Atypical Antipsychotics and Parkinsonism

Rochon, Paula A.; Stukel, Thérèse A.; Sykora, Kathy; Gill, Sudeep S.; Garfinkel, Susan; Anderson, Geoffrey M.; Normand, Sharon‐Lise T.; Mamdani, Muhammad; Lee, Philip E.; Li, Ping; Bronskill, Susan E.; Marras, Connie; Gurwitz, Jerry H.

doi:10.1001/archinte.165.16.1882

Cited by 148 publications

(114 citation statements)

References 17 publications

(16 reference statements)

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“…A 30-year population-based study indicated that DIP is the fifth most common cause of Parkinsonism [21]. Several previous studies have investigated DIP caused by antipsychotics [21,22], calcium channel blockers [17], and antiemetics [23]. Although DIP has been reported in patients treated with TMZ [10,11], little is known about the risk of Parkinsonism induced by TMZ.…”

Section: Discussionmentioning

confidence: 99%

Association between Trimetazidine and Parkinsonism: A Population-Based Study

Kwon

Kim

et al. 2019

Neuroepidemiology

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Background: The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. Objectives: To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. Methods: A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. Results: Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06–1.81; p = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13– 3.74; p = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87–5.61; p < 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. Conclusions: Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.

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Section: Discussionmentioning

confidence: 99%

Association between Trimetazidine and Parkinsonism: A Population-Based Study

Kwon

Kim

et al. 2019

Neuroepidemiology

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“…Acute care hospital admissions were divided into 2 categories: known serious events (ie, EPS, falls or hip fractures, and cerebrovascular events) or other events. The EPS, including parkinsonism 3 and other druginduced movement disorders, 2 as well as falls 4 20 We defined other hospital admissions as acute care hospital admissions that were not for one of these known events.…”

Section: Data Management: Definitions and Standards For Expedited Repmentioning

confidence: 99%

Antipsychotic Therapy and Short-term Serious Events in Older Adults With Dementia

Rochon¹

2008

Arch Intern Med

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211

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Background: Antipsychotic therapy is widely used to treat behavioral problems in older adults with dementia. Cohort studies evaluating the safety of antipsychotic therapy generally focus on a single adverse event. We compared the rate of developing any serious event, a composite outcome defined as an event serious enough to lead to an acute care hospital admission or death within 30 days of initiating antipsychotic therapy, to better estimate the overall burden of short-term harm associated with these agents. Methods:In this population-based, retrospective cohort study, we identified 20 682 matched older adults with dementia living in the community and 20 559 matched individuals living in a nursing home between April 1, 1997, and March 31, 2004. Propensity-based matching was used to balance differences between the drug exposure groups in each setting. To examine the effects of antipsychotic drug use on the composite outcome of any serious event we used a conditional logistic regression model. We also estimated adjusted odds ratios using mod-els that included all covariates with a standard difference greater than 0.10.Results: Relative to those who received no antipsychotic therapy, community-dwelling older adults newly dispensed an atypical antipsychotic therapy were 3.2 times more likely (95% confidence interval, 2.77-3.68) and those who received conventional antipsychotic therapy were 3.8 times more likely (95% confidence interval, 3.31-4.39) to develop any serious event during the 30 days of follow-up. The pattern of serious events was similar but less pronounced among older adults living in a nursing home.Conclusions: Serious events, as indicated by a hospital admission or death, are frequent following the shortterm use of antipsychotic drugs in older adults with dementia. Antipsychotic drugs should be used with caution even when short-term therapy is being prescribed.

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“…While Health Canada warnings for increased rates of cerebrovascular adverse events and mortality based on the RCTs of the atypical antipsychotics had already been published at the time of the third CCCDTD and were carefully considered, subsequent RCTs and data from large administrative health databases raise further concerns about the safety of the antipsychotics in older dementia patients. Th ese concerns include cognitive decline [89], adverse metabolic eff ects [90,91], and extrapyramidal symptoms [92]. Similarly, newer studies appear to confi rm the risk of excess mortality in antipsychotic-treated patients with dementia, although diff erent antipsychotics may have relatively diff erent risks and some other nonantipsychotic drugs may carry similar risks [93][94][95][96].…”

Section: Rationalementioning

confidence: 99%