Antihistamines, part II: Long-term adverse effects?

Additional recent studies have evaluated a potential risk for dementia with anticholinergic drugs. Richardson and colleagues identified the association between anticholinergic drugs and dementia in a case-control study. Patients aged 65 to 99 years with a diagnosis of dementia (n = 40,770) enrolled in a research database in England were compared with 283,933 controls without dementia. The researchers evaluated drugs recognized for having anticholinergic actions that were prescribed 4 to 20 years before a diagnosis of dementia. The adjusted OR for any drug with “definite anticholinergic activity” was 1.11 (95% CI, 1.08-1.14). In terms of drug classes, the researchers found a significant association between dementia and antidepressant, antiparkinson and urologic drugs. They found no association between dementia and antispasmodic, antipsychotic or antihistamine drugs.

Gray and colleagues evaluated 3,434 individuals aged 65 years and older in a prospective population-based cohort study. The participants, who did not have a diagnosis of dementia at study entry, were followed for a mean of 7.3 years. The most commonly used drug classes with anticholinergic actions included tricyclic antidepressants, antihistamines and bladder antimuscarinics. The researchers found that higher cumulative anticholinergic drug exposure was associated with dementia.

The conclusion of this month’s Pharmacology Consult column is not to infer that the use of first-generation antihistamines in the pediatric population will result in dementia as these children age into adulthood. Data from the adult studies described earlier have not definitively proven this risk, although an association between the use of drugs with anticholinergic actions and an increasing risk for dementia has been demonstrated. It is encouraging that a specific association between the use of antihistamines and dementia was not demonstrated in several of these studies, although the additional use of OTC antihistamine drugs may not have been fully evaluated. Experts have suggested that prospective controlled trials (“deprescribing” drugs) are needed to further define the potential for permanent negative cognitive effects of drugs with anticholinergic actions. Although it is known that drugs with anticholinergic actions, such as first-generation antihistamines, impair cognition in children and adults, the duration and reversibility of these effects is not well known. Animal and pathologic studies have shown that drugs with anticholinergic activity display neurodegenerative effects. The clinical implications for adverse cognitive changes are thus concerning. Perhaps the summary conclusion for this month’s column — as well as September’s column — is one that has been repeated in many of the Pharmacology Consult columns over the past 20 years: When considering the use of any medication, the balance between drug benefit and risk must be assessed. If evidence for a drug’s therapeutic benefit does not exist, it is best not given. Prescribers and patients alike must always weigh the potential for adverse effects that all drugs possess.


Campbell NL, Boustani MA. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2014.7667.

Campbell NL, et al. JAMA Intern Med. 2019;doi:10.1001/jamainternmed.2019.0676.

Coupland CA, et al. JAMA Intern Med. 2019;doi:10.1001/jamaintermed.2019.0677.

Gray SL, et al. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2014.7663.

Richardson K, et al. BMJ. 2018;doi:10.1136/bmj.k1315.

Ten Eick AP, et al. Drug Safety. 2001;doi:10.2165/00002018-200124020-00003.

For more information:

Edward A. Bell, PharmD, BCPS, is a professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences and Blank Children’s Hospital and Clinics in Des Moines, Iowa. He also is a member of the Infectious Diseases in Children Editorial Board. Bell can be reached at [email protected]

Disclosure: Bell reports no relevant financial disclosures.

This content was originally published here.

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