Recent Food and Drug Administration (FDA) warnings and medical association guidelines focus on potential health risks associated with psychotropic medications, suggesting modifications for clinical practice. These types of evidence-based policies can have an important impact on public health and safety. The VA Pharmacy Benefits Management Services (VA PBM) is responsible for initiating VA responses to FDA warnings. Despite VA PBM's use of several approaches to convey warnings to Veterans Integrated Service Networks (VISNs), VA facilities, and providers, much remains unknown about the multiple contextual and organizational factors influencing responsiveness to these warnings. A better understanding of VA system and provider level responsiveness could lead to developing and sharing best practices and informing future strategies to improve warning adoption, thereby improving patient care and population safety.
Given that considerable VA facility-level variation exists in psychotropic prescribing practices, the overarching goal of this study is to examine multilevel responses to external warnings regarding psychotropic medications. We seek to understand variation in the adoption of warnings by VISNs, VA facilities, and providers, and the effect of varying levels of pharmacy integration on response to warnings. We use two examples of recent warnings designed to mitigate risks associated with psychotropic medications: 1) sudden cardiac events associated with high doses citalopram [Celexa]; and 2) impaired driving associated with zolpidem [Ambien]. In this context, we will address the following three specific aims: Aim 1: To assess and describe PBM and VISN-level responsiveness and variation in responsiveness to warnings regarding psychotropic medications. Aim 2: To assess prescribing patterns before and after warnings regarding psychotropic medications. Aim 3: To understand specific strategies used by facilities and providers with high response to warnings and barriers encountered by facilities and providers with low response to warnings.
Using both qualitative (theory-driven semi-structured interviews) and quantitative methods (surveys and administrative data), we will evaluate multiple factors that could influence facility and provider responsiveness to warnings. This study will be the first mixed methods longitudinal study of warnings for psychotropic medications in a large national health system. Aim 1 will detail the processes by which VHA prescribing policies and guidance were developed, how dissemination was accomplished, and perceived barriers and facilitators to adoption across the system, based on semi-structured interviews with national VA PBM leaders and pharmacy leaders at each VISN (N=21). Aim 2 will employ segmented regression techniques using administrative data pre- and post-warning to identify changes in psychotropic medication prescriptions and patient health monitoring in VHA by VISN and facility. Aim 3 will detail processes by which facilities and providers changed practice in response to warnings and PBM dissemination efforts. Interviews will be conducted with facility leaders (pharmacy, primary care, mental health) in Aim 3A, and surveys will be conducted with primary care providers (PCPs), and psychiatrists in Aim 3B, all of whom will be intentionally sampled based on findings from Aims 1 and 2. Methods developed and refined in this project will be applicable to a broad range of policies for mental health treatment and pharmacosurveillance.
We have found that high dose citalopram use changed abruptly following the 2011 and 2012 FDA warnings, with decreases in high dose use. We found increases in the use of sertraline and other antidepressants during this time suggesting possible substitution of citalopram.
We found that among patients prescribed high dose citalopram, EKG monitoring increased from 9% before the start of the first FDA warning, to a peak of 12.6% among patients 18-60 years old, and from 14% to 19.4% for patients 61-100 years old, respectively. Following the 2nd FDA warning in 2012, EKG monitoring declined, returning to pre-warning levels across both age groups.
We found that higher than recommended dose zolpidem use decreased immediately after each warning and was 2% lower in 2014 among men. For women who were prescribed zolpidem, nearly half remained on higher than recommended dose following the drug safety warnings. We found that use of any dose zolpidem quadrupled after the 2007 warning. After the 2013 FDA warning, any dose zolpidem use declined, but remained at more than three times the use prior to the 2007 warning by VHA.
Of the 139,525 new VA zolpidem users between 1/1/2013 and 6/3/2014 we found that <1% of males and 41% of women used high-doses within 180 days of initiation, and 20% continued to use long-term. Prior year use of other sleep medications was associated with both high-dose and long-term use. Substance abuse/dependence was associated with high-dose use in women. In both sexes, Hispanic ethnicity and non-White races were less likely to use long-term, whereas those with ICD-9-CM defined psychiatric and sleep disorder diagnoses were more likely to use long-term.
Likely impact derives from bringing together unprecedented data resources, qualitative and quantitative methods, new applications of organizational theories, and diverse investigator expertise. This work could improve clinical care and patient safety by enhancing our understanding of how pharmaceutical and therapeutic alerts are acted on in the system, directly benefiting VA practice and patients.
- Kim HM, Gerlach LB, Yosef M, Stano C, Conroy DA, Valenstein M, Pfeiffer PN, Sales AE, Zivin K. Responsiveness of Veterans Affairs Health Care System to Zolpidem Safety Warnings. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2018 Jul 15; 14(7):1135-1141.
- Gerlach LB, Kim HM, Yosef M, Kales HC, Henry J, Zivin K. Electrocardiogram Monitoring After the Food and Drug Administration Warnings for Citalopram: Unheeded Alerts?. Journal of the American Geriatrics Society. 2018 Aug 1; 66(8):1562-1566.
- Gerlach LB, Kim HM, Yosef M, Sales AE, Stano C, Kales HC, Zivin K. Assessing Responsiveness of Health Systems to Drug Safety Warnings. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2018 Apr 1; 26(4):476-483.