Topiramate Dosing for Epilepsy and Migraine
For epilepsy, start topiramate at 25-50 mg daily and titrate by 25-50 mg weekly to a target dose of 200-400 mg/day in divided doses for adjunctive therapy or 400 mg/day for monotherapy; for migraine prophylaxis, target 100 mg/day using the same gradual titration schedule. 1, 2
Epilepsy Dosing
Monotherapy
- Target dose: 400 mg/day in two divided doses 2
- Titration schedule over 6 weeks: 2
- Week 1: 25 mg twice daily (50 mg/day)
- Week 2: 50 mg twice daily (100 mg/day)
- Week 3: 75 mg twice daily (150 mg/day)
- Week 4: 100 mg twice daily (200 mg/day)
- Week 5: 150 mg twice daily (300 mg/day)
- Week 6: 200 mg twice daily (400 mg/day)
- Only 58% of patients achieve the full 400 mg/day dose; the mean achieved dose is 275 mg/day 2
Adjunctive Therapy (Add-on Treatment)
- Target dose: 200-400 mg/day in two divided doses for partial seizures 2
- Target dose: 400 mg/day in two divided doses for primary generalized tonic-clonic seizures 2
- Start at 25-50 mg/day and increase by 25-50 mg weekly 1, 2
- Doses above 400 mg/day (600-1,600 mg/day) have been studied but show no additional benefit for partial seizures 2
- Maximum studied dose is 1,600 mg/day 3
Pediatric Epilepsy (Ages 2-16)
- Target dose: 5-9 mg/kg/day in two divided doses 2
- Start at 25 mg nightly (or 1-3 mg/kg/day) for the first week 2
- Increase at 1-2 week intervals by 1-3 mg/kg/day increments 2
Migraine Prophylaxis Dosing
- Target dose: 100 mg/day 1, 4
- Use the same gradual titration: start at 25-50 mg daily and increase by 25-50 mg every 3-7 days as tolerated 1
- This slower titration (25 mg weekly increments) reduces adverse events that commonly occur during the titration phase 5
- Topiramate significantly reduces monthly migraine days by approximately 3.5 days compared to placebo in chronic migraine 6
- In chronic migraine specifically, the mean modal dose achieved was 100 mg/day 6, 7
Critical Safety Considerations
Discontinuation Protocol
- Never stop topiramate abruptly—always taper gradually to minimize seizure risk 1, 3, 8
- For standard formulations, taper over at least one week 8
- For combination phentermine/topiramate, take one capsule every other day for at least 1 week before stopping 3
Teratogenicity
- Topiramate increases the risk of orofacial clefts when exposed during the first trimester 1, 3, 8
- Pregnancy testing is required for women of childbearing potential before initiating therapy 3
- Topiramate reduces the efficacy of hormonal contraceptives—counsel all women of reproductive age 1, 3, 8
Common Adverse Effects
- Paresthesia is the most common side effect (28.8% vs 0% placebo in migraine trials) 7
- Other frequent effects include dizziness, dysgeusia, insomnia, constipation, dry mouth, fatigue, and anorexia 8, 4
- Migraineurs experience different and more frequent adverse effects than epilepsy patients at the same doses, with 2.5-3.0 times higher risk of paresthesia and 2.5 times higher dropout rates at 50 mg doses 9
- Cognitive complaints and taste alterations occur specifically in migraine patients, while behavioral ADRs occur specifically in epilepsy patients 9
Serious Adverse Effects
- Metabolic acidosis due to carbonic anhydrase inhibition 1
- Increased risk of kidney stones—ensure adequate hydration 1
- Acute angle-closure glaucoma 4
- Hepatotoxicity (uncommon) 4
Renal Impairment Adjustments
- Patients with creatinine clearance <70 mL/min require dose adjustments 2
- Those on hemodialysis may need supplemental doses 8
Drug Interactions
- Addition of topiramate to phenytoin may require phenytoin dose adjustment 2
- Addition or withdrawal of phenytoin or carbamazepine during topiramate therapy may require topiramate dose adjustment 2
- Plasma concentration monitoring is not necessary to optimize therapy 2