Topiramate is effective in the treatment of focal seizures in adults and children and in primary generalized tonic-clonic seizures. The drug is approved for the Lennox-Gastaut syndrome and may be effective in juvenile myoclonic epilepsy, infantile spasms, Dravet’s syndrome (severe myoclonic epilepsy in infancy), and even childhood absence seizures. The initial dose in newly diagnosed patients is typically 100 mg/d, but maintenance doses usually range from 200 to 400 mg/d. Most clinicians begin at a low dose (25–50 mg/d) and increase slowly to prevent adverse effects. Cognitive side effects commonly occur with topiramate and are a frequent reason for discontinuation. Affected patients experience impaired expressive language function (dysnomia and diminished verbal fluency), impaired verbal memory, and a general slowing of cognitive processing. These effects are unlike other antiseizure drugs and often occur without sedation or mood change. The incidence of cognitive side effects increases in a dose-dependent fashion, reaching 26% at a dose of 400 mg/d; however, some patients are completely unaffected even at higher dosages. Another troublesome adverse effect that commonly occurs with topiramate is paresthesias, typically occurring during initiation of therapy or at high doses; the symptoms may resolve with continuing treatment. Other dose-related adverse effects that occur frequently in the first 4 weeks of topiramate therapy are somnolence, fatigue, dizziness, nervousness, and confusion. Acute myopia and angle-closure glaucoma may require prompt drug withdrawal. Urolithiasis occurs in 0.5–1.5% of patients on long-term therapy and is more common in men. In some patients, carbonic anhydrase inhibition is associated with reduced serum bicarbonate that is usually asymptomatic but may result in nonspecific symptoms such as fatigue, anorexia, or nausea and vomiting. The potential for chronic untreated hyperchloremic non-anion gap metabolic acidosis for bone health is unknown. Decreased sweating (oligohydrosis) and an elevation in body temperature may occur during exposure to hot weather, mostly in children. Long-term topiramate therapy is often associated with significant weight loss, primarily due to a reduction in body fat mass. In clinical trials, 85% of adults receiving topiramate lost weight, which on average amounted to 5% of mean baseline body weight. Greater weight loss occurs in those with higher pretreatment weight. Weight loss is gradual and typically peaks at 12–18 months after initiation of therapy. Beneficial changes in lipid profile, glycemic control, and blood pressure may accompany the weight loss. Data in humans suggest a link between topiramate use in the first trimester of pregnancy and oral cleft formation in newborns (relative risk 16to 21-fold).