What are the prescription guidelines for focal seizures in Indian clinical practice for IPD (In-Patient Department), OPD (Out-Patient Department), emergency, and ICU (Intensive Care Unit) settings?

Prescription Guidelines for Focal Seizures in Indian Clinical Practice

For focal seizures in Indian settings, carbamazepine or lamotrigine should be the first-line monotherapy across all settings (OPD, IPD, Emergency, ICU), with phenobarbital as an alternative when cost is a limiting factor. 1, 2, 3

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OPD (Outpatient Department) Prescription

First-Line Monotherapy Options

Carbamazepine is the preferred first-line agent for focal seizures in resource-limited settings:

• Adults and children >12 years: Start 200 mg twice daily (400 mg/day), increase weekly by 200 mg/day using 3-4 divided doses until optimal response; maintenance 800-1200 mg/day; maximum 1200 mg/day (up to 1600 mg/day in rare adult cases) 4, 2
• Children 6-12 years: Start 100 mg twice daily (200 mg/day), increase weekly by 100 mg/day; maintenance 400-800 mg/day; maximum 1000 mg/day 4
• Children <6 years: Start 10-20 mg/kg/day in 2-3 divided doses, increase weekly; maximum 35 mg/kg/day 4

Lamotrigine is superior to carbamazepine for treatment failure outcomes and should be considered when tolerability is a concern:

• High-certainty evidence shows lamotrigine has better treatment retention than carbamazepine (HR 1.26,95% CI 1.10-1.44 favoring lamotrigine) 2
• Lamotrigine performs better than most other treatments for treatment failure due to adverse events 2

Phenobarbital should be offered as first-line when cost is the primary constraint:

• Given acquisition costs, phenobarbital is recommended if availability can be assured in low- and middle-income countries 1
• However, phenobarbital has higher treatment failure rates compared to lamotrigine (HR 1.97,95% CI 1.45-2.67) 2

Alternative First-Line Options

Levetiracetam can be considered if no psychiatric history exists:

• Shows similar efficacy to lamotrigine for treatment failure (HR 1.01,95% CI 0.88-1.20) 2
• Better tolerability profile than older agents 3, 5
• Avoid in patients with history of mood, anxiety, or behavioral disorders 3

Oxcarbazepine is an appropriate alternative:

• First-line option with better tolerability than carbamazepine 3, 5
• Slightly higher treatment failure rate than lamotrigine (HR 1.30,95% CI 1.02-1.66) 2

Medications to Avoid as First-Line

Phenytoin, topiramate, and gabapentin have significantly higher treatment failure rates:

• Phenytoin vs lamotrigine: HR 1.44 (95% CI 1.11-1.85) 2
• Topiramate vs lamotrigine: HR 1.50 (95% CI 1.23-1.81) 2
• Gabapentin vs lamotrigine: HR 1.53 (95% CI 1.26-1.85) 2

OPD Prescription Format

Rx
1. Tab Carbamazepine 200 mg - 1 tablet twice daily with meals
   Increase by 200 mg weekly as tolerated
   Target: 800-1200 mg/day in divided doses
   
OR

Tab Lamotrigine 25 mg - [dose per titration schedule]
(Preferred if tolerability/adherence concerns)

2. Folic acid 5 mg once daily (if childbearing potential)

3. Advise: Take with meals, avoid high-risk activities until seizure-free
4. Follow-up: 2 weeks for dose titration, then monthly
5. Monitor: Seizure frequency, adverse effects, drug levels if available

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Emergency Department Prescription

Acute Seizure/Status Epilepticus Management

First-Line: IV Benzodiazepines

• Lorazepam 4 mg IV slowly (2 mg/min) is preferred over diazepam 1, 6, 7
• If seizures continue after 10-15 minutes, repeat lorazepam 4 mg IV 7
• If IV access unavailable: Rectal diazepam or IM phenobarbital 1
• IM diazepam is NOT recommended due to erratic absorption 1

Second-Line Agents (if seizures persist after benzodiazepines):

All three agents have equal efficacy (ESETT trial - Class I evidence):

• Levetiracetam: 47% seizure cessation 6
• Fosphenytoin: 45% seizure cessation 6
• Valproate: 46% seizure cessation 6

Levetiracetam 30-50 mg/kg IV (maximum 3000 mg) at 100 mg/min:

• Lowest hypotension risk (0.7%) 6, 8
• Intubation rate 20% 6
• Favorable side effect profile, fewer drug interactions 6
• May cause nausea and rash 6

Valproate 20-30 mg/kg IV (maximum 3000 mg) at maximum 10 mg/kg/min:

• Hypotension risk 1.6% 6, 8
• Intubation rate 16.8% 6
• Rapid administration possible, minimal cardiorespiratory effects 6
• Contraindicated in liver disease, risk of thrombocytopenia 6
• 88% efficacy in refractory status epilepticus 1

Phenytoin 18-20 mg/kg IV (or fosphenytoin 18-20 PE/kg) at maximum 50 mg/min:

• Hypotension risk 3.2% 6
• Intubation rate 26.4% 6
• Risk of cardiac dysrhythmias 6, 9
• Must dilute before IV use, inject slowly with repeated aspiration 9
• Contraindicated in sinus bradycardia, AV block, Adams-Stokes syndrome 9

Critical Simultaneous Management

While administering antiseizure medications, immediately evaluate and treat:

• Check blood glucose and treat hypoglycemia 6
• Assess for hyponatremia 6
• Ensure adequate oxygenation, assess for hypoxia 6
• Consider toxicology screen 6
• Evaluate for CNS or systemic infection 6
• Consider neuroimaging if concern for stroke, hemorrhage, or mass 6

Emergency Prescription Format

Rx (Status Epilepticus Protocol)
1. Inj Lorazepam 4 mg IV slow push (2 mg/min)
   Repeat once after 10-15 min if seizures continue
   
2. If seizures persist, give ONE of:
   a) Inj Levetiracetam 1500-3000 mg (30-50 mg/kg) IV over 15 min
   OR
   b) Inj Sodium Valproate 1200-2000 mg (20-30 mg/kg) IV at 10 mg/kg/min
   OR
   c) Inj Phenytoin 1000-1500 mg (18-20 mg/kg) IV at 50 mg/min
   
3. Concurrent: IV access, O2, monitor vitals, check glucose
4. Investigations: RBS, electrolytes, CBC, LFT, drug levels
5. Airway equipment at bedside, prepare for intubation if needed

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IPD (Inpatient Department) Prescription

Post-Emergency Stabilization

After acute seizure control, initiate or continue maintenance therapy:

If patient was on no prior AED:

• Start carbamazepine or lamotrigine as per OPD dosing 2, 3
• Phenobarbital if cost-constrained 1

If breakthrough seizure on existing AED:

• Optimize current AED dose before adding second agent 2
• Check drug levels if available 4
• Assess adherence and drug interactions 3

If requiring second AED (after benzodiazepine + second-line agent in emergency):

• Continue the effective second-line agent (levetiracetam, valproate, or phenytoin) 6
• Transition to oral formulation when able 9
• Add or optimize baseline AED 2

IPD Prescription Format

Rx (Post-Acute Management)
1. Tab Carbamazepine 200 mg - 1 tablet TDS with meals
   (or continue IV/oral agent that controlled seizures)
   
2. Tab Levetiracetam 500 mg - 1 tablet BD
   (if used in emergency and effective)
   
3. Tab Folic acid 5 mg OD
4. Seizure precautions: Padded bed rails, supervised ambulation
5. Monitor: Seizure frequency, drug levels, CBC, LFT
6. Investigations: MRI brain, EEG when stable
7. Avoid: Abrupt discontinuation of AEDs

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ICU Prescription

Refractory Status Epilepticus

If seizures continue despite first-line benzodiazepines and second-line agents:

Valproate 30 mg/kg IV at 6 mg/kg/hour for refractory convulsive status epilepticus:

• 88% efficacy in controlling seizures within 1 hour after failure of diazepam and phenobarbital 1

Levetiracetam 30 mg/kg IV for refractory status epilepticus:

• Equal efficacy to valproate (73% vs 68%) 1
• 67% efficacy when used after benzodiazepines 1

Phenobarbital IM may be considered when IV access is problematic:

• Used in refractory cases 1

Continuous Monitoring Requirements

Essential ICU monitoring:

• Continuous EEG monitoring to detect non-convulsive status epilepticus 6
• Continuous ECG, blood pressure, respiratory function monitoring 9
• Airway patency must be assured, ventilatory support ready 9, 7
• Monitor for prolonged sedation effects, especially with multiple doses 7

ICU Prescription Format

Rx (Refractory Status Epilepticus)
1. Inj Sodium Valproate 2000 mg (30 mg/kg) IV loading
   Then 400 mg/hour (6 mg/kg/hour) continuous infusion
   
   OR
   
   Inj Levetiracetam 2000 mg (30 mg/kg) IV over 15 min
   
2. Continue Inj Lorazepam 2-4 mg IV PRN for breakthrough seizures
3. Mechanical ventilation as needed
4. Continuous monitoring: EEG, ECG, BP, SpO2
5. Investigations: Serial drug levels, CBC, LFT, electrolytes
6. Seizure precautions: Padded rails, 1:1 nursing
7. Treat underlying cause: Infection, metabolic derangement
8. Avoid: Abrupt withdrawal of sedation

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Common Pitfalls to Avoid

Medication-Related Pitfalls:

• Never give IM diazepam - erratic absorption makes it ineffective 1
• Never inject phenytoin rapidly - maximum 50 mg/min to avoid hypotension and cardiac dysrhythmias 6, 9
• Always dilute phenytoin before IV use - inject slowly with repeated aspiration to avoid intra-arterial injection 9
• Avoid valproate in liver disease - contraindicated due to hepatotoxicity risk 6
• Avoid phenytoin in cardiac conduction disorders - contraindicated in bradycardia, AV block 9

Clinical Management Pitfalls:

• Not recognizing non-convulsive status epilepticus - requires EEG monitoring in ICU 6
• Overlooking underlying causes - always search for and treat hypoglycemia, hyponatremia, hypoxia, infection, structural lesions 6
• Inadequate airway management - ventilatory support must be readily available, especially with benzodiazepines 7
• Premature ambulation - patients may have prolonged sedation for 24-48 hours, especially elderly 7

Treatment Strategy Pitfalls:

• Starting AED after single unprovoked seizure - not routinely recommended 1
• Abrupt AED discontinuation - may precipitate status epilepticus; taper gradually 9
• Polytherapy before optimizing monotherapy - maximize single agent before adding second 1, 2
• Not checking drug levels - monitoring increases efficacy and safety 4

Special Population Considerations:

• Women of childbearing potential: Avoid valproate if possible, give folic acid 5 mg daily with all AEDs 1
• Elderly patients (>50 years): May have more profound and prolonged sedation with benzodiazepines 7
• Patients with psychiatric history: Avoid levetiracetam due to behavioral adverse effects 3