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A viewpoint on rational and irrational fixed-drug combinations.
Barbara Błaszczyk1, Barbara Miziak2, Piotr Czuczwar2,3
1a Faculty of Health Sciences , High School of Economics, Law and Medical Sciences , Kielce , Poland.
Expert Review of Clinical Pharmacology
|July 20, 2018
Summary
Drug combinations for epilepsy can be beneficial or detrimental. Lamotrigine and carbamazepine showed negative interactions, while lamotrigine and valproate showed promise for treating drug-resistant epilepsy.
Area of Science:
- Pharmacology
- Neurology
- Clinical Pharmacy
Background:
- Approximately 30% of epilepsy patients exhibit resistance to monotherapy, necessitating research into effective drug combinations.
- This review critically examines beneficial and irrational antiepileptic drug (AED) combinations from both experimental and clinical perspectives.
- Focus is placed on synergistic, additive, or antagonistic effects, including anticonvulsant and neurotoxic outcomes, alongside pharmacokinetic data.
Purpose of the Study:
- To evaluate the efficacy and safety of combined antiepileptic drug therapies.
- To identify optimal and suboptimal drug pairings for epilepsy management.
- To provide evidence-based recommendations for clinical practice regarding AED polypharmacy.
Main Methods:
- Systematic review of experimental studies assessing AED interactions (synergy, additivity, antagonism).
- Analysis of clinical data from studies involving significant patient cohorts, excluding case reports.
- Consideration of anticonvulsant effects, neurotoxicity, and pharmacokinetic profiles of drug combinations.
Main Results:
- Experimental data suggest negative interactions between lamotrigine and carbamazepine, lamotrigine and oxcarbazepine, and oxcarbazepine and phenytoin.
- Clinical reports offer mixed conclusions regarding the lamotrigine-carbamazepine combination.
- Positive experimental and clinical evidence supports combinations such as lamotrigine+valproate, carbamazepine+valproate, and levetiracetam+valproate.
Conclusions:
- While experimental data provide valuable insights, clinical evaluation is crucial due to limitations such as animal models and acute drug administration.
- Lamotrigine+valproate combination shows potential for clinical recommendation.
- Several AED combinations demonstrate promise for improving outcomes in drug-resistant epilepsy, warranting further clinical investigation.
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