Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study.
OBJECTIVE
Monotherapy has been the gold standard in epilepsy treatment for the last 20 years, partly because of the reputation for increased toxicity of polytherapy. However, monotherapy and polytherapy have not been compared in a double-blind clinical trial. Open trials that compared the two treatments were not optimally designed and compared the two at unequal drug loads (i.e., at nonequivalent dosages). We report on a double-blind clinical trial in which a combination of carbamazepine (CBZ) and valproate (VPA) was compared with CBZ monotherapy. Patients started with equal drug loads, and neurotoxicity was the primary outcome measure.


METHODS
The 130 adult patients with untreated generalized tonic-clonic and/or partial seizures were randomized to equal drug loads of either monotherapy (400 mg CBZ per day) or polytherapy (200 mg CBZ plus 300 mg VPA per day). Outcome was measured by seizure counts, clinimetric epilepsy scales, and neuropsychological tests at baseline, at 2 and 12 months, and irregularly between 2 and 12 months.


RESULTS
No statistical differences were found between the two treatments in the reduction of seizure frequencies, in overall neurotoxicity, or in overall systemic toxicity. The frequencies and clinimetric scores of certain adverse effects did differ (e.g., more monotherapy patients remained sedated, and more polytherapy patients gained weight). Fewer polytherapy patients withdrew because of adverse effects (14 vs. 22%), although this did not reach statistical significance (p=0.15). Neuropsychological assessment did not show significant differences.


CONCLUSIONS
No differences were found in overall neurotoxicity between monotherapy and polytherapy.
Deckers
C L
CL
Institute of Neurology, University Medical Center Nijmegen, Nijmegen, the Netherlands. clp.deckers@planet.nl
Hekster
Y A
YA
Keyser
A
A
van Lier
H J
HJ
Meinardi
H
H
Renier
W O
WO
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006304:Health Status; D006801:Humans; D019964:Mood Disorders / Q000139:chemically induced; D011788:Quality of Life; D012893:Sleep Wake Disorders / Q000139:chemically induced; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid