Topiramate in refractory epilepsy: a prospective observational study.
OBJECTIVE
This prospective observational study explored the efficacy and tolerability of topiramate (TPM) in patients with refractory epilepsy attending a single outpatient clinic.


METHODS
One hundred seventy patients (82 men, 88 women, aged 18-75 years) with refractory localization-related (n = 134) or idiopathic generalized epilepsy (n = 36) were started on adjunctive TPM using a standard titration schedule. TPM was introduced after a 3-month prospective baseline, and doses were adjusted according to clinical response. End points were seizure freedom for 6 months, > or =50% seizure reduction for 6 months compared with baseline at the highest tolerated TPM dose (responder), or discontinuation of TPM because of side effects, lack of efficacy, or both.


RESULTS
Thirty-nine (23%) patients were seizure-free, and 80 (47%) more patients had a useful therapeutic response. Thirteen seizure-free patients and 16 responders took 100 mg of TPM daily or less. TPM was discontinued in 51 (30%) patients. The most common side effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Concomitant antiepileptic drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM monotherapy, eight of whom remained seizure-free. Final TPM doses and concentrations varied widely among the three outcome groups.


CONCLUSIONS
TPM was efficacious as add-on and monotherapy in patients with refractory partial and generalized seizures in everyday clinical use. A good response was obtained in many patients with TPM doses substantially lower than those studied in regulatory clinical trials. The wide variation in dose-response and dose-toxicity relationships may reflect different neurobiologies causing refractory epilepsy and differential efficacy of AED combinations.
Stephen
L J
LJ
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Sills
G J
GJ
Brodie
M J
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000627:therapeutic use; D011446:Prospective Studies; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D010672:Phenytoin; D000077213:Lamotrigine