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. 2022 Apr 14:13:874724.
doi: 10.3389/fneur.2022.874724. eCollection 2022.

Use of Benzodiazepines and Z-Drugs in Multiple Sclerosis

Ruth Ann Marrie  1   2 , John D Fisk  3 , Randy Walld  4 , James M Bolton  5 , Jitender Sareen  5 , Scott B Patten  6 , Alexander Singer  7 , Lisa M Lix  2 , Carol A Hitchon  1 , Renée El-Gabalawy  8   9 , Alan Katz  3   4   7 , James J Marriott  1 , Charles N Bernstein  1 ; CIHR Team in Defining the Burden Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease
Affiliations

Use of Benzodiazepines and Z-Drugs in Multiple Sclerosis

Ruth Ann Marrie et al. Front Neurol. .

Abstract

Objective: Use of benzodiazepines and Z-drugs (non-benzodiazepine sedative hypnotics) is controversial due to adverse health outcomes in the general population. However, little is known about their use in people with multiple sclerosis (MS). We estimated the incidence and prevalence of benzodiazepine and Z-drug use (jointly BZD) in the MS population as compared to an age-, sex- and geographically-matched population without MS, and examined the association of mood/anxiety disorders with the use of BZD over a twenty-year period.

Methods: Using administrative data from Manitoba, Canada, we identified 2,985 persons with incident MS and 14,891 persons without MS matched 5:1 on sex, birth year and region. We applied validated case definitions to identify persons with any mood/anxiety disorder. Dispensations of BZD were identified. To assess the association between MS, mood/anxiety disorders and BZD use we constructed generalized linear models adjusting for age, sex, index year, socioeconomic status, urban/rural residence, physical comorbidities, and health care use. We also examined patterns of BZD use.

Results: In 2016, the crude incidence of benzodiazepine use in the MS cohort was 2.10% (95%CI: 1.43-2.98%), 1.49-fold higher than in the non-MS cohort (1.41%; 95%CI: 1.18-1.67%). The crude incidence of Z-drug use in the MS cohort was 1.77% (95%CI: 1.20-2.51%), 1.78-fold higher than in the non-MS cohort (0.99%; 95%CI: 0.81-1.21%). After adjusting for covariates, among individuals without an active mood/anxiety disorder, the MS cohort had a 39% increased incidence rate of benzodiazepine use and a 72% increased incidence rate of Z-drug use as compared to the non-MS cohort. Among individuals with an active mood/anxiety disorder, the incidence of BZD use did not differ between the MS and non-MS cohorts. A higher proportion of people with MS used BZD for ≥6 months than people without MS.

Conclusion: Use of BZD is more common in people with MS than in general population controls, and use of these agents is in persons with MS is often chronic.

Keywords: Z-drugs; benzodiazepines; cohort; multiple sclerosis; psychiatric comorbidity.

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Conflict of interest statement

RM receives research funding from: CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC. She is supported by the Waugh Family Chair in Multiple Sclerosis and is a co-investigator on a study funded in part by Roche and Biogen Idec. JB receives research funding from CIHR, Brain and Behavior Research Foundation and the MS Society of Canada. JS receives research funding from CIHR and holds stocks in Johnson and Johnson. SP receives research funding from CIHR, the MS Society of Canada, Roche, Biogen and the Government of Alberta. AS has received financial and in-kind support from an IBM/CIMVHR Advanced Analytics Grant and Calian Inc. LL receives research funds from CIHR and the Arthritis Society. CH has research funds for unrelated studies from UCB Canada and Pfizer. RE-G receives research funds from CIHR, University of Manitoba Start-Up Funds. AK receives research funds from CIHR, the Heart and Stroke Foundation and Research Manitoba. JF receives research funds from CIHR, the MS Society of Canada, Crohn's and Colitis Canada, Research Nova Scotia; consultation and distribution royalties from MAPI Research Trust. JM has conducted clinical trials for Biogen Idec and Roche, and receives research funding from the MS Society of Canada, the MS Scientific Foundation and Research Manitoba. CB has consulted to Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharmaceuticals, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada, and has received unrestricted educational grants from Abbvie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. He has been on speaker's bureaus of Abbvie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Age- and sex-standardized* annual incidence of benzodiazepine and Z-drug use per 100 persons. *To 2010 Canadian population.
Figure 2
Figure 2
Average annual incidence (95% CI) per 100 person-years of benzodiazepine and Z-drug use stratified by cohort and (A) sex* and (B) age group*. *Numbers above columns represent ratios comparing MS and non-MS cohorts.
Figure 3
Figure 3
Prevalence (95% CI) of benzodiazepine and Z-drug use per 100 persons in MS and non-MS cohorts, stratified by (A) sex* and (B) age*. *Numbers above columns represent ratios comparing MS and non-MS cohorts.
Figure 4
Figure 4
Age- and sex-standardized* prevalence of (A) benzodiazepine and (B) Z-drug use stratified by cohort and mood/anxiety disorder. *To 2010 Canadian population.
Figure 5
Figure 5
Persistence on (A) Benzodiazepines and (B) Z-drugs according to multiple sclerosis (MS) and mood/anxiety disorder (MAD) status.
See this image and copyright information in PMC

References

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