What should be done for an adult with a history of cognitive decline, anxiety, and depression who is now having seizures?

Management of New-Onset Seizures in Adults with Cognitive Decline, Anxiety, and Depression

Immediate Seizure Management

For active seizures lasting >5 minutes, administer IV benzodiazepines (lorazepam preferred over diazepam if available), followed by second-line agents (fosphenytoin, levetiracetam, or valproic acid) if seizures persist despite optimal benzodiazepine dosing. 1, 2

• If IV access is unavailable, rectal diazepam should be administered unless medically or socially contraindicated 1
• All three second-line agents (fosphenytoin, levetiracetam, valproic acid) have similar efficacy (45-47%) for seizure cessation within 60 minutes 2

Critical Diagnostic Evaluation

The priority is identifying and treating underlying metabolic or structural causes rather than reflexively starting long-term antiseizure medications. 1, 2

Essential Workup for Provoked Seizures

• Check serum glucose, sodium, calcium, magnesium, and renal function immediately - electrolyte abnormalities (particularly hyponatremia and hypocalcemia) are significant seizure triggers that require correction rather than chronic antiseizure therapy 2
• Review all medications for seizure threshold-lowering drugs (tramadol, SSRIs including vilazodone) 2
• Obtain detailed substance use history including alcohol, as withdrawal seizures should be a diagnosis of exclusion, especially in first-time presentations 2, 3
• Assess medication compliance if the patient has known epilepsy - non-compliance is a major seizure precipitant 2

Neuroimaging and EEG Considerations

• Brain MRI is indicated for new-onset seizures in adults with cognitive decline to evaluate for structural lesions, stroke, or other CNS pathology 1, 3
• EEG should be performed if there is suspicion of ongoing seizure activity or to classify seizure type 4

Decision to Initiate Antiseizure Medications

Antiepileptic drugs should NOT be routinely prescribed after a first unprovoked seizure in adults who have returned to baseline. 1

When to START Long-Term Therapy

• If seizures are provoked by a correctable metabolic cause (hypocalcemia, hyponatremia, hypoglycemia), correct the underlying abnormality and use only temporary seizure control with short-acting medications if necessary - do not start chronic antiseizure drugs 2
• Long-term therapy is appropriate for recurrent unprovoked seizures (epilepsy diagnosis) or when risk factors for recurrence are high 1

When to AVOID Starting Therapy

• Single, self-limiting first seizures that have returned to baseline 1
• Seizures occurring within 7 days of acute metabolic, toxic, or systemic insult (provoked seizures) 1, 2
• Alcohol withdrawal seizures after the acute period has resolved 2, 3

Antiseizure Medication Selection in This Population

If chronic therapy is indicated, levetiracetam is preferred over older agents in patients with cognitive decline, anxiety, and depression due to lower risk of cognitive side effects and drug interactions. 1, 5, 6

Medication Considerations

• Avoid valproic acid in this population - while effective, it has higher risk of cognitive and behavioral side effects 1
• Phenobarbital and phenytoin carry higher risk of behavioral adverse effects and should be avoided when alternatives are available, particularly in patients with pre-existing cognitive dysfunction 1
• Carbamazepine is appropriate for partial onset seizures but has more drug interactions than levetiracetam 1

Important Caveats About Levetiracetam

• Levetiracetam can worsen psychiatric symptoms - 13.3% of patients experience behavioral symptoms (aggression, agitation, anxiety, depression, irritability) compared to 6.2% on placebo 5
• Monitor closely for emergence of suicidal thoughts, worsening depression, or behavioral changes, particularly in the first 4 weeks 5
• Psychotic symptoms occurred in 0.7% of treated patients, typically within the first week 5
• Despite these risks, recent evidence shows that AEDs are not independently associated with cognitive dysfunction beyond seizure frequency and mood symptoms 6

Addressing the Underlying Cognitive and Psychiatric Comorbidities

Cognitive dysfunction, anxiety, and depression are often primary features of epilepsy present from disease onset, not solely consequences of seizures or medications. 7, 8, 9

• Cognitive impairment is documented in 76% of patients with seizure recurrence and 55% without recurrence, with executive function and memory most affected 9
• Depression and anxiety are significant predictors of subjective cognitive dysfunction and should be treated concurrently 6
• Optimizing seizure control is the most important factor for cognitive outcomes - seizure frequency is a major predictor of objective cognitive dysfunction 6

Common Pitfalls to Avoid

• Do not overlook hypocalcemia as a treatable cause - it can arise at any age and cause seizures even in patients with previously normal calcium levels 4
• Do not diagnose alcohol withdrawal seizures without excluding other causes, especially in first-time seizure presentations 2, 3
• Do not start chronic antiseizure therapy for provoked seizures - treat the underlying cause instead 1, 2
• Do not assume cognitive decline is solely from seizures or medications - it may be a primary feature requiring separate management 7, 9, 6
• Monitor carefully for medication-induced psychiatric worsening in patients with pre-existing anxiety and depression, particularly in the first month of treatment 5

Ongoing Management

• If antiseizure therapy is started, use monotherapy at the minimum effective dose 1
• Consider discontinuation after 2 seizure-free years, involving the patient and family in the decision 1
• Provide education on avoiding high-risk activities, seizure triggers (sleep deprivation, alcohol), and first aid 1, 2
• Address psychiatric comorbidities with appropriate treatment, as depression and anxiety significantly impact quality of life and cognitive function 6