Drug treatment strategies for epilepsy revisited: starting early or late? One drug or several drugs?

Abstract

There are two popular strategies for current drug treatment of epilepsy; starting early may be better and polytherapy conveys advantages over monotherapy. This review briefly examines if the historical record is much of a guide to determine the clinical value of these two strategies. Great clinical scientists of the 19th and early 20th century, such as Sir William Gowers, and William Aldren Turner, offered vivid single case studies and showed early results of seizure remission in groups of subjects. The historical record offered, however, no evidence of clear clinical benefits for early treatment and polytherapy. Combination treatment was thought to be useful in only some cases. In agreement, current evidence shows no clear clinical benefit of starting treatment early, except perhaps in severe epilepsy. Polytherapy is clinically useful in a subgroup of subjects, but despite being a standard treatment strategy for over one hundred years, it has been poorly studied. In fact, there is no compelling experimental or clinical evidence for a difference in seizure outcome between monotherapy and polytherapy. This surprising finding should prompt a re‐appraisal regarding the need to test both strategies separately for the licensing of new antiepileptic drugs.

Patient reported adverse events among epileptic patients taking antiepileptic drugs

“…The broad spectrum activity of Phenobarbital against many types of seizure and its lower cost makes it to be used more frequently in our setting. 34 …”

Response to treatment schedules after the first antiepileptic drug failed

“…In previous studies, physicians suggested that the second AED should be considered when the first AED failed for lack of efficacy . However, the results of studies comparing combination therapy and alternative therapy have not provided evidence for which therapy should be chosen . Our study provided direct evidence that combination therapy offered larger probability of seizure freedom for patients with first AED failure due to lack of efficacy.…”

“…When the first drug fails, there are three options to control seizures: alternative therapy, combination therapy, or increase dosage of the first AED . Previous studies included patients with failure of the first AED due to insufficient efficacy or side effects, but the results have not demonstrated which therapy is better . Patients switching to a different AED because of side effects have a higher probability of seizure freedom on alternative therapy, which may bias the results …”

Antiepileptic Drugs, Polypharmacy, and Quality of Life in People Living with Epilepsy Managed in General Practice

“…14,17,19 QoL was not significantly related to the number of different ATC categories a participant had been prescribed medications from. Given that there is limited evidence for the effectiveness in seizure control whether AED monotherapy or polytherapy is used 13 and that AED polytherapy may be associated with a lower QoL, there seems little compelling need to use AED polytherapy in the management of epilepsy.…”

“…12 However, no compelling evidence exists for differences in seizure outcome whether monotherapy or polytherapy was used. 13 A recent study has shown that people with epilepsy who received AED monotherapy compared with polypharmacy experienced fewer ongoing seizures and reported a better quality of life (QoL) (when adjusting for seizure status). 14 This was supported by a recent US study that showed AED polypharmacy was associated with a worse QoL, even when adjusting for severity of epilepsy.…”