Abstract
ObjectiveBenzodiazepines (BZD) are one of the most frequently prescribed drugs worldwide. However, the cognitive effects of benzodiazepines in the elderly are highly debated. This systematic review and meta-analysis aims to explore the following two questions in the elderly population: (i) Do BZD lead to any impairments in cognitive functions in elderly users? and (ii) Which specific cognitive domains are most affected by BZD use and abuse?MethodsFirst, we performed a literature search following the PRISMA guidelines. Electronic databases, including PubMed, PsycINFO, EMBASE, Cochrane Library, and Web of Science were searched until May 14th, 2020. After selecting the relevant articles, we integrated the results of the selected studies with a standardized cognitive classification method. Next, we performed meta-analyses with the random-effects model on the cognitive results. Finally, we specifically examined the cognitive impairments of BZD in the abuse subgroup.ResultsOf the included studies, eight of the thirteen had meta-analyzable data. Compared to the controls, elderly BZD users had significantly lower digital symbol test scores (n=253; SMD: -0.61, 95% CI: -0.91 to 0.31, I² = 0%, p < 0.0001). There was no significant difference in Mini-Mental State Examination, Auditory Verbal Learning Test, and Stroop Color and Word Test scores between BZD users and controls. According to the subgroup analyses, BZD abusers performed significantly worse than controls in Mini-Mental State Examination (n=7726; SMD: -0.23, 95% CI: -0.44 to -0.03, I² = 86%, p = 0.02), while there was no significant difference between the regular BZD users and the controls (n=1536; SMD: -0.05, 95% CI: -0.59 to 0.48, I² = 92%, p =0.85).ConclusionIn the elderly population, the processing speed (digital symbol test scores) was significantly impaired in BZD users; global cognition (Mini-Mental State Examination scores) was significantly impaired in BZD abusers but not in BZD regular users. This study provides insight into the factors that interact with BZD cognitive effects, such as aging, testing tools, and abuse. Clinicians should be cautious when prescribing BZD for the elderly.Systematic Review RegistrationPROSPERO, identifier CRD42019124711.
Highlights
Benzodiazepines (BZD) are two-ring heterocyclic compounds consisting of a benzene ring fused with a diazepine ring
The results showed that in the elderly, the BZD users performed significantly worse than controls in digit symbol tests (n=253; Standardized mean difference (SMD): -0.61, 95% confidence intervals (CIs): -0.91 to 0.31, I2 = 0%, p < 0.0001)
Consistent with previous systematic reviews, our meta-analysis suggests no impairment in global cognition among elderly BZD users (49, 50)
Summary
Benzodiazepines (BZD) are two-ring heterocyclic compounds consisting of a benzene ring fused with a diazepine ring. Since its discovery in the 1950s, BZD’s sedative, hypnotic, anti-anxiety, and anti-convulsive effects have been increasingly accepted, making BZD use highly prevalent among adults (1) and especially in the elders (2). The prevalence of BZD use in elders varies between 10% and 42% worldwide (3). Inappropriate BZD prescriptions can promote BZD misuse, facilitate the development of BZD addiction, and significantly affect the users’ overall quality of life (5, 6). It is critical for pharmacists, clinicians, and patients to be informed on the latest research regarding the adverse effects of BZD use and abuse
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