Polytherapy in epilepsy: the experimental evidence.
Monotherapy is recommended preferentially among newly diagnosed epileptic patients. In monotherapy-resistant patients polytherapy may be necessary. Two antiepileptic drugs may produce antagonistic, additive, and supra-additive (synergistic) anticonvulsant effects. The drug combination providing the supra-additive effect seems of clinical significance. However, when the supra-additive anticonvulsant efficacy is also associated by a distinct increase in toxicity, the protective index may be not affected or even lowered. Synergistic interactions have been shown for the combinations of valproate-phenytoin/ethosuximide, topiramate-carbamazepine/phenobarbital and felbamate-all major conventional antiepileptics. In contrast, the protective action of conventional antiepileptics has not been affected by felbamate at subprotective doses against maximal electroshock in mice. This is indicative that synergism is evident at only some drug ratios. Potential antiepileptic drugs, excitatory amino acid antagonists and calcium channel inhibitors, generally enhanced the protection offered by antiepileptic drugs. The experimental data may be helpful for predicting which drug combinations may prove effective in epileptic patients.
Czuczwar
Stanisław J
SJ
Department of Pathophysiology, Lublin Medical University School, Jaczewskiego 8, 20-090, Lublin, Poland. czuczwar@galen.imw.lublin.pl
Borowicz
Kinga K
KK
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D000077236:Topiramate; D014227:Triazines / Q000627:therapeutic use
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077213:Lamotrigine