Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to Carbamazepine

• Published in: Epilepsia (Copenhagen) Vol. 46; no. 5; pp. 648 - 653
• Main Authors: Majkowski, Jerzy, Neto, Walter, Wapenaar, Robert, Van Oene, Joop
• Format: Journal Article
• Language: English
• Published: 350 Main Street , Malden , MA 02148 , USA and 9600 Garsington Road , Oxford , OX4 2XG , England Blackwell Science Inc 01.05.2005; Blackwell
• Subjects: Adolescent; Adult; Aged; Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiepileptic drug; Anxiety - chemically induced; Anxiety - epidemiology; Biological and medical sciences; Carbamazepine; Carbamazepine - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; Epilepsies, Partial - drug therapy; Feeding and Eating Disorders - chemically induced; Feeding and Eating Disorders - epidemiology; Female; Fructose - adverse effects; Fructose - analogs & derivatives; Fructose - therapeutic use; Headache - chemically induced; Headache - epidemiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Incidence; Male; Medical sciences; Meta-Analysis as Topic; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Paresthesia - chemically induced; Paresthesia - epidemiology; Pharmacology. Drug treatments; Placebos; Polytherapy; Randomized Controlled Trials as Topic - statistics & numerical data; Side effects; Sleep Wake Disorders - chemically induced; Sleep Wake Disorders - epidemiology; Time course; Time Factors; Topiramate; Weight Loss - drug effects; Human; Topiramate; Antiepileptic drug-Topiramate- Carbamazepine-Side effects-Time course-Polytherapy; Nervous system diseases; Epilepsy; Anticonvulsant; Tricyclic compound; Carbamazepine; Cerebral disorder; Mood stabilizer; Central nervous system disease; Complication; Localization
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2005.35904.x

Purpose: To explore the time course of treatment‐emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double‐blind, placebo‐controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment‐resistant partial‐onset seizures. The daily incidence and mean duration of the most common (≥5% incidence) AEs were calculated for patients completing the 12‐week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.