Electronic Thesis and Dissertation Repository

Thesis Format

Alternative Format

Degree

Master of Science

Program

Surgery

Supervisor

Welk, Blayne

2nd Supervisor

Chou, Queena

Co-Supervisor

Abstract

ABSTRACT

Objective

To determine if there is an increased risk of delirium among patients with overactive bladder (OAB) started on anticholinergic medication compared to beta-3 agonist.

Methods

We conducted a population-based, retrospective, matched weight cohort study using administrative data from Ontario, Canada from January 2016 until March 2020. We matched 13865 new users of Oxybutynin to 33097 new users of newer anticholinergic medications (Solifenacin, Tolterodine, Trospium, Darifenacin and Fesoterodine), and to 56062 new users of beta-3 agonist medication (Mirabegron); all of the included medications are only for the treatment of OAB. Matching weights (an extension of the propensity score weighting) were used to balance the three exposure groups based on 83 measured indicators of baseline health, comorbidity, medication usage and health care utilization. The primary exposure was the class of OAB medication (Oxybutynin, Newer anticholinergics, and Beta-3 agonist). The primary outcome was delirium using a validated administrative data definition. Logistic regression, and proportional hazards analysis were used to assess outcomes at 30 days, and during continuous use of the medications.

Results

The median (IQR) duration of continuous usage was 113 (30-380) days for Beta-3 agonist, 30 (28-72) days for Oxybutynin, and 62 (30-239) days for the newer anticholinergics. There was no increased risk of delirium in primary analysis among Oxybutynin and newer anticholinergics drug users compared to beta-3 agonist at the 30 days observational window (odds ratio 1.28, 95% CI 0.84-1.96, p=0.25 for Oxybutynin and OR 0.92, 95% CI 0.58-1.46, p=0.73 for newer anticholinergics). The secondary analysis accounting for the period of continuous use showed a small but significant increased risk of delirium with the use of newer anticholinergics drugs compared to beta-3 agonist (HR 1.13, 95% CI 1.02-1.26 for newer anticholinergics).

Conclusions

The use of anticholinergic medications among patients with OAB was not associated with increased risk of delirium compared to beta-3 agonist users at 30 days; however, the risk might be slightly increased with continuous usage of newer anticholinergic medications.

Keywords

Overactive Bladder, Delirium, Anticholinergics, Population-based.

Summary for Lay Audience

Summary for Lay Audience

Overactive bladder (urgency with or without incontinence, frequency and nocturia) is a common condition in 10-15% of the population with many bladder medications being used to control this condition. These medications act on the action of a brain chemical know as Acetylcholine where recent studies suggest long term use may cause cognitive decline and dementia. Annually, 25,000 Canadians are diagnosed with dementia with an annual cost of over $12 billion spent to care for those living with dementia.

The currently approved anticholinergic medications used in Canada can be divided into two main categories: (1) Oxybutynin (the first medication approved for OAB in the 1970’s); and (2) more recent medications (Tolterodine, Solifenacin, Darifenacin, Fesoterodine and Trospium).

The ODPRN (Ontario Drug Policy Research Network) final consolidation report from March 2016 recommended Oxybuytnin as the initial treatment for patients with overactive bladder syndrome while reserving the newer medications for intolerance or failure of Oxybutynin, requiring a limited use code for coverage by the Ontario Drug Plan. Despite this, Solifenacin continues to still be available only under a limited use code and Oxybutynin continues to be the sole first-line treatment option available on this plan.

This policy may be depriving people from medication that might be better tolerated, equally or more effective, and possibly more safe than Oxybutynin, a very old overactive bladder agent, which has clearly been associated with dementia and cognitive impairment versus newer drugs like Fesoterodine or Mirabegron.

Older Overactive bladder medications are linked to new onset of dementia as well as same case reports reporting delirium associated with anticholinergics, we conducted this study to assess the actual risk of delirium and to see if this can change the policy of general OAB drug use implemented by Ontario Drug Benefit. We did not demonstrate a risk of delirium associated with anticholinergics compared to the only beta-3 agonist ( Mirabegron, Uses a different receptor) in the 30 days period, however on extended analysis it showed an increased risk which is based on longer duration of use and dosage.

We still believe that anticholinergics should be used with caution in elderly people and those with underlying risk of delirium.

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