Improving the lives of patients with schizophrenia by managing anticholinergic burden

Mar 23, 2021

Dr. Tarek Rajji uncovers how a side-effect of medications used to treat schizophrenia can make daily life more challenging for those living with the mental illness, and what can be done to prevent it.

Medication can vastly improve the lives of people with schizophrenia, helping them manage symptoms and live more independently. But could some medications end up making day-to-day activities more difficult? Dr. Tarek Rajji and his team believe that understanding anticholinergic burden could be the key to making sure that medication is helping patients with schizophrenia, not harming them.




What is anticholinergic burden?

TR: Cholinergic receptors are structures in the brain and body that are critical for a variety of healthy functions, including memory and thinking processes. Some medications used to treat schizophrenia have the unwanted side effect of blocking these receptors, which can cause memory problems.

The degree to which a person’s cholinergic receptors are blocked is called their anticholinergic burden. Anticholinergic burden can impair their ability to perform day-to-day activities, e.g. calling a doctor to change their appointment; following a recipe to make a meal; using a map to go from point A to B; reading a bill and writing a cheque to pay. 

What motivated this research?

TR: People with schizophrenia often need to be on medications for long periods of time. Unfortunately, many of these medications can block the cholinergic receptors in the brain, creating a high anticholinergic burden.  Through experiments with “paper-and-pencil” tests, we know that this can cause memory and thinking problems. However, we don’t yet know whether high anticholinergic burden can also affect their ability to perform day-to-day activities. This is important because schizophrenia affects people’s abilities to live daily life on its own. Exposing these individuals to such a high anticholinergic burden could even have a more severe impact on their independence and quality of life.
What was the most important finding of this study, in your opinion?

TR: We found that high anticholinergic burdens could impair day-to-day activities in people with schizophrenia, independent of its negative impact on memory or thinking. Interestingly, in our study we also found that the negative impact on memory and thinking happened only in those aged 55 or older.

How does this change treatment of patients with schizophrenia?

TR: Our findings highlight the importance of carefully reviewing what medications to use for schizophrenia and, when possible, choosing medications that don’t cause high blockage of the cholinergic receptors. It is also important to have an ongoing review of medications, especially as people with schizophrenia grow older since blockage of cholinergic receptors seems to have the greatest impact on older individuals. This is crucial because older individuals with schizophrenia also have a higher risk of developing dementia, which itself causes impairments in day-to-day activities on top of schizophrenia and the anticholinergic burden.
Any next steps?

TR: One next step is to examine whether reducing anticholinergic burden by reducing the dose of medications or by switching medications can result in improvements in the day-to-day functioning of people with schizophrenia. Another next step would be to reduce anticholinergic burden in combination with treatments that could enhance memory, thinking, or function, because people may not experience the full benefits of these treatments if they are also being subjected to high anticholinergic burden.

What is the major take home message for the public?

TR: As patients, families and clinicians, we should always be mindful of the medications we are dealing with. 
In this case, we need to be aware of anticholinergic burden and the real-life impact it can have on patients’ ability to perform day-to-day activities. Anticholinergic burden must be managed if we are to provide patients with the best possible quality of life.  


Funded by Canadian Institutes of Health Research; US National Institutes of Health; and Centre for Addiction and Mental Health (CAMH) Discovery Fund.







ImPACT Committee includes Krista Lanctôt, Alastair Flint, Meng-Chuan Lai and Simone Vigod.

Khan WU, Ghazala Z, Brooks HJ, Subramaniam P, Mulsant BH, Kumar S, Voineskos AN, Blumberger DM, Kern RS, Rajji TK. The Impact of Anticholinergic Burden on Functional Capacity in Persons With Schizophrenia Across the Adult Life Span. Schizophr Bull. 2021 Jan 23;47(1):249-257. doi: 10.1093/schbul/sbaa093.