Can Cardizem (diltiazem) cause delirium in elderly patients?

Cardizem (Diltiazem) Can Cause Delirium in Elderly Patients

Yes, Cardizem (diltiazem) can cause delirium in elderly patients, particularly when used at higher doses or in patients with renal or hepatic impairment. This risk is documented in case reports and is consistent with the pharmacological properties of calcium channel blockers in older adults 1.

Mechanism and Risk Factors

Diltiazem can contribute to delirium through several mechanisms:

1. Pharmacokinetic changes in elderly patients:

   • Decreased hepatic metabolism and renal clearance leading to drug accumulation 2
   • Reduced protein binding resulting in higher free drug concentrations

2. Pharmacodynamic factors:

   • Age-related changes in cardiovascular structure and function that alter drug response 2
   • Increased sensitivity to central nervous system effects
   • Potential drug interactions, particularly with medications metabolized by CYP3A enzymes 1

3. Risk amplifiers:

   • Polypharmacy (common in elderly patients)
   • Underlying cognitive impairment
   • Dehydration
   • Renal or hepatic dysfunction

Evidence of Diltiazem-Induced Delirium

The association between diltiazem and delirium is supported by case reports:

• A 68-year-old man developed delirium, confusion, and agitation after starting diltiazem therapy, with symptoms resolving after discontinuation 1
• A 74-year-old man presented with mental confusion and slurred speech associated with diltiazem overdose 3

Management Recommendations

When prescribing diltiazem to elderly patients:

1. Dosing considerations:

   • Start with lower doses (180 mg/day has been identified as optimal in elderly patients) 4
   • Avoid rapid dose escalation
   • Monitor for side effects at each dose level before increasing

2. Monitoring:

   • Assess mental status regularly, particularly after initiating therapy or changing doses
   • Monitor renal and hepatic function
   • Watch for signs of delirium: confusion, disorientation, altered consciousness, attention deficits

3. If delirium occurs:

   • Consider discontinuing diltiazem or reducing the dose
   • Rule out other causes of delirium
   • Provide supportive care and reorientation strategies

Prevention Strategies

To minimize the risk of diltiazem-induced delirium:

• Avoid in high-risk patients when possible, especially those with:

  • History of delirium
  • Advanced age (>80 years)
  • Multiple comorbidities
  • Polypharmacy
  • Renal or hepatic impairment

• Consider alternatives when appropriate, such as dihydropyridine calcium channel blockers which may have less CNS penetration

• Review medication regimen to reduce overall anticholinergic burden and drug interactions

Clinical Implications

The 2019 American Geriatrics Society Beers Criteria® recommends using caution with nondihydropyridine calcium channel blockers like diltiazem in older adults due to the risk of adverse effects including bradycardia and syncope 2. While delirium is not specifically mentioned in relation to diltiazem in the Beers Criteria, the general recommendation to avoid medications that can induce delirium applies 2.

The risk of delirium appears to increase with higher doses of diltiazem, with one study noting adverse effects in 8 out of 12 elderly patients at the highest dose (360 mg/day) compared to only 1 patient at the lowest dose (180 mg/day) 4.

Common Pitfalls

• Failure to recognize delirium as a medication side effect, mistaking it for progression of underlying cognitive impairment
• Not adjusting doses appropriately for elderly patients
• Overlooking drug interactions that may increase diltiazem levels or enhance CNS effects
• Adding medications to treat delirium symptoms rather than identifying diltiazem as the potential cause

Remember that medications are one of the most common reversible causes of delirium in the elderly, and careful medication management is essential for prevention 5.