What are the recommendations for managing an elderly patient with a history of seizures, Alzheimer's dementia, previous cerebrovascular accident (CVA), hypertension, chronic kidney disease (CKD), coronary artery disease (CAD), pancreatic cancer, gastroesophageal reflux disease (GERD), and other conditions, who has been taking lisinopril (Zestril), Plavix (clopidogrel), and aspirin, and has recently discontinued Keppra (levetiracetam) due to family request, with no seizure-like activity, behavioral disturbances, or changes in mental status since discontinuation, and whose blood pressure is managed with lisinopril HCTZ (hydrochlorothiazide)?

Management of Elderly Patient After Keppra Discontinuation

Primary Recommendation

Continue monitoring without restarting Keppra, as the patient has remained seizure-free since discontinuation and the risks of antiepileptic drugs in this complex elderly patient likely outweigh benefits. 1, 2, 3

Clinical Assessment and Monitoring Strategy

Immediate Post-Discontinuation Evaluation

• Document the seizure-free period carefully, noting the exact duration since Keppra discontinuation and any subtle neurological changes that family may have missed, as seizures in dementia patients can be mistaken for behavioral symptoms of the underlying disease 2

• Verify that the patient truly had epilepsy requiring treatment, as the indication for Keppra initiation should be reviewed—treatment after a first seizure is only strongly indicated if there is evidence of focal neurological involvement or high risk of recurrence 2

• Monitor for at least 3-6 months post-discontinuation before considering the taper successful, as seizures in Alzheimer's disease typically occur in later stages (>6 years into disease course) and may have variable recurrence patterns 2

Blood Pressure Management Considerations

• The current lisinopril-HCTZ regimen should be optimized before considering additional agents, targeting <140/90 mmHg minimum (or <130/80 mmHg if tolerated) given the patient's multiple cardiovascular risk factors including previous CVA, CAD, and CKD 4, 5

• If blood pressure remains uncontrolled on lisinopril-HCTZ, add amlodipine 5-10mg daily as the third agent, creating the guideline-recommended triple therapy combination of ACE inhibitor + thiazide diuretic + calcium channel blocker 5, 6

• Monitor renal function closely when adjusting antihypertensives in this patient with CKD, checking serum creatinine and potassium 2-4 weeks after any medication change 4, 5

Antiplatelet Therapy Review

• The combination of Plavix (clopidogrel) and aspirin increases bleeding risk significantly, particularly in elderly patients, and should only be continued if there is a compelling indication such as recent acute coronary syndrome or coronary stenting within the past year 4

• Consider discontinuing aspirin if the patient is >1 year post-CVA and maintaining clopidogrel monotherapy, as dual antiplatelet therapy beyond 1 year post-stroke increases bleeding risk without proven additional benefit in most cases 4

Seizure Management Considerations

If Seizures Recur

• Restart levetiracetam at a low dose (500mg twice daily) if seizures recur, as it has favorable pharmacokinetics in elderly patients, minimal drug interactions with the current medication regimen (lisinopril, Plavix, aspirin), and superior cognitive tolerability compared to traditional antiepileptic drugs 7, 3

• Levetiracetam demonstrated significant cognitive improvements in elderly patients with dementia in a 12-week study, with 69% achieving seizure freedom and improvements in Mini-Mental State Examination scores, making it the preferred agent if treatment becomes necessary 3

• Alternative agents if levetiracetam is not tolerated include lamotrigine or gabapentin, both of which have minimal cognitive adverse effects suitable for dementia patients, though lamotrigine requires slow titration 2

Reasons Supporting Continued Observation

• The patient has remained stable without seizure-like activity, behavioral disturbances, or mental status changes since discontinuation, suggesting that either the original seizure diagnosis was questionable or the seizure disorder has resolved 1, 2

• Antiepileptic drugs carry significant risks in elderly patients with dementia, including cognitive slowing, sedation, behavioral changes, and increased fall risk—all of which could worsen quality of life and functional status 2, 8, 3

• Levetiracetam can cause behavioral side effects including aggression, agitation, irritability, and depression, which are particularly problematic in patients with Alzheimer's dementia who already have behavioral disturbances 1

Critical Medication Management Issues

Polypharmacy Concerns

• This patient is at high risk for medication non-adherence due to cognitive impairment, and reducing medication burden by keeping Keppra discontinued (if clinically appropriate) may improve adherence to essential cardiovascular medications 8

• Cognitive impairment substantially compromises medication adherence behavior, and patients with impaired executive function and lack of illness awareness are at particular risk of non-adherence 8

• Consider medication organizers or caregiver supervision for all medications given the dementia diagnosis, as performance-based assessments of medication management capacity should be conducted when cognitive impairment impacts medication self-management 8

Drug Interaction Considerations

• Levetiracetam has no significant drug interactions with lisinopril, Plavix, or aspirin, making it the safest antiepileptic choice if treatment becomes necessary, as it does not affect cytochrome P450 enzymes or protein binding 1

• Avoid enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin) in this patient, as they would accelerate metabolism of Plavix (reducing its antiplatelet efficacy) and potentially worsen cardiovascular disease through hyperlipidemia 7

Monitoring Parameters Going Forward

Neurological Monitoring

• Family should be educated to recognize seizure manifestations, including staring spells, confusion, automatisms, or any sudden behavioral changes, as seizures in dementia patients may be subtle and mistaken for dementia symptoms 2

• Schedule follow-up every 3 months initially, then every 6 months if the patient remains seizure-free, to assess for seizure recurrence and overall neurological status 2

Cardiovascular and Renal Monitoring

• Check blood pressure at each visit, with home blood pressure monitoring recommended to confirm control and detect white-coat or masked hypertension 4

• Monitor renal function (creatinine, eGFR) and electrolytes every 3-6 months given CKD and use of ACE inhibitor plus thiazide diuretic 4

• Assess for orthostatic hypotension at each visit by measuring blood pressure after 5 minutes sitting/lying and then 1-3 minutes after standing, as elderly patients with multiple antihypertensives are at high risk 4

Important Caveats

• Do not restart Keppra prophylactically without documented seizure recurrence, as the risks of antiepileptic drug therapy in this elderly patient with multiple comorbidities outweigh potential benefits when seizure-free 2, 3

• If the patient develops new unresponsiveness or altered mental status, consider causes other than seizures first, including medication effects, metabolic derangements, infection, or stroke progression, before attributing symptoms to seizure recurrence 2

• The pancreatic cancer diagnosis may impact overall prognosis and treatment goals, and aggressive seizure prophylaxis may not align with the patient's goals of care if life expectancy is limited—this should be discussed with the family 4