<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_joepi-2019-003_s_001"><h3>Background.</h3><p>The concept of rational polytherapy implies using a combination of antiepileptic drugs with synergistic effect, which in turn, may result in additive or reduced toxicity. This concept is not consensually accepted.</p></sec><sec id="j_joepi-2019-003_s_002"><h3>Aim.</h3><p>To present evidence in favour and against rational polytherapy.</p></sec><sec id="j_joepi-2019-003_s_003"><h3>Methods.</h3><p>Narrative literature review on PubMed and Medline databases using the following terms: epilepsy treatment, rational therapy/polytherapy, supraadditive treatment, drug-resistant epilepsy treatment. Cited references within selected articles were also evaluated.</p></sec><sec id="j_joepi-2019-003_s_004"><h3>Results.</h3><p>Against rational therapy is the evidence of clinical efficacy of the use of antiepileptic drugs with the same mechanism of action and without increased side-effects. Rational therapy may fail because while the addition of one antiepileptic drug to others with the same or different mechanisms of action leads to additive therapeutic efficacy, it also leads to more side effects. The evidence for the robust, unique, true synergism found between valproate and lamotrigine is questionable because the two drugs together may lead to complex pharmacokinetic interactions jeopardizing a consistent interpretation of the data. Data from studies with antiepileptic drugs with multiple mechanisms of action may be questionable because the same mechanism of action might not be responsible for drug efficacy or toxicity in different patients. Favouring rational therapy is the evidence that genetic animal models of seizures and drug-related neurotoxicity are ideal to evaluate the efficacy and toxicity of drug combinations, and that the most successful experimental combination of two antiepileptic drugs would be the one with a single mechanism of action and the other with a multiple mechanism of action.</p></sec><sec id="j_joepi-2019-003_s_005"><h3>Conclusion.</h3><p>Rational therapy is a sub-optimal, but worth being attempted strategy for the use of antiepileptic drugs in combination.</p></sec></abstract>

Background.The concept of rational polytherapy implies using a combination of antiepileptic drugs with synergistic effect, which in turn, may result in additive or reduced toxicity. This concept is not consensually accepted.Aim.To present evidence in favour and against rational polytherapy.Methods.Narrative literature review on PubMed and Medline databases using the following terms: epilepsy treatment, rational therapy/polytherapy, supraadditive treatment, drug-resistant epilepsy treatment. Cited references within selected articles were also evaluated.Results.Against rational therapy is the evidence of clinical efficacy of the use of antiepileptic drugs with the same mechanism of action and without increased side-effects. Rational therapy may fail because while the addition of one antiepileptic drug to others with the same or different mechanisms of action leads to additive therapeutic efficacy, it also leads to more side effects. The evidence for the robust, unique, true synergism found between valproate and lamotrigine is questionable because the two drugs together may lead to complex pharmacokinetic interactions jeopardizing a consistent interpretation of the data. Data from studies with antiepileptic drugs with multiple mechanisms of action may be questionable because the same mechanism of action might not be responsible for drug efficacy or toxicity in different patients. Favouring rational therapy is the evidence that genetic animal models of seizures and drug-related neurotoxicity are ideal to evaluate the efficacy and toxicity of drug combinations, and that the most successful experimental combination of two antiepileptic drugs would be the one with a single mechanism of action and the other with a multiple mechanism of action.Conclusion.Rational therapy is a sub-optimal, but worth being attempted strategy for the use of antiepileptic drugs in combination.

Rational polytherapy: Myth or reality?

Journal of Epileptology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

{"article-title":"Rational polytherapy: Myth or reality?"}

Background.The concept of rational polytherapy implies using a combination of antiepileptic drugs with synergistic effect, which in turn, may result in...

References	Synergistic combinations of AEDs
Rowan et al., 1983	VPA with ESM
Leach, Brodie, 1994	VGB with TGB
Brodie, Yuen, 1997	VPA with LTG
Stephen et al., 1998	LTG with TPM
Pisani et al., 1999	VPA with LTG
Brodie, Munford, 1999	CBZ with VGB or VPA
Perucca, 2006	STP with CLB
Moeller et al., 2009	VPA with LTG
Chung et al., 2010	LCM with LEV
Flores et al., 2012	LCM with AED sodium channel blockers
Brodie et al., 2014	RTG with AED sodium channel blockers or AEDs with other MOAs

References	Synergistic combinations of AEDs
Masuda et al., 1981	PB with PHT
Chez et al., 1994	VPA with PHT
Shank et al., 1994	TPM with CBZ and PB
Borowicz et al., 2002	GBP with CBZ, VPA, PHT and PB
Luszczki et al., 2003	LTG with TPM
Cuadrado et al., 2002	VPA with LTG
Luszczki et al., 2005*	TPM with FBM and OXC
Shandra et al., 2013	LCM with CBZ, LTG, TPM, GBP and LEV
Russmann et al., 2016	PER with ZNS

Rational polytherapy: Myth or reality?

Article Category: review-article

Data publikacji: 02 cze 2019

Zakres stron: 27 - 34

Otrzymano: 08 maj 2019

Przyjęty: 19 cze 2019

DOI: https://doi.org/10.21307/joepi-2019-003

Słowa kluczowe
antiepileptic drugs, clinical efficacy, epilepsy, mechanisms of action, tolerability, therapy

© 2019 José Pimentel., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Clinical synergistic antiepileptic drug (AED) combinations

Preclinical synergistic antiepileptic drug (AED) combinations

Rational polytherapy: Myth or reality?

Article Category: review-article

Data publikacji: 02 cze 2019

Zakres stron: 27 - 34

Otrzymano: 08 maj 2019

Przyjęty: 19 cze 2019

DOI: https://doi.org/10.21307/joepi-2019-003

Słowa kluczoweantiepileptic drugs, clinical efficacy, epilepsy, mechanisms of action, tolerability, therapy

© 2019 José Pimentel., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Clinical synergistic antiepileptic drug (AED) combinations

Preclinical synergistic antiepileptic drug (AED) combinations

Słowa kluczowe
antiepileptic drugs, clinical efficacy, epilepsy, mechanisms of action, tolerability, therapy