Weight Gain Associated with Valproate vs. Lamotrigine Monotherapy in Patients with Epilepsy: A Randomized, Double-Blind Clinical Trial
Abstract number :
2.004
Submission category :
Year :
2000
Submission ID :
2932
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Victor Biton, Waqar Mirza, Georgia D Montouris, Alain Vuong, Anne E Hammer, Pamela S Barrett, Arkansas Epilepsy Ctr, Little Rock, AR; Neurology and Epileptology, Bridgeton, MO; Comprehensive Epilepsy Care Ctr, Chesterfield, MO; Glaxo Wellcome Inc, RTP, NC
RATIONALE: LAMICTAL? (LTG) and DEPAKOTE? (VPA) are commonly used antiepileptic drugs (AEDs). Marked weight gain is frequently reported with VPA. Controlled trials of adjunctive therapy with LTG suggest it does not cause weight gain, but this outcome has not been assessed using LTG as monotherapy. METHODS: Patients were ?12 years old with new onset partial or generalized seizures. Patients who had used LTG or VPA for >90 days prior to screen were excluded. Patients were randomized 1:1 to LTG or VPA, entered an 8-week Escalation, then a 24-week Maintenance Phase. The target doses were 200-500 mg/day for LTG and 20-60 mg/kg/day for VPA based on clinical response. The primary endpoint was weight change. RESULTS: LTG group: 65 patients, 58% female, mean age 34.5 yrs. VPA group: 68 patients, 54% female, mean age 30.1 yrs. The screen weight was 155 lb ? 41 for LTG patients, 161 lb ? 45 for VPA patients. During Maintenance, the mean dose was 254 mg/day for LTG and 1822 mg/day for VPA. The mean weight changes at weeks 10, 14, 20, 26, 32 were higher (p?0.002 for all weeks) in VPA patients (5.8, 7.8, 8.6, 10.7, 12.8 lb) than in LTG patients (1.4, 1.6, 0.7, 0.8, 1.3 lb). When weight was compared to the patient's screen weight, ~4 times as many patients taking VPA gained ?5% (62% for VPA, 18% for LTG, p<0.001), or ?10% (38% for VPA, 8% for LTG, p<0.001). Mean weight change did not differ by age or gender. The percentage of patients remaining on treatment at the end of the study was 71% (LTG) and 56% (VPA, p=0.05). During this 32-week study the percentage of patients who were seizure-free was 29% (LTG) and 26% (VPA). For most common (>10%) drug-related adverse events, nausea, somnolence, tremor and vomiting were higher with VPA (24, 24, 28, 13%) than with LTG (12, 8, 3, 6%); asthenia and headache were higher with LTG (20, 14%) than VPA (16, 6%). CONCLUSIONS: In this monotherapy study, patients taking LTG had generally stable weight and those on VPA had a marked increase in weight. The weight gain with VPA was significant within 10 weeks of starting therapy and continued to increase during the study. LTG appeared to have comparable efficacy with better tolerability than VPA.