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The American Journal of Managed Care March 2019
Fragmented Ambulatory Care and Subsequent Emergency Department Visits and Hospital Admissions Among Medicaid Beneficiaries
Lisa M. Kern, MD, MPH; Joanna K. Seirup, MPH; Mangala Rajan, MBA; Rachel Jawahar, PhD, MPH; and Susan S. Stuard, MBA
Incorrect and Missing Author Initials in Affiliations and Authorship Information
From the Editorial Board: Austin Frakt, PhD
Austin Frakt, PhD
Implications of Eligibility Category Churn for Pediatric Payment in Medicaid
Deena J. Chisolm, PhD; Sean P. Gleeson, MD, MBA; Kelly J. Kelleher, MD, MPH; Marisa E. Domino, PhD; Emily Alexy, MPH; Wendy Yi Xu, PhD; and Paula H. Song, PhD
Factors Influencing Primary Care Providers’ Decisions to Accept New Medicaid Patients Under Michigan’s Medicaid Expansion
Renuka Tipirneni, MD, MSc; Edith C. Kieffer, PhD, MPH; John Z. Ayanian, MD, MPP; Eric G. Campbell, PhD; Cengiz Salman, MA; Sarah J. Clark, MPH; Tammy Chang, MD, MPH, MS; Adrianne N. Haggins, MD, MSc; Erica Solway, PhD, MPH, MSW; Matthias A. Kirch, MS; and Susan D. Goold, MD, MHSA, MA
Did Medicaid Expansion Matter in States With Generous Medicaid?
Alina Denham, MS; and Peter J. Veazie, PhD
Access to Primary and Dental Care Among Adults Newly Enrolled in Medicaid
Krisda H. Chaiyachati, MD, MPH, MSHP; Jeffrey K. Hom, MD, MSHP; Charlene Wong, MD, MSHP; Kamyar Nasseh, PhD; Xinwei Chen, MS; Ashley Beggin, BS; Elisa Zygmunt, MSW; Marko Vujicic, PhD; and David Grande, MD, MPA
Medicare Annual Wellness Visit Association With Healthcare Quality and Costs
Adam L. Beckman, BS; Adan Z. Becerra, PhD; Anna Marcus, BS; C. Annette DuBard, MD, MPH; Kimberly Lynch, MPH; Emily Maxson, MD; Farzad Mostashari, MD, ScM; and Jennifer King, PhD
Common Elements in Opioid Use Disorder Guidelines for Buprenorphine Prescribing
Timothy J. Atkinson, PharmD, BCPS, CPE; Andrew J.B. Pisansky, MD, MS; Katie L. Miller, PharmD, BCPS; and R. Jason Yong, MD, MBA
Specialty Care Access for Medicaid Enrollees in Expansion States
Justin W. Timbie, PhD; Ashley M. Kranz, PhD; Ammarah Mahmud, MPH; and Cheryl L. Damberg, PhD
Currently Reading
Gender Differences in Prescribing of Zolpidem in the Veterans Health Administration
Guneet K. Jasuja, PhD; Joel I. Reisman, AB; Renda Soylemez Wiener, MD, MPH; Melissa L. Christopher, PharmD; and Adam J. Rose, MD, MSc
Health Insurance Literacy: Disparities by Race, Ethnicity, and Language Preference
Victor G. Villagra, MD; Bhumika Bhuva, MA; Emil Coman, PhD; Denise O. Smith, MBA; and Judith Fifield, PhD

Gender Differences in Prescribing of Zolpidem in the Veterans Health Administration

Guneet K. Jasuja, PhD; Joel I. Reisman, AB; Renda Soylemez Wiener, MD, MPH; Melissa L. Christopher, PharmD; and Adam J. Rose, MD, MSc
We found inappropriate prescribing of zolpidem, in terms of both guideline-discordant dosage and coprescribing with benzodiazepines, with female veterans affected more than male veterans.
ABSTRACT

Objectives: Use of nonbenzodiazepine sedative hypnotics, especially zolpidem, has grown substantially, raising concerns about safety. Here, we evaluated prescribing patterns of zolpidem in the Veterans Health Administration.

Study Design: A cross-sectional study of veterans receiving zolpidem in the outpatient setting from October 1, 2011, to September 30, 2016.

Methods: The study population consisted of 500,332 zolpidem users (58,598 women and 441,734 men) and a random 10% sample (n = 631,449) of nonusers. We examined 2 outcomes related to inappropriate prescribing: high-dose zolpidem prescribing and overlap with benzodiazepines. We generated interrupted time series and logistic regression models to analyze these outcomes in men and women separately.

Results: In 2016, 29.7% of female veterans received an inappropriately high guideline-discordant dosage compared with 0.1% of male veterans (P <.001 for all reported comparisons). Furthermore, more women than men had overlapping benzodiazepine and zolpidem prescriptions (18.8% vs 14.3%). In fully adjusted models, inappropriately high doses were more commonly received by younger women (adjusted odds ratios [AORs]: 2.75 for 21-39 years and 2.97 for 40-49 years compared with ≥80 years) and women with substance use disorder (AOR, 1.48). In the second inappropriateness outcome models, women with anxiety (AOR, 2.28) or schizophrenia (AOR, 2.05) and men with cancer (AOR, 1.42), anxiety (AOR, 2.66), or schizophrenia (AOR, 2.46) were more likely to receive an overlapping prescription of zolpidem and benzodiazepines.

Conclusions: We found evidence of inappropriate zolpidem prescribing among veterans, particularly women. Greater understanding of the drivers of this inappropriate prescribing is necessary to develop interventions to promote safer, more guideline-concordant prescribing.

Am J Manag Care. 2019;25(3):e58-e65
Takeaway Points

Gender-specific guidelines have been recommended for appropriate zolpidem prescribing to address patient safety concerns.
  • The present study suggests that a higher proportion of female veterans received an inappropriately high zolpidem dosage and had overlapping zolpidem and benzodiazepine prescriptions compared with male veterans.
  • Findings have implications both for patient safety and promoting guideline-concordant prescribing in female zolpidem users.
  • Managed care decision makers may wish to query adherence to guidelines and raise awareness to drive practice changes and reduce morbidity and mortality related to preventable adverse events in their systems of care.
Zolpidem, a nonbenzodiazepine sedative hypnotic, is extensively prescribed in the United States1,2 for short-term treatment of insomnia. However, there have been growing concerns associated with its use, including higher risks of falls and fractures,3,4 motor vehicle collisions,5 central nervous system–associated adverse drug reactions,6 dependence,7 and mortality.8 In fact, it has been shown that the mortality implications of taking zolpidem are equivalent to those associated with a benzodiazepine.9 Clinically significant drug interactions of zolpidem with benzodiazepines are associated with increased hospitalizations.10 To add to the complexity, gender differences have been noted, with women reporting greater sensitivity than men to the sedative effects of zolpidem.11

These safety concerns prompted the FDA in 2013 to recommend cutting doses prescribed to women in half, specifically from 10 mg immediate release (IR) daily to a maximum of 5 mg/day and from 12.5 mg controlled release (CR) daily to 6.25 mg/day.12 Usually prescribed for a 30-day period, the IR formulation dissolves much more rapidly than the CR formulation to cause sedation facilitating the induction of sleep.13 Although there was also a recommendation to extend this dose reduction to men, the guidelines remained unchanged for men (5 mg or 10 mg IR and 6.25 mg or 12.5 mg CR). This mandate of a gender-specific guideline for zolpidem was due to the fact that women metabolize the same dose of zolpidem more slowly than men, resulting in 50% higher serum levels.14 Previous studies have found increased compliance among providers, specifically midlevel and physician providers, with reduced-dose zolpidem in women after the FDA-mandated labeling changes.15,16 Although adherence to guidelines was attributed to change in prescribing habits of the providers, it could not be ascertained whether it was driven by the drug safety communication from the FDA or individual patient factors. However, these studies included relatively small sample sizes; they did not evaluate the proportion of women who were still being prescribed an inappropriate dosage after the FDA guidance, nor did they examine predictors of this inappropriate outcome.

In line with this FDA recommendation, the national Veterans Health Administration (VHA) Pharmacy Benefits Management (PBM) Service issued a similar directive to lower the doses of zolpidem in women in 2013.17 However, little is known about zolpidem prescribing patterns in the VHA. Therefore, the goal of this study was to examine utilization trends and inappropriate prescribing of zolpidem in accordance with PBM guidelines in male and female veterans in the VHA. We expected significant differences in inappropriate zolpidem prescribing in male and female veterans by age, with women potentially being more likely to receive zolpidem inappropriately.

METHODS

The study was approved by the Institutional Review Board of the Bedford Veterans Affairs Medical Center. We examined demographic, diagnostic, and prescription data of patients receiving outpatient prescriptions for zolpidem at any VHA site between October 1, 2011, and September 30, 2016.

Study Population

We examined all patients who received zolpidem (n = 500,332; 441,734 men and 58,598 women) between fiscal year (FY) 2012 and FY 2016. We defined a zolpidem user as a patient who received 3 or more days of continuous zolpidem prescription during the study period. Additionally, we examined a random 10% sample of patients who did not receive zolpidem (n = 631,449). We also used the full study population (N = 1,131,781) as a basis for calculating prevalence rates. The index date for zolpidem users was the earliest prescription of zolpidem they received in the entire study period.

Independent Variables

We examined the sociodemographic factors gender, age, race, Hispanic ethnicity, marital status, VHA co-payment for prescription drugs based on VHA eligibility status, FY of zolpidem prescription, US region where the patient received care, and the urban versus rural status of the facility where the index prescription was written. These variables, and in particular gender and age, have been previously linked to healthcare utilization.18 We also evaluated a number of physical and mental health conditions that have been shown to be associated with zolpidem use.19-22 The presence of these conditions was determined from inpatient and outpatient diagnoses using International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes, using a 1-year look-back period prior to the date of the index prescription (eAppendix [available at ajmc.com]). We considered a condition to be present when there were at least 2 diagnostic codes for the condition separated by 7 or more days.


 
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