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Trends in the Use of Benzodiazepines, Z-Hypnotics, and Serotonergic Drugs Among US Women and Men Before and During the COVID-19 Pandemic

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What are the changes in prescribing rates in men and women of benzodiazepines, Z-hypnotics, and serotonergic drugs during the COVID-19 pandemic (2020 and 2021) compared with prior years (2018 and 2019)?

Findings  This cohort study of US adults (15.1 million to 17.3 million depending on the year studied) found an increase in Z-hypnotic and serotonergic drug prescriptions in both men and women along with an increase in benzodiazepine prescriptions in women at the start of the COVID-19 pandemic.

Meaning  These findings suggest a substantial association of COVID-19–associated social isolation, stay-at-home orders, and other COVID-related mitigation measures with mental health issues, especially among women.


Importance  The ongoing COVID-19 pandemic and associated mitigation measures have disrupted access to psychiatric medications, particularly for women.

Objective  To assess the sex differences in trends in the prescribing of benzodiazepines, Z-hypnotics and serotonergic (selective serotonin reuptake inhibitors [SSRIs] and serotonin and norepinephrine reuptake inhibitors [SNRIs]), which are commonly prescribed for anxiety, insomnia, and depression.

Design, Setting, and Participants  This cohort study used data from Clinformatics Data Mart, one of the largest commercial health insurance databases in the US. Enrollees 18 years or older were required to have complete enrollment in a given month during our study period, January 1, 2018, to March 31, 2021, to be included for that month.

Main Outcomes and Measures  Prescription of a benzodiazepine, Z-hypnotic, or SSRI or SNRI. For each month, the percentage of patients with benzodiazepine, Z-hypnotic, or SSRI or SNRI prescriptions by sex was calculated.

Results  The records of 17 255 033 adults (mean [SD] age, 51.7 [19.5] years; 51.3% female) were examined in 2018, 17 340 731 adults (mean [SD] age, 52.5 [19.7] years; 51.6% female) in 2019, 16 916 910 adults (mean [SD] age, 53.7 [19.8] years; 51.9% female) in 2020, and 15 135 998 adults (mean [SD] age, 56.2 [19.8] years; 52.5% female) in 2021. Compared with men, women had a higher rate of prescriptions for all 3 drugs classes and had larger changes in prescription rates over time. Benzodiazepine prescribing decreased from January 2018 (women: 5.61%; 95% CI, 5.60%-5.63%; men: 3.03%; 95% CI, 3.02%-3.04%) to March 2021 (women: 4.91%; 95% CI, 4.90%-4.93%; men: 2.66%; 95% CI, 2.65%-2.67%), except for a slight increase in April 2020 among women. Z-hypnotic prescribing increased from January 2020 for women (1.39%; 95% CI, 1.38%-1.40%) and February 2020 for men (0.97%; 95% CI, 0.96%-0.98%) to October 2020 (women: 1.46%; 95% CI, 1.46%-1.47%; men: 1.00%; 95% CI, 0.99%-1.01%). Prescribing of SSRIs and SNRIs increased from January 2018 (women: 12.77%; 95% CI; 12.75%-12.80%; men: 5.56%; 95% CI, 5.44%-5.58%) to April 2020 for men (6.73%; 95% CI, 6.71%-6.75%) and October 2020 for women (15.18%; 95% CI, 15.16%-15.21%).

Conclusions and Relevance  In this cohort study, coinciding with the COVID-19 pandemic onset was an increase in Z-hypnotic as well as SSRI and SNRI prescriptions in both men and women along with an increase in benzodiazepine prescriptions in women, findings that suggest a substantial mental health impact of COVID-19–associated mitigation measures.

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Article Information

Accepted for Publication: August 21, 2021.

Published: October 25, 2021. doi:10.1001/jamanetworkopen.2021.31012

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Milani SA et al. JAMA Network Open.

Corresponding Author: Sadaf Arefi Milani, PhD, MPH, Department of Internal Medicine–Geriatrics and Palliative Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77550-0177 (samilani@utmb.edu).

Author Contributions: Ms Chen and Dr Kuo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Raji, Kuo.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Milani, Raji.

Critical revision of the manuscript for important intellectual content: Raji, Chen, Kuo.

Statistical analysis: Chen.

Obtained funding: Raji, Kuo.

Supervision: Raji, Kuo.

Conflict of Interest Disclosures: Dr Milani reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, nonfinancial support from the University of Texas Medical Branch Claude D. Pepper Older Americans Independence Center, and grants from the Texas Resource Center for Minority Aging Research during the conduct of the study. Drs Raji and Kuo reported receiving grants from the National Institute on Drug Abuse, National Institutes of Health, and serving as multiple principal investigators on research with the National Institute on Drug Abuse, National Institutes of Health, during the conduct of the study. No other disclosures were reported.

Funding/Support: This work is supported by grant P30AG024832 from the University of Texas Medical Branch Claude D. Pepper Older Americans Independence Center and grant P30AG059301 from the Texas Resource Center for Minority Aging Research from the National Institute on Aging; research career development award K12HD052023 from the Building Interdisciplinary Research Careers in Women’s Health Program, Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and grant R01‐DA039192 from the National Institute on Drug Abuse (Drs Raji and Kuo).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Cucinotta  D , Vanelli  M .  WHO declares COVID-19 a pandemic.   Acta Biomed. 2020;91(1):157-160. doi:10.23750/abm.v91i1.9397PubMedGoogle Scholar
Lasry  A , Kidder  D , Hast  M ,  et al. Timing of community mitigation and changes in reported COVID-19 and community mobility—four U.S. metropolitan areas, February 26-April 1, 2020. MMWR Morbid Mortal Wkly Rep. 2020;69(15):451-457. doi:10.15585/mmwr.mm6915e2
Bambra  C , Riordan  R , Ford  J , Matthews  F .  The COVID-19 pandemic and health inequalities.   J Epidemiol Community Health. 2020;74(11):964-968. doi:10.1136/jech-2020-214401PubMedGoogle Scholar
Nalbandian  A , Sehgal  K , Gupta  A ,  et al Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z
Moreno  C , Wykes  T , Galderisi  S ,  et al.  How mental health care should change as a consequence of the COVID-19 pandemic.   Lancet Psychiatry. 2020;7(9):813-824. doi:10.1016/S2215-0366(20)30307-2 PubMedGoogle ScholarCrossref
Fullana  MA , Hidalgo-Mazzei  D , Vieta  E , Radua  J . Coping behaviors associated with decreased anxiety and depressive symptoms during the COVID-19 pandemic and lockdown. J Affect Disord. 2020;275:80-81. doi:10.1016/j.jad.2020.06.027
Pfefferbaum  B , North  CS . Mental health and the Covid-19 pandemic. N Engl J Med. 2020;383(6):510-512. doi:10.1056/NEJMp2008017
Brooks  SK , Webster  RK , Smith  LE ,  et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020;395(10227):912-920. doi:10.1016/S0140-6736(20)30460-8
McGinty  EE , Presskreischer  R , Han  H , Barry  CL .  Psychological distress and loneliness reported by US adults in 2018 and April 2020.   JAMA. 2020;324(1):93-94. doi:10.1001/jama.2020.9740 PubMedGoogle ScholarCrossref
Panchal  N , Kamal  R, , K, Cox, C. The Implications of COVID-19 for mental health and substance use. KFF Issue Brief. Accessed May 3, 2021. https://www.kff.org/coronavirus-covid-19/issue-brief/the-implications-of-covid-19-for-mental-health-and-substance-use/
Pierce  M , Hope  H , Ford  T ,  et al.  Mental health before and during the COVID-19 pandemic: a longitudinal probability sample survey of the UK population.   Lancet Psychiatry. 2020;7(10):883-892. doi:10.1016/S2215-0366(20)30308-4 PubMedGoogle ScholarCrossref
Kämpfen  F , Kohler  IV , Ciancio  A , Bruine de Bruin  W , Maurer  J , Kohler  H-P .  Predictors of mental health during the Covid-19 pandemic in the US: role of economic concerns, health worries and social distancing.   PLoS One. 2020;15(11):e0241895. doi:10.1371/journal.pone.0241895 PubMedGoogle Scholar
Galea  S , Merchant  RM , Lurie  N .  The mental health consequences of COVID-19 and physical distancing: the need for prevention and early intervention.   JAMA Intern Med. 2020;180(6):817-818. doi:10.1001/jamainternmed.2020.1562 PubMedGoogle ScholarCrossref
Killgore  WDS , Cloonan  SA , Taylor  EC , Dailey  NS .  Loneliness: a signature mental health concern in the era of COVID-19.   Psychiatry Res. 2020;290:113117-113117. doi:10.1016/j.psychres.2020.113117 PubMedGoogle ScholarCrossref
Holland  KM , Jones  C , Vivolo-Kantor  AM ,  et al.  Trends in US emergency department visits for mental health, overdose, and violence outcomes before and during the COVID-19 pandemic.   JAMA Psychiatry. 2021;78(4):372-379. doi:10.1001/jamapsychiatry.2020.4402 PubMedGoogle ScholarCrossref
Czeisler  MÉ , Lane  RI , Petrosky  E ,  et al.  Mental health, substance use, and suicidal ideation during the COVID-19 pandemic—United States, June 24-30, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(32):1049-1057. doi:10.15585/mmwr.mm6932a1 PubMedGoogle ScholarCrossref
Vahratian  A , Blumberg  SJ , Terlizzi  EP , Schiller  JS .  Symptoms of anxiety or depressive disorder and use of mental health care among adults during the COVID-19 pandemic—United States, August 2020-February 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(13):490-494. doi:10.15585/mmwr.mm7013e2 PubMedGoogle ScholarCrossref
Guadagni  V , Umilta’  A , Iaria  G . Sleep quality, empathy, and mood during the isolation period of the COVID-19 pandemic in the Canadian population: females and women suffered the most. Front Glob Womens Health. 2020;1(13):1-10. doi:10.3389/fgwh.2020.585938
Connor  J , Madhavan  S , Mokashi  M ,  et al. Health risks and outcomes that disproportionately affect women during the Covid-19 pandemic: a review. Soc Sci Med. 2020;266:113364. doi:10.1016/j.socscimed.2020.113364
Power  K . The COVID-19 pandemic has increased the care burden of women and families. Sustainability Sci Prac Policy. 2020;16(1):67-73. doi:10.1080/15487733.2020.1776561
Kantamneni  N . The impact of the COVID-19 pandemic on marginalized populations in the United States: a research agenda. J Vocational Behav. 2020;119:103439. doi:10.1016/j.jvb.2020.103439
National Institute of Mental Health. Women and Mental Health. Accessed May 3, 2021. https://www.nimh.nih.gov/health/topics/women-and-mental-health/
US Census Bureau. Full-time, year-round workers and median earnings in the past 12 months by sex and detailed occupation: 2019 American Community Survey. 2019. Accessed May 3, 2021. https://www.census.gov/data/tables/time-series/demo/industry-occupation/median-earnings.html
Diaz-Ordaz  L .  Real work: domestic workers’ exclusion from the protections of labor laws.  Buffalo Journal of Gender, Law and Social Policy. 2010;19:107.
Adelman  RD , Tmanova  LL , Delgado  D , Dion  S , Lachs  MS .  Caregiver burden: a clinical review.   JAMA. 2014;311(10):1052-1060. doi:10.1001/jama.2014.304 PubMedGoogle ScholarCrossref
Graves  L. Women’s domestic burden just got heavier with the coronavirus. The Guardian. March 16, 2020. Accessed May 21, 2021. https://www.theguardian.com/us-news/2020/mar/16/womens-coronavirus-domestic-burden
Ewing-Nelson  C. All of the jobs lost in December were women’s jobs. National Women’s Law Center. Accessed May 3, 2021. https://nwlc.org/wp-content/uploads/2021/01/December-Jobs-Day.pdf
Physicians’ Desk Reference. Red Book 2010: Pharmacy’s Fundamental Reference. 114th ed. PDR Network; 2010.
Statistical Methodology and Applications Branch and Data Modeling Branch, Surveillance Research Program. Joinpoint Regression Program [software program]. version National Cancer Institute; 2017. Accessed April 28, 2021. https://surveillance.cancer.gov/joinpoint/
Czeisler  MÉ , Lane  RI , Wiley  JF , Czeisler  CA , Howard  ME , Rajaratnam  SMW .  Follow-up survey of US adult reports of mental health, substance use, and suicidal ideation during the COVID-19 pandemic, September 2020.   JAMA Netw Open. 2021;4(2):e2037665-e2037665. doi:10.1001/jamanetworkopen.2020.37665 PubMedGoogle ScholarCrossref
Kolla  BP , Lovely  JK , Mansukhani  MP , Morgenthaler  TI .  Zolpidem is independently associated with increased risk of inpatient falls.   J Hosp Med. 2013;8(1):1-6. doi:10.1002/jhm.1985 PubMedGoogle ScholarCrossref
Hampton  LM , Daubresse  M , Chang  HY , Alexander  GC , Budnitz  DS .  Emergency department visits by adults for psychiatric medication adverse events.   JAMA Psychiatry. 2014;71(9):1006-1014. doi:10.1001/jamapsychiatry.2014.436 PubMedGoogle ScholarCrossref
Moore  TJ , Mattison  DR .  Assessment of Patterns of Potentially Unsafe Use of Zolpidem.   JAMA Intern Med. 2018;178(9):1275-1277. doi:10.1001/jamainternmed.2018.3031 PubMedGoogle ScholarCrossref
US Food and Drug Administration. FDA drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. 2016. Accessed May 12, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or
US Food and Drug Administration. FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class. 2020. Accessed May 12, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class
American Geriatrics Society. Choosing Wisely. Ten Things Clinicians and Patients Should Question. 2015. Accessed May 12, 2021. https://www.choosingwisely.org/societies/american-geriatrics-society/
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