Person:

VanderWeele, Tyler

Background: Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture. Objectives: 1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs. Data sources Pubmed and Science Citation Index. Study eligibility criteria, participants, and interventions Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events. Study appraisal and synthesis methods For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event. Results: We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference. Conclusions: The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.

Background: Little attention has been paid to potential relationships between mental health, trauma, and personal exposures to Ebola virus disease (EVD) and health behaviors in post-conflict West Africa. We tested a conceptual model linking mental health and trauma to EVD risk behaviors and EVD prevention behaviors. Methods and Findings: Using survey data from a representative sample in the Western Urban and Western Rural districts of Sierra Leone, this study examines associations between war exposures, post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, and personal EVD exposure (e.g., having family members or friends diagnosed with EVD) and EVD-related health behaviors among 1,008 adults (98% response rate) from 63 census enumeration areas of the Western Rural and Western Urban districts randomly sampled at the height of the EVD epidemic (January–April 2015). Primary outcomes were EVD risk behaviors (14 items, Cronbach’s α = 0.84) and EVD prevention behaviors (16 items, Cronbach’s α = 0.88). Main predictors comprised war exposures (8 items, Cronbach’s α = 0.85), anxiety (10 items, Cronbach’s α = 0.93), depression (15 items, Cronbach’s α = 0.91), and PTSD symptoms (16 items, Cronbach’s α = 0.93). Data were analyzed using two-level, population-weighted hierarchical linear models with 20 multiply imputed datasets. EVD risk behaviors were associated with intensity of depression symptoms (b = 0.05; 95% CI 0.00, 0.10; p = 0.037), PTSD symptoms (b = 0.10; 95% CI 0.03, 0.17; p = 0.008), having a friend diagnosed with EVD (b = −0.04; 95% CI −0.08, −0.00; p = 0.036), and war exposures (b = −0.09; 95% CI −0.17, −0.02; p = 0.013). EVD prevention behaviors were associated with higher anxiety (b = 0.23; 95% CI 0.06, 0.40; p = 0.008), having a friend diagnosed with EVD (b = 0.15; 95% CI 0.04, 0.27; p = 0.011), and higher levels of war exposure (b = 0.45; 95% CI 0.16, 0.74; p = 0.003), independent of mental health. PTSD symptoms were associated with lower levels of EVD prevention behavior (b = −0.24; 95% CI −0.43, −0.06; p = 0.009). Conclusions: In post-conflict settings, past war trauma and mental health problems are associated with health behaviors related to combatting EVD. The associations between war trauma and both EVD risk behaviors and EVD prevention behaviors may be mediated through two key mental health variables: depression and PTSD symptoms. Considering the role of mental health in the prevention of disease transmission may help fight continuing and future Ebola outbreaks in post-conflict Sierra Leone. This sample is specific to Freetown and the Western Area and may not be representative of all of Sierra Leone. In addition, our main outcomes as well as personal EVD exposure, war exposures, and mental health predictors rely on self-report, and therefore raise the possibility of common methods bias. However, the findings of this study may be relevant for understanding dynamics related to EVD and mental health in other major capital cities in the EVD-affected countries of West Africa.