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Updated: May 5, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Carbamazepine and phenytoin: combination versus single drug therapy
N Y Lorenzo1, E B Bromfield, W H Theodore
1Department of Neurology, Mayo Clinic and Foundation, Guggenheim 1521, 200 1st Street S.W., Rochester, MN55905Department of Neurology, New England Medical Center and Tufts University School of Medicine, Boston, MAClinical Epilepsy Section, Medical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Abstract:
The records of 18 patients with intractable partial seizures who were observed on an in-patient epilepsy unit during single drug treatment with carbamezepine (CBZ) or phenytoin (PHT) and during combination therapy with both drugs were evaluated retrospectively. Seizure frequency was significantly lower during combination therapy (p < 0.01) and toxicity, as measured by an eight point objective scale, did not increase significantly (p > 0.10). In addition subjective signs of clinical toiicity (e.g. nausea, ataxia, etc.) increased only slightly during combination versus monotherapy. These findings were consistently seen whether the data were evaluated in total (i.e. treatment periods at least 7 weeks) or evaluated by using standardized 35 day treatment periods. In the absence of a blinded clinical trial evaluating PHT/CBZ combination, these findings support consideration of this combination in Intractable patients who have failed rigorously administered mono-therapy trials, recognizing however that only a small percentage of patients will improve on combination therapy.
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