Is Long-Term Benzodiazepine Use a Risk Factor for Cognitive Decline? Results of a Systematic Review.

BACKGROUND AND AIMS: Benzodiazepines have been widely used for long periods of time despite their adverse effects. The acute effects on cognition are well established. However, less is known about the long-term effects. This study critically reviewed existing evidence of the association between long-term exposure to benzodiazepines and risk of cognitive decline in adults.

METHODS: A systematic review with narrative synthesis was conducted. PubMed and PsycINFO databases were searched using combinations of keywords related to "benzodiazepines" and "cognitive function" from database inception to 12 February 2018 to identify prospective longitudinal studies. The records were evaluated for relevance according to the inclusion and exclusion criteria.

RESULTS: Fourteen studies involving 2145 long-term benzodiazepine users were included. Meta-analysis was not undertaken because the combined result would not be meaningful as the included studies differed in several key aspects such as frequency and duration of benzodiazepine use, follow-up periods, cognitive domains, cognitive tests, scoring systems, and statistical analysis. The definition of long-term benzodiazepine use was problematic in all the studies. The exposure was determined by measures which were assumed to represent the whole period in-between the follow-ups. Only 3 of the 14 studies provided support for an association between long-term benzodiazepine use and cognitive decline with a small to medium effect size. However, these three studies used different methods to assess the strength of this association. Global cognitive functioning, verbal memory, intelligence, psychomotor speed, and speed of processing were the cognitive domains affected which also varied across these three studies.

CONCLUSIONS: Little evidence of an association between long-term benzodiazepine use and a higher risk of cognitive decline among the general adult population was found. However, discrepancies among the results and inconsistencies regarding the cognitive domains affected and methodological limitations prevent definite conclusions. Therefore, future research with prospective studies specially designed would be of great value.