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Dementia is a neurodegenerative disorder. There is no cure for this chronic and progressive condition, which impairs memory as well as judgment in function, in behaviour and language. A large amount of research into dementia is focused on the prevention of this condition rather than its cure. This article examines the link between antidepressants and the development of dementia.
How Do Antidepressants Work?
Antidepressants are used to help patients suffering from depression. Many different types of antidepressants have been developed. They are very similar in their mode of action; however, they differ in structure as well as in their adverse effects. Selective serotonin reuptake inhibitors (SSRIs) are one type of antidepressants. They block the reuptake of serotonin into the nerve cell and prolong its action within the brain. Serotonin and noradrenalin reuptake inhibitors (SNRIs) also inhibit the reuptake of serotonin but also that of noradrenalin, increasing the levels of both neurotransmitters over a longer duration in the brain. Another drug category is known as monoamine oxidase inhibitors (MAOIs); they also increase the duration of neuronal activation by serotonin and noradrenalin by making it harder for monoamine oxidase to break them down.
Antidepressants may affect the risk of dementia by their different mechanisms of action, which may include anticholinergic characteristics, cytotoxicity in many normal cells, neuron growth and death, some neurologic adverse effects and other symptoms.
Antidepressant Medications. Image Credit: Shidlovski / Shutterstock
Is There a Link Between Antidepressants and the Increased Risk of Dementia?
Some hypotheses do suggest a link between antidepressant intake and the risk of dementia. One theory is that antidepressants have anticholinergic characteristics; they can block acetylcholine action within the central or peripheral nervous system. As anticholinergic activity influences the cognitive function of patients, the use of these drugs is thought to increase the risk of dementia.
However, other studies suggest that antidepressants could have anti-inflammatory effects due to a different mode of action, such as modification of glial activation, which reduces the risk of dementia.
Studies on both hypotheses have been conducted. While some studies have shown no increased risk of dementia associated with antidepressants, other have reported both reduced and increased risk of dementia in patients taking antidepressants. The discrepancies in these studies might be due to the differences in the study types.
In many cases, older patients are treated with cocktails of drugs for various conditions. Some of these drugs have the same mode of action, which includes blocking the neurotransmitter acetylcholine. Antidepressants also share this mechanism of action. Such a massive blockade of acetylcholine could have an impact on the brain as regards cognition, memory and learning.
One study used data on over 40,000 people who were more than 65 years of age, and suffering from dementia, as well as 300,000 patients without dementia. Based on an analysis of the prescribed drugs, the scientists concluded that patients with a history of taking anticholinergic drugs between 4 and 20 years earlier were more likely to develop dementia. The risk of dementia was especially increased, from 10% to 13%, in patients who were on drugs for the treatment of depression, Parkinson’s disease, and bladder problems. Therefore, researchers have advised caution when prescribing these drugs. However, other scientists disagree with the study conclusion that these drugs increase dementia risk.
Dr. Parastou Donyai, associate professor of social and cognitive pharmacy at the University of Reading, is one of them. He states that this study only pointed out the increased risk of dementia linked to the regular use of antidepressants. He highlights the fact that many patients take their prescribed medication only half of the time or less, or not at all.
Another very recent study by Arad Kodesh,. et al., used data on over 75,000 patients aged 60 years and over to detect a link between an increased risk of dementia and antidepressant intake. However, the study failed to report any stratification of risk by specific drug or drug class, though others have shown that tricyclic antidepressants decrease the risk of dementia. Another recent meta-analysis reported an increased risk of developing dementia in older patients who take antidepressants as compared to patients who do not take any antidepressants. Furthermore, this study revealed that patients on monoamine oxidase inhibitor therapy had a higher risk of developing dementia compared with patients on tricyclic and selective serotonin reuptake inhibitors.
Take-Home Message
Controversy and tentativeness still mark the association of dementia risk and regular antidepressant use. Nonetheless, these study outcomes are important for healthcare providers to consider before starting patients with depression on antidepressants.
In any case, it is recommended that treatment with these types of drugs should be only for a short period of time, and with simultaneous monitoring for any symptoms related to dementia .
Anti-depressants are still widely prescribed drugs and are vital to maintain normal life quality in some patients. However, with no consensus on the risk of dementia with antidepressants, more large-scale studies over a longer term will be necessary. This will help answer which antidepressant can be linked to a higher risk of dementia.
Further Reading
Cryo-EM reveals TAF15 as potential treatment target for frontotemporal dementia