Rational polytherapy.
Monotherapy has been considered the gold standard for drug treatment of epilepsy. However, there is renewed interest in polytherapy because of the advent of new drugs with fewer drug interactions and novel mechanisms of action, and the realization that most patients with refractory epilepsy are eventually treated with drug combinations. Careful consideration must be given to drug additions and conversions; it may be less risky to add a drug than to convert from one monotherapy to another in patients with frequent or severe seizures. Rational choice of drug combinations is, at present, based more on avoidance of pharmacodynamic or pharmacokinetic side effects than on evidence for supra-additive efficacy. There are indications that combinations of two sodium-channel blocking agents are less effective than combinations of drugs with different primary mechanisms of action, and some human studies suggest that lamotrigine and valproate may be synergistic for efficacy. However, more animal and human research is needed, with attention to the effects of various combinations on both toxicity and seizure control.
French
Jacqueline A
JA
New York University School of Medicine, New York, New York, USA. Jacqueline.french@nyumc.org
Faught
Edward
E
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D000077213:Lamotrigine; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine