Benadryl (Diphenhydramine) Should Be Avoided in Parkinson's Disease Patients
Diphenhydramine is not helpful for Parkinson's disease and should be avoided due to its strong anticholinergic effects that can worsen cognitive function, increase fall risk, and potentially exacerbate motor symptoms.
Why Diphenhydramine Is Harmful in Parkinson's Disease
Anticholinergic Burden and Cognitive Decline
- Diphenhydramine is classified as a strongly anticholinergic medication that is poorly tolerated in older patients and those with Parkinson's disease 1
- The anticholinergic effects cause broad muscarinic receptor blockade, resulting in negative effects on vision, urination, constipation, and cognition 1
- Patients taking anticholinergic drugs experience "anticholinergic burden" that adversely affects cognition, functional status, and activities of daily living (ADL) scores 1
- Even in younger Parkinson's disease patients (mean age 56.9 years), anticholinergic burden with scores >3 was independently associated with cognitive impairment (Odds Ratio: 2.55) 2
Increased Risk of Falls and Fractures
- Anticholinergic medications are associated with injurious falls, episodes of confusion or delirium, emergency department visits, and hospitalizations 1
- In hospitalized Parkinson's disease patients, those with the greatest anticholinergic burden (score ≥4) were 56% more likely to be diagnosed with fractures (adjusted odds ratio: 1.56) 3
Freezing of Gait
- Higher anticholinergic burden is independently associated with freezing of gait in Parkinson's disease patients (Odds Ratio: 3.19 for patient-reported measures and 2.41 for objective measures) 2
Delirium Risk
- Parkinson's disease inpatients with the greatest anticholinergic burden were 61% more likely to be diagnosed with delirium (adjusted odds ratio: 1.61) 3
Historical Context vs. Current Evidence
While a 1950 study mentioned Benadryl as "valuable addition" for older Parkinson's patients 4, this predates modern understanding of anticholinergic burden and was based on anecdotal experience rather than controlled studies. Current evidence overwhelmingly demonstrates harm from anticholinergic medications in Parkinson's disease.
Specific Recommendations for Medication Management
What to Avoid
- Anticholinergic medications should be discontinued in Parkinson's disease patients, especially those with cognitive decline 5
- For older Parkinson's patients (60 years and over), anticholinergic agents should be avoided because of their CNS effects 6
- Diphenhydramine should be used with caution in older adults, those with glaucoma, benign prostatic hypertrophy, ischemic heart disease, or hypertension 1
Alternative Approaches
- For sleep disorders in Parkinson's disease caused by nocturnal akinesia, controlled-release levodopa at bedtime is preferred over sedating antihistamines 5
- For psychosis in Parkinson's disease patients, quetiapine, clozapine, or pimavanserin are recommended alternatives, not anticholinergic agents 7
- For cognitive decline with psychosis, rivastigmine (a cholinesterase inhibitor) may be considered 8
Clinical Pitfalls to Avoid
- Do not prescribe diphenhydramine for sleep, anxiety, or any other indication in Parkinson's disease patients - the anticholinergic burden outweighs any potential benefit
- Be aware that 57.8% of Parkinson's disease inpatients are prescribed non-PD medications with moderate to very strong anticholinergic potential 3
- Review all medications for anticholinergic burden using standardized scales (Anticholinergic Cognitive Burden scale or Anticholinergic Risk Scale) 1, 2
- The cognitive and motor effects of anticholinergics occur even in younger Parkinson's patients, not just the elderly 2