What is Topiramate (anticonvulsant medication) used for?

Topiramate: Clinical Uses

Topiramate is FDA-approved for treating epilepsy and migraine prophylaxis, while the combination phentermine/topiramate ER is FDA-approved for chronic weight management in adults with obesity. 1

FDA-Approved Indications

Epilepsy Treatment

• Monotherapy for partial-onset seizures in patients 10 years and older 2
• Adjunctive therapy for partial-onset seizures in adults and children over age 2 2
• Primary generalized tonic-clonic seizures of nonfocal origin in children and adults 3, 4
• Lennox-Gastaut syndrome in pediatric patients 5

Migraine Prophylaxis

• FDA-approved for migraine prevention, with firmly established efficacy 6
• This indication makes phentermine/topiramate ER particularly useful in patients with both obesity and comorbid migraines 1, 7

Weight Management (Combination Therapy Only)

• Phentermine/topiramate ER is FDA-approved for chronic weight management in adults with BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related complication (hypertension, type 2 diabetes, dyslipidemia) 1
• Topiramate monotherapy is NOT FDA-approved for weight loss, though many prescribers use it off-label for this purpose 1

Mechanism of Action

Antiepileptic Effects

• Blocks voltage-gated sodium channels, preventing seizure spread 4
• Inhibits voltage-gated calcium channels 4
• Inhibits glutamate-mediated neurotransmission 4
• Enhances GABA-mediated neurotransmission through modulation of GABA receptors 4
• Inhibits carbonic anhydrase isoenzyme 4

Weight Loss Effects

• Reduces energy intake through modulation of GABA receptors in the CNS, though the exact mechanism remains unclear 1
• Decreases appetite and increases satiation in humans 1, 7
• In animal studies, topiramate increases energy expenditure by reducing bioenergetic efficiency, but this has not been demonstrated in humans 1

Off-Label Uses

Weight Management (Monotherapy)

• Many prescribers use topiramate monotherapy off-label for weight loss despite lack of FDA approval 1
• Prospective, randomized, placebo-controlled trials have demonstrated efficacy in patients with overweight and obesity, but most studies are less than 12 months in duration 1

Eating Disorders

• Topiramate has been used to manage some eating disorders, though most published effects are case series or case reports 1

Other Neuropsychiatric Conditions

• Substance dependence, bipolar disorder, and neuropathic pain have been investigated, though evidence is limited 6
• Possible neuroprotective agent in preclinical studies 4, 6

Clinical Efficacy Data

Epilepsy

• Target dose of 100 mg/day for initial monotherapy in adults with new-onset seizures 3
• Optimum dose for most patients does not exceed 400 mg/day, though adjunctive use with enzyme-inducing drugs and refractory seizures may require higher dosages 3
• Efficacy maintained for up to 7 years in long-term studies 8

Weight Loss (Phentermine/Topiramate ER)

• At 7.5 mg/46 mg dose: 7.8% body weight loss compared to 1.2% with placebo 1, 7
• At 15 mg/92 mg dose: 9.8% body weight loss compared to 1.2% with placebo at 1 year 1, 7
• At 108 weeks (SEQUEL trial): 10.5% body weight loss with 15 mg/92 mg dose compared to 1.8% with placebo 1

Important Safety Considerations

Teratogenicity

• Topiramate causes orofacial clefts when exposed during the first trimester 7, 9
• Pregnancy test required before initiation in women of childbearing potential 7, 9
• Reduces efficacy of hormonal contraceptives; barrier methods should be used 7, 9

Common Adverse Effects

• CNS effects are most common: somnolence, dizziness, fatigue, insomnia, cognitive dysfunction (especially problems with expressive speech and verbal memory) 3, 4
• Weight loss (which may be desirable in obesity treatment but problematic in epilepsy patients) 3, 4
• Paresthesias 3, 4
• Nephrolithiasis (kidney stones) 3, 5

Discontinuation

• Never stop topiramate abruptly due to seizure risk 9
• Taper gradually: for phentermine/topiramate ER, take one capsule every other day for at least 1 week before stopping 9

Monitoring Requirements (for Phentermine/Topiramate ER)

• Blood pressure and heart rate monitoring at each visit due to the phentermine component 7
• Monthly visits for first 3 months, then every 3 months thereafter 7

Contraindications for Phentermine/Topiramate ER

• Uncontrolled hypertension or active coronary disease 7
• History of nephrolithiasis 7
• Hyperthyroidism, glaucoma 7
• Anxiety, insomnia, history of drug abuse 7
• Recent MAOI use 7
• Women of childbearing potential without reliable contraception 7