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Do antidepressant medications increase the risk of dementia in older adults?

What if you or one of your parents experience depression later in life, and the doctor prescribes an antidepressant? It’s important to understand the health risks and take careful steps to minimize them, especially if other medications are being taken as well. As we get older, medication management becomes trickier due to age-related slowing of metabolism, as well as potential interactions with drugs used to treat other chronic conditions such as blood pressure, cholesterol, diabetes and chronic pain. A person’s DNA also plays a vital role in medication response. A mismatch between a person’s genetic drug response profile and their antidepressant can lead to serious side effects, including dementia, drug-induced psychosis and other complications. Here we describe how pharmacogenetic testing, combined with a medication review by an expert pharmacist, can help to minimize the risk of antidepressant-induced side effects and dementia in older adults.

The prevalence of dementia

Dementia is a neurocognitive disorder that is characterized by irreversible cognitive decline. The disorder currently affects 5% to 6% of individuals older than the age of 60, but with an aging population, the prevalence is expected to double by 2040. Although there are medications to manage symptoms, there is no cure for dementia. As such, identifying risk factors that accelerate cognitive decline and lead to dementia can help delay its onset and reduce the risk of developing the condition.

Antidepressants and other medications may increase the risk of dementia

Late-life depression is a common condition affecting many individuals over the age of 55. Despite the limited effectiveness of antidepressants in the elderly, they are often prescribed for the treatment of depression. Studies have also shown a direct link between depression and antidepressant medications with the development of dementia. Many antidepressant medications act as anticholinergic drugs, which block acetylcholine, a natural neurotransmitter chemical in the brain. Anticholinergic drugs have broad effects on the brain and nervous system and are used in older adults to treat a multitude of conditions including asthma, COPD, urinary incontinence, and insomnia.

However, some antidepressants, and other anticholinergics, are known to cause confusion, memory loss, and declining cognitive function in individuals who are over the age of 65, which may increase the risk of developing dementia. Furthermore, a recent study showed that in older adults, reducing the use of anticholinergic medications by 20% can reduce the behavioural and psychological symptoms of dementia and burden on caregivers. As such, patients over 65 taking multiple medications are advised to get their medications reviewed by a pharmacist to reduce the anticholinergic burden.

Although most studies have shown an increased risk of dementia as a result of antidepressant usage, there are notable exceptions. Appropriately matched antidepressants can reduce the risk of dementia. Doctors have been advised to be vigilant in prescribing antidepressants to older adults, especially if the medication has a low probability of being successful. However, in practice, many patients are prescribed antidepressants and antipsychotic medications that are contraindicated for the elderly.

The importance of pharmacogenetic testing in managing depression and reducing risk for dementia

Clinical studies have shown that the prevalence of depression increases with age, particularly in individuals with chronic conditions. The majority of these individuals do not respond to initial antidepressant treatment, and consequently, have to try different medications and dosages to find what works best to alleviate depression symptoms. Pharmacogenetic analysis can guide antidepressant selection to help you find the right prescription sooner and reduce the occurrence of adverse events.

How does pharmacogenetics work?

More specifically, pharmacogenetic tests, such as Pillcheck, detect variations in genes (including two called CYP2D6 and CYP2C19). These genes determine the activity of enzymes responsible for metabolising antidepressants and other medications in the liver. When a variation of these genes causes an individual to be a poor metabolizer of an antidepressant, the drug will persist in the body for longer than intended and cause increased exposure and risk for adverse side effects.

Given the link between antidepressant exposure and dementia, the low success rate of antidepressants, and age-related lower metabolism rate, older adults using antidepressant medication are advised to get pharmacogenetic testing. The Pillcheck pharmacogenetic testing service provides doctors with important insights to help them prescribe medication and dosages that are most likely to manage depression symptoms safely and effectively. Pillcheck reports on over 200 drugs commonly used for mental health, gastrointestinal, cardiovascular, neurological, and chronic pain conditions. A Pillcheck pharmacist reviews each customer’s medications and evaluates prescription fit based on the individual’s drug metabolic profile, Beers Criteria (a list of potentially inappropriate medications for older persons) and other clinical factors. By enabling physicians to tailor drug selection and dosages to fit your age and genetic profile, Pillcheck helps to lower side effects and may reduce the risk of antidepressant-related dementia in older adults.


  • Risk of depression increases with age and is often managed using antidepressants, yet antidepressants can increase the risk of developing dementia
  • Response to antidepressants is impacted by age-related factors and an individual’s genetic profile
  • Pharmacogenetic tests, such as Pillcheck, can help to assess an individual’s ability to metabolize different drugs
  • Pharmacogenetics-based selection of antidepressant can reduce the risk of treatment failure in patients with depression and lower the risk of adverse side effects, such as the onset of dementia

Use Pillcheck’s DNA drug response testing to personalize your healthcare.

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Selected References

Kessing, L. V., Søndergård, L., Forman, J. L., & Andersen, P. K., Antidepressants and dementia Journal of Affective Disorders. 2009;117(1-2), 24–29.

Heser K, at al., Potentially inappropriate medication: Association between the use of antidepressant drugs and the subsequent risk for dementia Journal of Affective Disorders. 2018;226:28-35.

Kok RM, Reynolds CF. Management of Depression in Older Adults: A Review. JAMA. 2017;317(20):2114–2122.

Hicks JK, at al., Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors Clinical Phrmocology & Therapetuics. 2015;98(2):127-134

Kodesh A, et al., Exposure to Antidepressant Medication and the Risk of Incident Dementia. The American Journal of Geriatric Psychiatry. 2019;27(11):1177-1188.

Richardson K, et al., Anticholinergic Drugs and Risk of Dementia: Case-Control Study. BMJ. 2018;360:k1315.

Jaidi Y, et al., Reduction of the Anticholinergic Burden Makes It Possible to Decrease Behavioral and Psychological Symptoms of Dementia The American Journal of Geriatric Psychiatry. 2017;26(3):280-288

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