The Long-Term Clinical Outcome of Posttraumatic Stress Disorder With Impaired Coronary Distensibility.

OBJECTIVE: Coronary Distensibility Index (CDI) impairments reflect endothelial-dependent process associated with vulnerable-plaque composition. This study investigated the relation of impaired CDI with posttraumatic stress disorder (PTSD) and their predictive value for major adverse cardiovascular events (MACE). METHODS: This study involved 246 patients (age = 63 [10] years, 12% women) with (n = 50) and without (n = 196) PTSD, who underwent computed tomography angiography to determine coronary artery disease and CDI. Extent of coronary artery disease was defined as normal, nonobstructive (<50% luminal stenosis), and obstructive (>50%). Incidence of MACE, defined as myocardial infarction or cardiovascular death, was documented during a mean follow-up of 50 months. Survival regression was employed to assess the longitudinal association of impaired CDI and PTSD with MACE. RESULTS: A significant inverse correlation between CDI and Clinical Global Impression Severity scale of PTSD symptoms was noted (r = .81, p = .001). CDI was significantly lower in patients with PTSD (3.3 [0.2]) compared with those without PTSD (4.5 [0.3]), a finding that was more robust in women (p < .05). Covariate-adjusted analyses revealed that the relative risk of MACE was higher in patients with PTSD (hazard ratio [HR] = 1.56, 95% CI = 1.34-3.14) and those with impaired CDI (HR = 1.95, 95% CI = 1.27-3.01, per standard deviation lower CDI value). There was also a significant interaction between PTSD and impaired CDI (HR = 3.24, 95% CI = 2.02-5.53). CONCLUSIONS: Impaired CDI is strongly associated with the severity of PTSD symptoms. Both impaired CDI and PTSD were independently associated with an increased risk of MACE during follow-up, and evidence indicated an interaction between these two factors. These findings highlight the important role of CDI in identifying individuals with PTSD at risk for MACE.

Posttraumatic Stress Disorder and Death From Suicide.

PURPOSE OF REVIEW: This review summarizes the increasing public health concern about PTSD and suicide, and the population-based studies that have examined this association. Further, we discuss methodological issues that provide important context for the examination of this association. RECENT FINDINGS: The majority of epidemiologic studies have shown that PTSD is associated with an increased risk of suicide; however, a notable minority of studies have documented a decreased risk of suicide among persons with PTSD. Methodological (e.g., sample size and misclassification) and etiologic issues (e.g., complicated psychiatric comorbidity) may explain the conflicting evidence. PTSD may be associated with an increased risk of suicide, but further research is needed. Increasing the use of appropriate methods (e.g., marginal structural models that can evaluate both confounding and effect modification, machine learning methods, quantification of systematic error) will strengthen the evidence base and advance our understanding.

[Posttraumatic stress disorder : Trigger and consequence of vascular diseases]. / Posttraumatische Belastungsstörung : Auslöser und Folgeerscheinung vaskulärer Erkrankungen.

Posttraumatic stress disorder (PTSD) was previously thought to be a psychological reaction precipitated by exposure to war, sexual and physical violence; however, PTSD is also prevalent after life-threatening medical events, such as stroke and myocardial infarction. After such events PTSD is often underdiagnosed despite the fact that it is clearly associated with adverse clinical outcomes including recurrence of cardiac events and increased mortality. Moreover, PTSD increases the risk of vascular events. This review summarizes the bidirectional relationship between PTSD and vascular diseases and outlines current knowledge regarding clinical features, prevalence and the putative underlying pathophysiological mechanisms.

Cardiovascular Disease Risk Factors in Patients with Posttraumatic Stress Disorder (PTSD): A Narrative Review.

Posttraumatic stress disorder (PTSD) is a chronic condition related to severe stress and trauma. There is a mounting evidence about increased prevalence and mortality from cardiovascular diseases (CVD) in patients with PTSD. This review summarizes the current data on possible relations between PTSD and increased risks of CVD, including biological, psychological and behavioral factors. Biological factors refer to increased prevalence of metabolic syndrome (MetS), hypertension, elevation of pro-inflammatory cytokines and homocysteine levels. Peripheral Brain-derived neurotropic factor (BDNF), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and quantitative electroencephalogram (qEEG) are promising surrogate markers of increased cardiovascular risk. Among psychological factors, some personality traits, such as neuroticism and trait impulsivity/hostility, contribute to the development of PTSD, and are associated with general cardiovascular distress. Recently, type-D (distressed) personality is usually investigated in relation to cardiovascular morbidity, but in populations other than PTSD patients. Behavioral factors refer to unhealthy life-styles, encompassing high smoking rate, drug substances abuse and addiction, physical inactivity and unhealthy diet. The relationships among all these factors are complex and yet incompletely taken into consideration. Because of a high prevalence of CVD in patients with PTSD, there is a strong need for a more intensive focus on this vulnerable population in both primary and secondary cardiovascular prevention as well as in effective treatment possibilities.

Comorbidity Correlates of Death Among New Veterans of Iraq and Afghanistan Deployment.

BACKGROUND: Veterans of the wars in Iraq and Afghanistan who receive care in the Veterans Health Administration (VA) have high disease burden. Distinct comorbidity patterns have been shown to be differentially associated with adverse outcomes, including death. This study determined correlates of 5-year mortality. MATERIALS AND METHODS: VA demographic, military, homelessness, and clinical measures informed this retrospective analysis. Previously constructed comorbidity classifications over 3 years of care were entered into a Cox proportional hazards model of death. RESULTS: There were 164,933 veterans in the cohort, including African Americans (16%), Hispanics (11%), and whites (65%). Most were in their 20s at baseline (60%); 12% were women; 4% had attempted suicide; 4% had been homeless. Having clustered disorders of pain, posttraumatic stress disorder, and traumatic brain injury was associated with death [hazard ratio (HR)=2.0]. Mental disorders including substance abuse were similarly associated (HR=2.1). Prior suicide attempt (HR=2.2) or drug overdose (HR=3.0) considerably increased risk of death over 5 years. CONCLUSIONS: As congressional actions such as Veterans Choice Act offer more avenues to seek care outside of VA, coordination of care, and suicide prevention outreach for recent veterans may require innovative approaches to preserve life.

Predictors and prognostic impact of post-traumatic stress disorder after the great East Japan earthquake in patients with cardiovascular disease.

BACKGROUND: We examined the prevalence, predictors and prognostic impact of post-traumatic stress disorder (PTSD) after the Great East Japan Earthquake in patients with cardiovascular disease (CVD) in the CHART-2 study. METHODS AND RESULTS: The prevalence of PTSD was 14.7% at 6 months after the Earthquake. Female sex, experiencing the Tsunami, property loss, poverty, and insomnia medication use were associated with PTSD. The patients with PTSD more frequently experienced a composite of death, acute myocardial infarction, stroke and heart failure (18.5% vs. 15.0%, P=0.035). CONCLUSIONS: PTSD was frequent in CVD patients after the Earthquake and had an adverse prognostic impact.

Stress and asthma: novel insights on genetic, epigenetic, and immunologic mechanisms.

In the United States the economically disadvantaged and some ethnic minorities are often exposed to chronic psychosocial stressors and disproportionately affected by asthma. Current evidence suggests a causal association between chronic psychosocial stress and asthma or asthma morbidity. Recent findings suggest potential mechanisms underlying this association, including changes in the methylation and expression of genes that regulate behavioral, autonomic, neuroendocrine, and immunologic responses to stress. There is also evidence suggesting the existence of susceptibility genes that predispose chronically stressed youth to both post-traumatic stress disorder and asthma. In this review we critically examine published evidence and suggest future directions for research in this field.

From the neurobiology of extinction to improved clinical treatments.

The neural circuitry underlying the fear response is extremely well conserved across mammalian species, which has allowed for the rapid translation of research findings in rodent models of fear to therapeutic interventions in human populations. Many aspects of exposure-based psychotherapy treatments in humans, which are widely used in the treatment of PTSD, panic disorder, phobias, and other anxiety disorders, are closely paralleled by extinction training in rodent fear conditioning models. Here, we discuss how the neural circuitry of fear learning and extinction in rodent animal models may be used to understand the underlying neural circuitry of fear-related disorders, such as PTSD in humans. We examine the factors that contribute to the pathology and development of PTSD. Next, we will review how fear is measured in animal models using classical Pavlovian fear conditioning paradigms, as well as brain regions such as the amygdala, which are involved in the fear response across species. Finally, we highlight the following three systems involved in the extinction of fear, all of which represent promising avenues for therapeutic interventions in the clinic: (1) the role of the glutamatergic N-methyl-d-aspartate (NMDA) receptor, (2) the role of the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) induced signaling pathway, and (3) the role of the renin-angiotensin system. The modulation of pathways underlying fear learning and extinction, such as the ones presented in this review, in combination with extinction-based exposure therapy, represents promising avenues for therapeutic intervention in the treatment of human fear related disorders.

Posttraumatic stress disorder and cardiometabolic disease.

The need for addressing posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing public health concern. Current PTSD management addresses psychiatric parameters of this condition. However, PTSD is not simply a psychiatric disorder. Traumatic stress increases the risk for inflammation-related somatic diseases and early mortality. The metabolic syndrome reflects the increased health risk associated with combat stress and PTSD. Obesity, dyslipidemia, hypertension, diabetes mellitus, and cardiovascular disease are prevalent among PTSD patients. However, there has been little appreciation for the need to address these somatic PTSD comorbidities. Medical professionals treating this vulnerable population should screen patients for cardiometabolic risk factors and avail themselves of existing preventive diet, exercise, and pharmacologic modalities that will reduce such risk factors and improve overall long-term health outcomes and quality of life. There is the promise that cardiometabolic preventive therapy complementing psychiatric intervention may, in turn, help improve the posttraumatic stress system dysregulation and favorably impact psychiatric and neurologic function. © 2013 S. Karger AG, Basel.

Effect of elective surgery on subjective health in veterans with chronic posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is common, is often chronic, and has been associated with greater risk of postoperative mortality in veterans. The purpose of this study was to determine if elective outpatient surgery had a persistent effect on the physical or mental health of veterans with chronic PTSD. A longitudinal, quasi-experimental study was conducted that followed up 60 veterans with chronic PTSD over 12 weeks. Self-reported physical and mental health, depressive symptom severity, and posttraumatic symptom severity were measured in 29 veterans undergoing outpatient elective surgery and 31 veterans not having elective surgery (controls). Data collection was performed at baseline and repeated 1, 4, and 12 weeks after surgery or enrollment. At baseline, both surgical and control subjects reported poor physical and mental subjective health status. After surgery, surgical group subjects reported mean age- and gender-adjusted reductions of 3.9 points on the Physical Component Summary score and 2.9 points on the Mental Component Summary score of the Veterans Rand 36-item Health Survey, which resolved by 4 weeks after surgery. These findings suggest that veterans with PTSD were at greater risk of mortality because of poor baseline health, but did not demonstrate persistent decline in health following common elective surgical procedures.

The perioperative implications of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a traumatic event and is characterized by symptoms of reexperiencing, emotional numbing, persistent arousal, and avoidance. Approximately 6.8% of the people in the United States will be diagnosed with PTSD at some point in their lives. The presence of PTSD in a surgical patient can be important because PTSD is associated with the use of psychoactive medications, risky health behaviors, cardiovascular comorbidities, depression, chronic pain, and cognitive dysfunction, all of which may influence the risk of perioperative morbidity and mortality. In addition, patients with PTSD are anxious around unfamiliar people and in unfamiliar environments. The purposes of this journal course are to provide anesthetists with a working knowledge of the symptoms, treatments, and comorbidities associated with PTSD and to suggest ways of interacting with patients with the disorder that increase trust and decrease the risk of evoking posttraumatic symptoms in the perioperative environment.

The impact of Purple Heart commendation and PTSD on mortality rates in older veterans.

BACKGROUND: To determine whether having received a Purple Heart (PH) or having been diagnosed with posttraumatic stress disorder (PTSD) affected mortality in older veterans. METHODS: We compared mortality rates of older veterans with a PH but without PTSD (PH+/PTSD-) to veterans with a PH and PTSD (PH+/PTSD+), veterans without a PH but with PTSD (PH-/PTSD+), and a comparison group without a PH or PTSD (PH-/PTSD-). Administrative data from the Veterans Integrated Service Network 16 were collected between 10/01/97 and 09/30/99 for veterans who were 65 years or older. Proportional hazards regression was used to compare the survival times for the four groups (n = 10,255) from entry into the study until death or study termination (9/30/2008). The Charleson co-morbidity index was used to control for potential co-morbid illness burden differences between the groups. RESULTS: Older veterans with a PH (PH+/PTSD- and PH+/PTSD+) had significantly lower mortality rates than PH-/PTSD- veterans (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5 to 0.6, P<.0001; and HR = 0.5, 95% CI 0.4 to 0.7, P<.0001). The PH-/PTSD+ group had a higher mortality rate than the PH-/PTSD- group (HR = 1.1, 95% CI 1.0 to 1.2, P<.01). CONCLUSIONS: Veterans who had PH citations and survived into their seventh decade had half the mortality rate of veterans without PH citations with or without PTSD. Veterans with PTSD but without a PH had a significantly higher mortality rate compared to (PH-/PTSD-). Veterans who suffer combat injury without developing PTSD may provide a useful study population for determining the factors that confer resilience.

War stress and late-life mortality in World War II male civilian resistance veterans.

The mental and physical health of 146 Dutch males exposed to severe war stress during their young adulthood were examined in 1986-1987 when they were at ages 61 to 66 years. The veterans' data were compared with a randomly selected population-based sample of same-aged males. In 2005, 70% of the war stress veterans had died, and only 35% of the comparison group. The baseline quality of life was significantly poorer in the war stress veterans than in the comparison group. Baseline variables explained 42% of the increased risk of mortality among war stress veterans. Smoking was the largest single contributor to mortality.

Concomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database.

3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be important to understand what medications may pose a risk of drug-drug interactions. The goal of this study was to evaluate the risks due to MDMA ingestion alone or in combination with other common medications and drugs of abuse using the FDA drug safety surveillance data. To date, nearly one thousand reports of MDMA use have been reported to the FDA. The majority of these reports include covariates such as co-ingested substances and demographic parameters. Univariate and multivariate logistic regression was employed to uncover the contributing factors to the reported risk of death among MDMA users. Several drug classes (MDMA metabolites or analogs, anesthetics, muscle relaxants, amphetamines and stimulants, benzodiazepines, ethanol, opioids), four antidepressants (bupropion, sertraline, venlafaxine and citalopram) and olanzapine demonstrated increased odds ratios for the reported risk of death. Future drug-drug interaction clinical trials should evaluate if any of the other drug-drug interactions described in our results actually pose a risk of morbidity or mortality in controlled medical settings.

Association of psychiatric illness and all-cause mortality in the National Department of Veterans Affairs Health Care System.

OBJECTIVE: To assess the independent association of seven psychiatric illnesses with all-cause mortality in a representative national sample of veterans, after adjustment for demographic factors, psychiatric and medical comorbidity, obesity, tobacco use, and exercise frequency. METHODS: Analyses were conducted using data from the 1999 Large Health Survey of Veteran Enrollees (n = 559,985). Cox proportional hazards models were used to examine the relationship of seven psychiatric diagnoses with mortality. Date of all-cause mortality was determined from the Department of Veterans Affairs' Beneficiary Identification and Records Locator System. All-cause mortality rates were calculated as the total number of deaths in each group divided by the person-years of follow-up time in each group. RESULTS: During the 9-year study period, 27% of the subjects (n = 131,396) died. Each of the psychiatric diagnoses was associated with significantly increased HR for all-cause mortality after adjusting for age, race, and gender. Hazard ratios ranged from 1.02 (95% confidence interval, 1.01, 1.04) for posttraumatic stress disorder to 1.97 (95% confidence interval, 1.89, 2.04) for alcohol use disorders. After adjustment for psychiatric and medical comorbidity, obesity, current smoking and exercise frequency, alcohol and drug abuse and dependence, and schizophrenia were statistically significantly associated with an increased risk of mortality. CONCLUSIONS: In this study of a large representative national sample of veterans, schizophrenia and alcohol and drug use disorders were independently associated with an increased risk of all-cause mortality over a 9-year period.

Prospective study of externalizing and internalizing subtypes of posttraumatic stress disorder and their relationship to mortality among Vietnam veterans.

Posttraumatic stress disorder (PTSD) can be a complex disorder, and some studies have found that samples of individuals with PTSD contain subtypes that may relate to health outcomes. The goals were to replicate previously identified PTSD subtypes and examine how subtype membership relates to mortality. Data from the Vietnam Experience Study and a clinical sample of Vietnam veterans were combined (n = 5248) to address these research questions. Consistent with previous studies, 3 PTSD subtypes emerged: externalizers (n = 317), internalizers (n = 579), and low pathology (n = 280). Posttraumatic stress disorder diagnosis was associated with increased risk of all-cause and behavioral-cause (eg, homicide, suicide) mortality. Both externalizing and internalizing subtypes had higher mortality and were more likely to die from cardiovascular causes than those without PTSD. Externalizers were more likely to die from substance-related causes than those without PTSD. The value of considering possible PTSD subtypes is significant in that it may contribute to identifying more specific targets for treatment and rehabilitation in veterans with PTSD.

Factors associated with civilian mortality in Australian Vietnam veterans three decades after the war.

A prospective cohort study of a random sample of 1,000 Australian Army Vietnam veterans analyzed risk factors for postwar mortality using information from Army records and personal interview assessments of physical and mental health measured approximately 15 years earlier. This enabled examination of the role of combat, military service, and psychiatric status including post-traumatic stress disorder (PTSD) on postwar civilian mortality. Factors predicting mortality were identified using multivariate statistical methods including logistic and Cox regression. Mortality was associated principally with age, enlistment route (regular vs. national service conscripts), and conduct while in service in the whole cohort. Additional analysis using interview data revealed that mortality was predicted by age, smoking status, chronic diabetes, bronchitis and blood diseases, and treatment for cancer and heart disease. Psychiatric status including PTSD diagnosis was not associated with mortality. Veterans' mortality risk may be reduced by attention to smoking and alcohol both in-service and postservice.

Association Between Posttraumatic Stress Disorder and Mortality Among Responders and Civilians Following the September 11, 2001, Disaster.

Importance: Posttraumatic stress disorder (PTSD) has been associated with increased mortality, primarily in studies of veterans. The World Trade Center Health Registry (Registry) provides a unique opportunity to study the association between PTSD and mortality among a population exposed to the World Trade Center attacks in New York, New York, on September 11, 2001 (9/11). Objectives: To assess whether 9/11-related probable PTSD (PTSD) is associated with increased mortality risk, as well as whether this association differs when including repeated measures of PTSD over time vs a single baseline assessment. Design, Setting, and Participants: A longitudinal cohort study of 63 666 Registry enrollees (29 270 responders and 34 396 civilians) was conducted from September 5, 2003, to December 31, 2016, with PTSD assessments at baseline (wave 1: 2003-2004) and 3 follow-up time points (wave 2: 2006-2007, wave 3: 2011-2012, wave 4: 2015-2016). Data analyses were conducted from December 4, 2018, to May 20, 2019. Exposures: Posttraumatic stress disorder was defined using the 17-item PTSD Checklist-Specific (PCL-S) self-report measure (score ≥50) at each wave (waves 1-4). Baseline PTSD was defined using wave 1 PCL-S, and time-varying PTSD was defined using the PCL-S assessments from all 4 waves. Main Outcomes and Measures: Mortality outcomes were ascertained through National Death Index linkage from 2003 to 2016 and defined as all-cause, cardiovascular, and external-cause mortality. Results: Of 63 666 enrollees (38 883 men [61.1%]; mean [SD] age at 9/11, 40.4 [10.4] years), 6689 (10.8%) had PTSD at baseline (responders: 2702 [9.5%]; civilians: 3987 [12.0%]). Participants who were middle aged (2022 [12.5%]), female (3299 [13.8%]), non-Latino black (1295 [17.0%]), or Latino (1835 [22.2%]) were more likely to have PTSD. During follow-up, 2349 enrollees died (including 230 external-cause deaths and 487 cardiovascular deaths). Among all enrollees in time-varying analyses, PTSD was associated with all-cause, cardiovascular, and external-cause mortality, with adjusted hazard ratios (AHRs) of greater magnitude compared with analyses examining baseline PTSD. Among responders, time-varying PTSD was significantly associated with increased risk of all-cause (AHR, 1.91; 95% CI, 1.58-2.32), cardiovascular (AHR, 1.95; 95% CI, 1.25-3.04), and external-cause (AHR, 2.40; 95% CI, 1.47-3.91) mortality. Among civilians, time-varying PTSD was significantly associated with increased risk of all-cause (AHR, 1.54; 95% CI, 1.28-1.85), cardiovascular (AHR, 1.72; 95% CI, 1.15-2.58), and external-cause (AHR, 2.11; 95% CI, 1.06-4.19) mortality. Conclusions and Relevance: The risk of mortality differed in examination of baseline PTSD vs repeated measures of PTSD over time, suggesting that longitudinal data should be used where possible. Comparable findings between responders and civilians suggest that 9/11-related PTSD is associated with an increased mortality risk.

Association of Posttraumatic Stress and Depressive Symptoms With Mortality in Women.

Importance: Consistent evidence has found associations between posttraumatic stress disorder (PTSD) and increased risk of chronic disease and greater prevalence of health risk factors. However, the association between PTSD and all-cause mortality has not been thoroughly investigated in civilians. Objective: To investigate the association between PTSD symptoms, with or without comorbid depressive symptoms, and risk of death. Design, Setting, and Participants: This prospective cohort study was conducted using data on female US nurses in the Nurses' Health Study II followed up from 2008 to 2017. Women who responded to a 2008 questionnaire querying PTSD and depressive symptoms were included. Data were analyzed from September 2018 to November 2020. Exposures: Symptoms of PTSD, measured using the short screening scale for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) PTSD, and depression symptoms, measured using the Center for Epidemiologic Studies Depression Scale-10 in 2008. Main Outcomes and Measures: All-cause mortality was determined via National Death Index, US Postal Service, or report of participant's family. The hypothesis being tested was formulated after data collection. Trauma exposure and PTSD symptoms were jointly coded as no trauma exposure (reference), trauma and no PTSD symptoms, 1 to 3 PTSD symptoms (subclinical), 4 to 5 PTSD symptoms (moderate), and 6 to 7 PTSD symptoms (high). Results: Among 51 602 women (50 137 [97.2%] White individuals), the mean (range) age was 53.3 (43-64) years at study baseline in 2008. PTSD and probable depression were comorbid; of 4019 women with high PTSD symptoms, 2093 women (52.1%) had probable depression, while of 10 105 women with no trauma exposure, 1215 women (12.0%) had probable depression. Women with high PTSD symptoms and probable depression were at nearly 4-fold greater risk of death compared with women with no trauma exposure and no depression (hazard ratio [HR], 3.80; 95% CI, 2.65-5.45; P < .001). After adjustment for health factors, women with these conditions had a more than 3-fold increased risk (HR, 3.11; 95% CI, 2.16-4.47, P < .001). Women with subclinical PTSD symptoms without probable depression had increased risk of death compared with women with no trauma exposure and no depression (HR, 1.43; 95% CI, 1.06-1.93; P = .02). Among 7565 women with PTSD symptoms and probable depression, 109 deaths (1.4%) occurred for which we obtained cause of death information, compared with 124 such deaths (0.6% ) among 22 215 women with no depression or PTSD symptoms. Women with PTSD symptoms and probable depression, compared with women with no PTSD or depression, had higher rates of death from cardiovascular disease (17 women [0.22%] vs 11 women [0.05%]; P < .001), diabetes (4 women [0.05%] vs 0 women; P < .001), unintentional injury (7 women [0.09%] vs 7 women [0.03%]; P = .03), suicide (9 women [0.12%] vs 1 woman [<0.01%]; P < .001), and other causes of death (14 women [0.19%] vs 17 women [0.08%]; P = .01). Conclusions and Relevance: These findings suggest that at midlife, women with high PTSD symptoms and co-occurring probable depression are at increased risk of death compared with women without these disorders. Treatment of PTSD and depression in women with symptoms of both disorders and efforts to improve their health behaviors may reduce their increased risk of mortality.

The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD.

BACKGROUND: Chronic posttraumatic stress disorder (PTSD) is a disabling condition that generates considerable morbidity, mortality, and both medical and indirect social costs. Treatment options are limited. A novel therapy using 3,4-methylenedioxymethamphetamine (MDMA) has shown efficacy in six phase 2 trials. Its cost-effectiveness is unknown. METHODS AND FINDINGS: To assess the cost-effectiveness of MDMA-assisted psychotherapy (MAP) from the health care payer's perspective, we constructed a decision-analytic Markov model to portray the costs and health benefits of treating patients with chronic, severe, or extreme, treatment-resistant PTSD with MAP. In six double-blind phase 2 trials, MAP consisted of a mean of 2.5 90-minute trauma-focused psychotherapy sessions before two 8-hour sessions with MDMA (mean dose of 125 mg), followed by a mean of 3.5 integration sessions for each active session. The control group received an inactive placebo or 25-40 mg. of MDMA, and otherwise followed the same regimen. Our model calculates net medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Efficacy was based on the pooled results of six randomized controlled phase 2 trials with 105 subjects; and a four-year follow-up of 19 subjects. Other inputs were based on published literature and on assumptions when data were unavailable. We modeled results over a 30-year analytic horizon and conducted extensive sensitivity analyses. Our model calculates expected medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Future costs and QALYs were discounted at 3% per year. For 1,000 individuals, MAP generates discounted net savings of $103.2 million over 30 years while accruing 5,553 discounted QALYs, compared to continued standard of care. MAP breaks even on cost at 3.1 years while delivering 918 QALYs. Making the conservative assumption that benefits cease after one year, MAP would accrue net costs of $7.6 million while generating 288 QALYS, or $26,427 per QALY gained. CONCLUSION: MAP provided to patients with severe or extreme, chronic PTSD appears to be cost-saving while delivering substantial clinical benefit. Third-party payers are likely to save money within three years by covering this form of therapy.