The role of polytherapy in the management of epilepsy: suggestions for rational antiepileptic drug selection

ABSTRACT

Introduction: Antiepileptic polytherapy may be indicated in patients experiencing drug-resistant epilepsy. To date, there are no evidence-based criteria on how to combine different antiepileptic drugs (AEDs) together, in order to obtain the best therapeutic response.

Areas covered: This paper reviews the available data about the various associations of AEDs in patients undergoing polytherapy, focusing on the most effective and well-tolerated polytherapies. Moreover, some controversial aspects of this topic are addressed.

Expert opinion: Nowadays, there are no guidelines on polytherapy in patients with epilepsy; thus, the management of pharmacoresistant epilepsy is still uncertain, except for valproate/lamotrigine combination, which seems to be the only one recommended. Data regarding mechanism of action, pharmacokinetics, tolerability, and, more importantly, the analysis of the valuable clinical studies of drug combinations can help physicians to choose the best and most effective AED association for each patient.

KEYWORDS:

• Antiepileptic polytherapy
• drug-resistant epilepsy
• antiepileptic drugs combinations
• synergism
• pharmacokinetics
• tolerability

Article highlights

• About 30% of epileptic patients have a drug-resistant epilepsy.

• Although monotherapy remains the therapy of choice for epilepsy, polytherapy is often required in resistant drug epilepsy.

• There are no specific criteria for the choice of anti-epileptic drugs to be combined together and different factors should be considered (patients’ characteristics, patients’ comorbidities, pharmacokinetics, safety, tolerability).

• Currently, the combination strategy consists in associating drugs with different mechanisms of action, to obtain a significantly better efficacy and minimum adverse effects.

• Human studies on combinations of antiepileptic drugs are insufficient and difficult to achieve.

In the next future, antiepileptic therapies will be based on precision medicine and not empirical evidence.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.