What are the potential side effects of Chlorpheniramin, especially in elderly patients with a history of dementia?

Chlorpheniramine Side Effects

Chlorpheniramine, a first-generation antihistamine, carries significant risks of sedation, cognitive decline, and anticholinergic toxicity—particularly dangerous in elderly patients with dementia who should avoid this medication whenever possible. 1

Central Nervous System Effects

Cognitive Impairment and Sedation

• Chlorpheniramine causes daytime drowsiness, impairs visuomotor coordination, and reduces the ability to detect auditory stimuli during sustained concentration tasks. 2
• The drug alters auditory attention systems, increases P300 latency (affecting voluntary stimulus discrimination), and reduces mismatch negativity amplitude (impairing automatic detection of environmental changes). 2
• Patients may not be subjectively aware of these cognitive impairments, making chlorpheniramine particularly dangerous in situations requiring alertness. 2
• Psychosis and cognitive changes occur more commonly in older persons taking first-generation antihistamines. 1

Specific Risks in Elderly Patients with Dementia

• First-generation H1 antihistamines including chlorpheniramine are associated with cognitive decline, particularly in elderly patients, and should be avoided in those with dementia. 1
• Strongly anticholinergic medications like chlorpheniramine are poorly tolerated in aged patients due to broad muscarinic receptor blockade affecting vision, urination, constipation, and cognition. 1
• The decline in acetylcholine physiology associated with aging is further compromised by anticholinergics, creating an "anticholinergic burden" that adversely affects cognition, functional status, and activities of daily living scores. 1

Anticholinergic Effects

Systemic Anticholinergic Toxicity

• Anticholinergic toxicity ranges from dry mouth, constipation, and visual impairments to confusion, delirium, and severe cognitive decline. 3
• The toxicity often results from cumulative anticholinergic burden of multiple medications rather than a single compound. 3
• Management of elderly patients, especially those with dementia, should aim to reduce medications with anticholinergic effects. 3

Specific Contraindications (FDA Label)

• Patients should consult a physician before use if they have glaucoma, urinary retention due to enlarged prostate, or breathing problems such as emphysema or chronic bronchitis. 4

Serious Safety Concerns

Fall Risk and Accidents

• Anticholinergic and sedating medications are associated with injurious falls, episodes of confusion or delirium, emergency department visits, and hospitalizations. 1
• Two autopsy cases documented accidental deaths in elderly individuals (both women in their 70s) under the influence of chlorpheniramine, with blood/fluid levels of 0.41 μg/mL and 0.57 μg/mL respectively. 5
• Antihistamine-induced drowsiness may compound accidental overdoses of cold medications containing chlorpheniramine. 5

Perioperative Considerations

Postoperative Delirium Risk

• Anticholinergic drugs including chlorpheniramine are strongly associated with increased postoperative delirium and should be avoided or discontinued perioperatively in older adults. 1
• Diphenhydramine (a related first-generation antihistamine) has been specifically identified as increasing delirium risk. 1

Drug Tolerance and Compliance Issues

Subsensitivity Development

• Patients develop true subsensitivity to chlorpheniramine during chronic therapy (3 weeks), with significantly reduced clinical effectiveness compared to short-term use. 6
• This subsensitivity is not explained by changes in drug metabolism but represents true pharmacodynamic tolerance. 6
• Poor compliance during chronic therapy may contribute to subtherapeutic results, compounded by persistent side effects (particularly drowsiness). 6

Clinical Recommendations

Deprescribing Priority

• Chlorpheniramine should be prioritized for deprescribing in older adults, especially those with cognitive impairment, as part of reducing high-risk medications. 1
• The liabilities associated with anticholinergic medications raise the cost of care through falls, confusion, emergency visits, and hospitalizations. 1

Alternative Considerations

• When antihistamine therapy is necessary, later-generation nonsedating H1 antihistamines such as fexofenadine and cetirizine are preferred, as they have lower anticholinergic effects and reduced cognitive impact. 1