Which is less deliriogenic, Cogentin (benztropine) or Benadryl (diphenhydramine)?

Cogentin vs. Benadryl for Delirium Risk

Benadryl (diphenhydramine) is significantly more deliriogenic than Cogentin (benztropine), and both should be avoided when possible in patients at risk for delirium.

Deliriogenic Properties of Both Medications

Benadryl (Diphenhydramine)

• Specifically identified in guidelines as a high-risk medication for delirium
• The American Geriatrics Society guidelines explicitly list diphenhydramine among medications that should be avoided to prevent delirium 1
• Has strong anticholinergic properties that directly contribute to delirium risk
• Associated with acute delirium with hallucinations as documented in case reports 2
• Commonly implicated in delirium cases among hospitalized older adults 3

Cogentin (Benztropine)

• Also has anticholinergic properties that can induce delirium
• Case reports document delirium occurring 1-2 days after starting benztropine at standard doses (2mg twice daily) 4
• Guidelines specifically warn against using benztropine for managing extrapyramidal symptoms in patients with Alzheimer's disease 1
• Risk increases when combined with other medications like SSRIs 5

Clinical Decision-Making Algorithm

1. First consideration: Avoid both medications if possible

   • Both medications have anticholinergic properties that can induce delirium
   • Consider alternative approaches for the clinical indication

2. If medication is absolutely necessary:

   • Choose Cogentin over Benadryl when treating extrapyramidal symptoms
   • Consider lower doses of either medication to minimize delirium risk
   • Monitor closely for signs of delirium, especially in high-risk patients

3. High-risk patient factors to consider:

   • Advanced age (>65 years)
   • Pre-existing cognitive impairment
   • Multiple medications (especially those with anticholinergic properties)
   • Current acute illness or metabolic disturbances
   • History of delirium

Alternative Approaches

For Extrapyramidal Symptoms:

• Consider atypical antipsychotics which have lower risk of extrapyramidal symptoms
• Low-dose diazepam may be effective for some extrapyramidal symptoms when benztropine and diphenhydramine are contraindicated 6
• For patients with Alzheimer's disease requiring antipsychotics, avoid using benztropine or trihexyphenidyl for extrapyramidal symptoms 1

For Allergic Reactions:

• Consider non-sedating antihistamines with lower anticholinergic burden
• Reserve diphenhydramine for severe allergic or transfusion reactions only 1

Important Caveats and Monitoring

• The risk of delirium with either medication increases with:

  • Higher doses
  • Longer duration of use
  • Combination with other anticholinergic or CNS-active medications
  • Underlying risk factors for delirium

• If either medication must be used, implement non-pharmacological delirium prevention strategies:

  • Frequent reorientation
  • Maintaining sleep-wake cycles
  • Early mobilization
  • Ensuring sensory aids (glasses, hearing aids) are available 7

• Monitor for early signs of delirium using validated tools like the Confusion Assessment Method (CAM) 7

• Discontinue the medication immediately if signs of delirium develop

While both medications carry delirium risk due to their anticholinergic properties, diphenhydramine (Benadryl) is more prominently identified in guidelines as a medication to avoid for delirium prevention, making it likely the more deliriogenic of the two options.