Anticholinergic and Dopaminergic Medications Associated with Behavioral Disinhibition

Anticholinergic Medications

The American Geriatrics Society recommends avoiding anticholinergic medications, such as diphenhydramine, cyclobenzaprine, and oxybutynin, in older adults due to their strong anticholinergic effects, which can cause sedation, confusion, and episodes of delirium, and are associated with injurious falls, emergency department visits, and hospitalizations 1, 2
The American Geriatrics Society identifies prochlorperazine and promethazine as antiemetics that should be avoided in older adults due to their high anticholinergic properties 3
Tricyclic antidepressants and paroxetine have high anticholinergic properties that can induce delirium, according to the American Geriatrics Society 3
Histamine2-receptor antagonists, such as cimetidine, are associated with increased postoperative delirium, as reported by the American Geriatrics Society 3
Patients taking multiple anticholinergic drugs experience "anticholinergic burden" that adversely affects cognition, functional status, and activities of daily living scores, with a strength of evidence rated as high 1, 2
Anticholinergic drugs can cause paradoxical behavioral disinhibition, especially in younger children and those with developmental disabilities, with a moderate strength of evidence 4

Antipsychotics, such as dopamine antagonists, are used to treat agitation but can themselves cause behavioral changes and should be used cautiously, according to the American Academy of Child and Adolescent Psychiatry 5, 4, 6

The American Geriatrics Society recommends avoiding medications with high anticholinergic activity, such as meperidine, midazolam, and drugs contributing to serotonin syndrome, due to their increased risk of delirium 3

Paroxetine (selective serotonin reuptake inhibitor) shows high anticholinergic activity, measured at 5–15 pmol/mL atropine equivalents at typical therapeutic doses. 7
Cyproheptadine (first‑generation antihistamine) has extended anticholinergic activity together with antiserotonergic effects, making it particularly problematic. 7

First‑generation antihistamines cross the blood‑brain barrier and antagonize central H1 histaminergic and M1 muscarinic receptors, explaining their greater effectiveness for rhinorrhea but also their higher risk of central side effects. 8
Bedtime‑only dosing does not eliminate the anticholinergic effects of first‑generation antihistamines because of their prolonged plasma half‑life and the presence of active metabolites. 9
Concurrent use of first‑generation antihistamines with other CNS‑active substances (e.g., alcohol, sedatives) further enhances performance impairment. 9

Older adults are especially vulnerable to anticholinergic adverse effects due to age‑related decline in baseline cholinergic function and common comorbidities, resulting in impaired cognition, functional status, and activities of daily living. 9
In patients with advanced cancer, polypharmacy is associated with increased anticholinergic burden, reflecting greater use of anticholinergic agents for symptom control. 10