pharmacotherapy for PTSD.

Posttraumatic stress disorder (PTSD) is a prevalent, disabling, and often chronic condition that may develop following exposure to a traumatic event. Despite the immense social and economic ramifications of PTSD, there has been relatively little recent development of new pharmacotherapies. The majority of pharmacological randomized clinical trials (RCTs) that has been conducted are now dated. Existing treatments for PTSD primarily have come out of research that tested medications developed for other disorders such as antidepressants, anti-hypertensives, antipsychotics, anticonvulsants, and anxiolytics. With an improved understanding of the complex pathophysiology of PTSD, we consider why it has taken so long to identify important targets to advance the field by addressing the underlying pathophysiology in pharmacological interventions. Exciting developments include research into PTSD-related abnormalities associated with dysregulation of adrenergic, hypothalamic-pituitary-adrenocortical, monoaminergic, peptide, glutamatergic, GABAergic, cannabinoid, opioid, and other neurotransmitter and neuroendocrine systems. Yet, this is a broad list and there are many unanswered questions. Current research on biomarkers associated with different clinical phenotypes of PTSD should lead to novel and more specific pharmacotherapeutic strategies. In this brief review, we consider key questions regarding current knowledge on pharmacological treatments for PTSD and highlight evolving practices in future research.

Vermont: A Case History for Supporting National Guard Troops and Their Families

Laurie B. Slone, PhD, and Matthew H. Friedman, MD, PhD, are with the National Center for Posttraumatic Stress Disorder (PTSD), U.S. Department of Veterans Affairs; and the Department of Psychiatry, Dartmouth Medical School. Andrew S. Pomerantz, MD, is with VA Medical Center, White River Junction, Vermont; and the Department of Psychiatry, Dartmouth Medical School. Address correspondence to: Laurie Slone, PhD, 215 N. Main Street, 116-D, VA Medical Center, White River Junction, VT 05009; fax 802-2955135; or e-mail Laurie.Slone@dartmouth.edu. Dr. Slone and Dr. Pomerantz have disclosed no relevant financial relationships. Dr. Friedman has disclosed the following relevant financial relationship: AstraZeneca: Member of Speakers’ Bureau. Laurie B. Slone, PhD; Andrew S. Pomerantz, MD; and Matthew J. Friedman, MD, PhD

Pharmacological management of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) has been conceptualized as an inability to cope with overwhelming stress that is followed by a distinctive pattern of symptoms. This concept has made it possible to develop therapeutic approaches for PTSD that include medication and psychotherapy options. In this article we summarize research studies on pharmacotherapies for PTSD and review new findings in the neurobiology of PTSD that are promoting the development of targeted treatment options. Research findings that have improved our understanding of psychobiological abnormalities associated with PTSD offer clinicians improved treatment strategies. We review those findings, the developments in the medication management of PTSD and common co-occurring disorders, and new areas of pharmacological research on PTSD treatment.

VA’s National PTSD Brain Bank: a National Resource for Research

The National PTSD Brain Bank (NPBB) is a brain tissue biorepository established to support research on the causes, progression, and treatment of PTSD. It is a six-part consortium led by VA’s National Center for PTSD with participating sites at VA medical centers in Boston, MA; Durham, NC; Miami, FL; West Haven, CT; and White River Junction, VT along with the Uniformed Services University of Health Sciences. It is also well integrated with VA’s Boston-based brain banks that focus on Alzheimer’s disease, ALS, chronic traumatic encephalopathy, and other neurological disorders. This article describes the organization and operations of NPBB with specific attention to: tissue acquisition, tissue processing, diagnostic assessment, maintenance of a confidential data biorepository, adherence to ethical standards, governance, accomplishments to date, and future challenges. Established in 2014, NPBB has already acquired and distributed brain tissue to support research on how PTSD affects brain structure and function.

The Role of Obesity in the Association Between Posttraumatic Stress Disorder and Incident Diabetes

Importance Posttraumatic stress disorder (PTSD) is associated with an increased risk of type 2 diabetes mellitus (T2DM). Existing literature has adjusted for obesity in combination with other confounders, which does not allow estimating the contribution of obesity alone on the association of PTSD with incident T2DM. Objective The current study was designed to determine if obesity accounted for the association between PTSD and incident T2DM. Design, Setting, and Participants This cohort study used data from Veterans Health Administration medical records collected from patients with PTSD and without PTSD from 2008 to 2015. Patients were eligible for study inclusion if they were free of prevalent PTSD and T2DM for 12 months prior to index date. To estimate whether the association of PTSD and incident T2DM remained independent of obesity, Cox proportional hazard models were computed before and after adding obesity to the model and then further expanded by adding psychiatric disorders, psychotropic medications, physical conditions, smoking status, and demographics. Additional Cox models were computed to compare the risk of incident T2DM in patients with PTSD with and without obesity. Data analysis was completed from February 2018 to May 2018. Exposures Two International Classification of Diseases, Ninth Revision (ICD-9) codes for PTSD in the same 12 months and obesity, defined by a body mass index of 30 or more or an ICD-9 code for obesity. Main Outcomes and Measures Incident T2DM, as defined by ICD-9 codes. Results Among 2204 patients without PTSD, the mean (SD) age was 47.7 (14.3) years; 1860 (84.4%) were men, 1426 (64.7%) were white, and 956 (43.4%) were married. Among 3450 patients with PTSD, the mean (SD) age was 42.8 (14.2) years; 2983 (86.5%) were men, 2238 (64.9%) were white, and 1525 (44.2%) were married. The age-adjusted association between PTSD and incident T2DM was significant (hazard ratio [HR], 1.33 [95% CI, 1.08-1.64]; P = .01), and after adding obesity to the model, this association was reduced and no longer significant (HR, 1.16 [95% CI, 0.94-1.43]; P = .18). Results of the full model, which included additional covariate adjustment, revealed no association between PTSD and incident T2DM (HR, 0.84 [95% CI, 0.64-1.10]; P = .19). Among patients with PTSD with obesity, the age-adjusted incidence of T2DM was 21.0 per 1000 person-years vs 5.8 per 1000 person-years in patients without obesity. In patients without PTSD, it was 21.2 per 1000 person-years for patients with obesity vs 6.4 per 1000 person-years in those without obesity. Conclusions and Relevance In this study of patients who use the Veterans Health Administration for health care, obesity moderated the association between PTSD and incident T2DM. The incidence of T2DM in patients with PTSD who are not obese is similar to the national incidence rate in the United States. These results suggest PTSD is not likely to have a causal association with incident T2DM. Future research is needed to determine if PTSD remission can lead to weight loss and reduced T2DM incidence.

How and why does the pharmaceutical management of PTSD differ between men and women

Women have typically been found to develop posttraumatic stress disorder (PTSD) at twice the incidence and prevalence rates as men [1]. One explanation for this difference is that women endure more sexual and physical abuse, types of trauma that contribute to increased rates of various psychiatric disorders including PTSD and depression [1]. Yet, the trauma type difference may only partially account for the disparity in PTSD risk as genetic factors may also contribute to increased vulnerability to the development of PTSD [2]. Women are more likely than men to seek mental health services and prefer to get treatment in primary-care clinics [3]. Men, however, are more likely to receive what is considered an ‘adequate dose’ of mental health treatment compared to women [3]. It is possible that gender-related differences in cooccurring disorders may contribute to a difference in provider specialty. Primary-care physicians may be more willing to treat women with PTSD with antidepressant pharmacotherapy, especially when they also present with insomnia, depressive, or anxiety symptoms. On the other hand, primary-care physicians may be more likely to refer men, than women, to mental health specialists, because they present more often with co-occurring substance use disorders (SUD). Such a referral may be more likely to result in psychotherapy, an option increasingly seen as the most effective treatment recommendation for PTSD [4]. Women are more likely than men to be prescribed psychotropic medications overall [5], a difference in medication management that is neither unique to the United States nor limited to a diagnosis of PTSD. Results from a psychotropic drug utilization study of six European countries found that women receive anxiolytics at significantly higher rates than men [6]. Women veterans with PTSD are more likely to receive psychotropic medications across all drug classes (including those not recommended to be used such as benzodiazepines), with the single exception of prazosin, an agent recommended for trauma-related nightmares [5]. In this editorial, we offer an overview of how gender differences have been noted in PTSD pharmacotherapy practice and discuss special considerations regarding treatment of women with PTSD. We share an expert opinion on why an improved sociocultural and neurobiological understanding of gender differences in PTSD may inform the field and help to address treatment recommendations for women. It is critically important to offer clinical guidance on PTSD treatment recommendations for women that take factors such as pregnancy and co-occurring disorders into account.