Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study.
OBJECTIVE
To investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD).


METHODS
The register-based MEDALZ cohort, including all community-dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register. To study new users, persons who had any BZDR use during the year preceding the AD diagnosis were excluded. For each person initiating BZDR use (n = 10 380), 2 nonusers (n = 20 760) were matched on age, gender, and time since AD diagnosis. The outcome was 180-day mortality, and BZDR use was compared with nonuse with Cox regression. Multivariable analyses were adjusted for Charlson comorbidity index, socioeconomic position, hip fractures, psychiatric disorders, substance abuse, stroke, and other psychotropic drug use.


RESULTS
During the follow-up, 5 excess deaths per 100 person-years occurred during BZDR use in comparison to nonuse, and mortality rates were 13.4 (95% confidence interval [CI], 12.2-14.5) and 8.5 (95% CI, 7.9-9.1), respectively. Benzodiazepine and related drug use was associated with an increased risk of death (adjusted hazard ratio = 1.4 [95% CI, 1.2-1.6]), and the association was significant from the initiation of use. Benzodiazepine use was associated with an increased risk of death, whereas benzodiazepine-related drug use was not.


CONCLUSIONS
Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first-line option for symptomatic treatment of AD.
['Saarelainen|Laura|L|0000-0003-2542-8137', 'Tolppanen|Anna-Maija|AM|', 'Koponen|Marjaana|M|', 'Tanskanen|Antti|A|', 'Tiihonen|Jari|J|', 'Hartikainen|Sirpa|S|', 'Taipale|Heidi|H|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D001569:Benzodiazepines D015331:Cohort Studies D005260:Female D005387:Finland D006620:Hip Fractures D006801:Humans D006993:Hypnotics and Sedatives D008297:Male D008875:Middle Aged D015999:Multivariate Analysis D016016:Proportional Hazards Models D012307:Risk Factors D020521:Stroke D019966:Substance-Related Disorders
benzodiazepines Alzheimer disease cohort study Prescription Register mortality drug safety