In the United States, more than 1 in 10 people use antidepressants, with usage rising as people age. The U.S. Centers for Disease Control and Prevention reports that around one in four women over 60 use some form of antidepressant. If you’re among those taking antidepressants, you’re likely aware of the different types available.
These include the commonly prescribed selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), and noradrenaline and specific serotonergic antidepressants (NASSAs). Older antidepressants, like tricyclic antidepressants, are less frequently prescribed due to their side effects and overdose risks.
Research indicates that the long-term use of tricyclic antidepressants, such as doxepin (Silenor), may be associated with dementia. Although doxepin is technically an antidepressant, it is also used to treat insomnia. A 2018 meta-analysis in Behavioural Neurology reviewed five studies, finding that individuals taking tricyclic antidepressants had double the risk of developing dementia. Those using SSRIs had a 75% increased risk. However, more information is needed to fully understand how tricyclic antidepressants might impact dementia risk.
Tricyclic Antidepressants Have Anticholinergic Effects
Tricyclic antidepressants are used to treat not only depression and insomnia but also obsessive-compulsive disorder, chronic pain, migraines, and bedwetting. In addition to side effects like blurred vision, weight gain, and a rapid heart rate, older adults are more likely to experience memory problems and confusion (per Harvard Medical School). Because of this, and the availability of newer medications like SSRIs and SNRIs, tricyclic antidepressants are used less frequently in older adults.
These medications have anticholinergic side effects, meaning they block a specific neurotransmitter that helps control muscle movement, memory, and other functions. Anticholinergic drugs are used to treat a range of conditions, including incontinence, asthma, Parkinson’s disease, and motion sickness. Antihistamines such as diphenhydramine (Benadryl) also have anticholinergic effects.
It may be these anticholinergic effects, rather than the antidepressant action itself, that are linked to dementia. A 2016 study in The American Journal of Geriatric Psychiatry looked at older adults with depression living in nursing homes. Those who took strong anticholinergic medications, including tricyclic antidepressants, had a 26% higher risk of developing dementia.
Consider the Anticholinergic Effect of Your Medications
If you take medication such as Benadryl for its antihistamine properties, you know that it may also make you drowsy. That effect will go away if you stop taking Benadryl. If an anticholinergic side effect of a tricyclic antidepressant is confusion and memory loss, it might be reasonable to assume that these symptoms will go away if you stop taking the drug. However, a 2015 study in JAMA Internal Medicine found that former users of anticholinergic medications had the same risk of dementia as current users.
Because anticholinergic medications are used to treat a wide variety of conditions, a 2020 review in Expert Opinion on Drug Safety recognized the considerable risk factor of dementia with these medications. To minimize this risk, it was suggested that medical professionals take a look at how much of an anticholinergic burden an older patient has before prescribing a new medication.
(Read what happens when you stop taking antidepressants.)
Every three years, the American Geriatrics Society updates a list of medications (called the Beers Criteria) that should be avoided or minimized due to possible risk for adults over 65. Drugs with strong anticholinergic properties, such as tricyclic antidepressants, first-generation antihistamines (like over-the-counter diphenhydramine and doxylamine), some antipsychotics, and certain bladder incontinence drugs are on this list. If your medication has anticholinergic effects, you shouldn’t stop taking it. Instead, consult with your doctor about alternative drugs.