Dramatic COVID-Related Jump in Z-Drug Prescriptions

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There has been a dramatic jump in prescriptions of benzodiazepines, Z-hypnotics, and serotonergic drugs related to the pandemic, new research shows.

Investigators found that prescriptions for Z-hypnotics and serotonergic agents increased from January 2020 to April 2020 for men and women and that prescriptions for benzodiazepine increased for women during those months.

The increase in use of Z-hypnotics, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs) was sustained throughout most of 2020. For all drug classes, rates of prescriptions were higher for women, and there were larger changes in rates over time.

“We hope this study highlights the disproportionate effect of the ongoing COVID-19 pandemic, sex as a priority to research in the COVID-19 pandemic, and the need for interventions to address these sex disparities in the consequences of the pandemic,” lead author Sadaf Milani, MD, MPH, assistant professor of internal medicine, University of Texas Medical Branch, Galveston, Texas, said in a press release.

The study was published online October 25 in JAMA Network Open.

Women Disproportionately Affected

The lockdown and shelter-in-place orders designed to mitigate the spread of COVID-19 have been “linked to a substantial increase” in mental health conditions that have “disproportionately affected women,” the researchers say. Data point to higher levels and greater increases in isolation, loneliness, alcohol use, anxiety, depressive disorders, and sleep difficulties in women in comparison with men.

“We were interested in seeing if the mental health impact of COVID-19 and associated mitigation measures exacerbated the already higher rates of mental health conditions among women,” Milani told Medscape Medical News.

To investigate, researchers drew on de-identified data from Clinformatics Data Mart, a large health insurance database, from January 1, 2018, to March 31, 2021.

The researchers analyzed prescriptions for benzodiazepines, Z-hypnotics, and serotonergic drugs for each enrollee. They summarized patient characteristics (age and region of residence) for the total sample and by sex.

Characteristic 2018 (n = 17,255,044) 2019 (n = 17,340,731) 2020 (n = 16,916,910) 2021 (n = 15,135,998)
Mean (SD) age 51.7 (19.5) years 52.5 (19.7) years 53.7 (19.8) years 56.2 (19.8) years
Female sex (n) 51.27% 51.60% 51.92% 52.45%


Women Disproportionately Affected

During the study period, the overall rates of benzodiazepine prescribing decreased, except for a slight increase from January 2020 to April 2020 (from 5.51% [95% CI, 5.60 – 5.63] to 5.00% [4.98 – 5.02]) among women.

Sex January 2018 (95% CI) March 2021 (95% CI)
Female 5.61% (5.60 – 5.63) 4.91% (4.90 – 4.93)
Male 3.03% (3.02 – 3.04) 2.66% (2.65 – 2.67)


For women, the prescription rates of benzodiazepines dropped by 0.03% monthly from January 2018 to January 2020, but then increased monthly by 0.06% until April 2020. It decreased again by 0.04% from April 2020 to March 2021. There were no significant changes in the slope of rates of benzodiazepine prescriptions for men during the study period.

On the other hand, Z-hypnotic prescriptions increased from the start of the pandemic (January 2020) in women and from February 2020 in men. The increase lasted through October 2020.

Month Women (95% CI) Men (95% CI)
January 2018 1.37% (1.36 – 1.38) 0.95% (.94 – .96)
March 2018 1.49% (1.48 –1.50) 1.03% (1.02 – 1.03)
January 2020 (women) February 2020 (men) 1.39% (1.38 – 1.40) 0.97% (.96% – .98%)
October 2020 1.46% (1.46 – 1.47) 1.00% (.96 – .98%)
March 2021 1.43% (1.42 – 1.44) 0.98% (.97 – .99)


For women, the monthly increase in Z-hypnotic prescriptions from January 2020 to October 2020 was 0.006%. For men, the monthly increase from January 2020 to October 2020 was 0.004%. From October 2020 to March 2021, the monthly decrease in prescribing rates also differed between women and men (0.009% and 0.005%, respectively).

Serotonergic prescriptions increased from January 2018 to April 2020 for men and October 2020 for women.

Month Women (95% CI) Men (95% CI)
January 2018 12.77% (12.75 – 12.80) 5.56% (5.44 – 5.58)
April 2020 (men) October 2020 (women) 15.18% (15.16 – 15.21) 6.73% (6.71 – 6.75)
February 2021 14.75% (14.72 – 14.77) 6.57% (6.55 – 6.59)


Again, there were differences in the monthly changes in prescription rates of SSRIs/SNRIs between men and women. For women, the monthly increase was 0.07% from January 2018 to October 2020, followed by a 0.05% decrease from October 2020 to March 2021.

For men, the rates increased by 0.03% monthly from January 2018 to January 2020 and continued to increase by 0.1% monthly from January 2020 to April 2020, after which they declined by 0.01% monthly through March 2021.

“There are multiple reasons that may explain why women were more affected than men by the COVID-19 pandemic and related mitigation measures,” said Milani.

“Most caregivers are women, and with the closing of schools during the pandemic, the burden of childcare fell largely on women — even in couples in dual-career households,” she said. Women were also more affected by joblessness, Milani added.

“Practicing clinicians should exercise caution with long-term use of Z-drugs, and they should strongly consider nonpharmacologic and behavioral approaches as safer and effective alternatives for insomnia and other sleep disorders,” said Milani.

Screening for mental health disorders using validated tools should become routine in clinical practice, she said.

This is “especially critical in moments of natural disasters — infectious pandemics and extreme weather events, such as hurricanes — as our study suggests that those disasters exact a higher mental and psychological toll on women than men,” she said.

Medication Alternatives Needed

Commenting on the study for Medscape Medical News, Tyler Varisco, PhD, PharmD, research assistant professor in the Prescription Drug Misuse Education and Research Center, University of Houston College of Pharmacy, Houston, Texas, said it is “important to remember that this reflects ongoing trends in treatment of pervasive mental health conditions that we need to monitor, even when the pandemic changes course and we begin to live with endemic COVID-19.”

Varisco, who was not involved with the study, said it will be “interesting to see if we return to our prepandemic mental health baseline as we learn to live with COVID.”

An important take-home message is that “we need to find ways to extend help without relying completely on medication, and a multimodal approach to mental health is preferred,” he said.

“Increased prescribing suggests that we’ve wandered away from that and are relying on medications more than we were prior to the pandemic to manage mental health conditions,” he added.

The study was supported by grants from the University of Texas Medical Branch Claude D. Pepper Older Americans Independence Center; the Texas Resource Center for Minority Aging Research from the National Institute on Aging; the Building Interdisciplinary Research Careers in Women’s Health Program, the Office of the Director, the National Institute of Allergy and Infectious Diseases, the National Institutes of Health; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the National Institute on Drug Abuse. Milani received 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. The other authors’ disclosures are listed on the original article. Varisco reports no relevant financial relationships.

JAMA Netw Open. Published online October 25, 2021. Full text

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