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Treatment of epilepsy for people with Alzheimer’s disease

Abstract

Background

Any type of seizure can be observed in Alzheimer’s disease (AD). Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with AD. There are pharmacological and non-pharmacological treatments for epilepsy in people with AD. There are no current systematic reviews to evaluate the efficacy and tolerability of the treatment. This review aims to review those different modalities.

Objectives

To assess the efficacy and tolerability of the treatment of epilepsy for people with Alzheimer’s disease (AD) (including sporadic AD and dominantly inherited AD).

Search methods

We searched the Cochrane Epilepsy Group Specialized Register (1 February 2016), the Cochrane Central Register of Controlled Trials (1 February 2016), MEDLINE (Ovid, 1 February 2016) and ClinicalTrials.gov (1 February 2016). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials’ registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.

Selection criteria

We included randomised and quasi-randomised controlled trials investigating treatment for epilepsy in people with AD, with the outcomes of proportion of seizure freedom or experiencing adverse events.

Data collection and analysis

Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.

Main results

We included one randomised controlled trial with 95 participants. Concerning the proportion of participants with seizure freedom, no significant differences were found in levetiracetam (LEV) versus lamotrigine (LTG) (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), in levetiracetam versus phenobarbital (PB) (RR 1.01, 95% CI 0.47 to 2.19), or in LTG versus PB (RR 0.84, 95% CI 0.35 to 2.02). It seemed that LEV could improve cognition and LTG could relieve depression; while PB and LTG could worsen cognition, and LEV and PB could worsen mood. We judged the quality of the evidence to be very low.

Authors’ conclusions

This review does not provide sufficient evidence to support LEV, PB and LTG for the treatment of epilepsy in people with AD. Regarding the efficacy and tolerability, no significant differences were found between LEV, PB and LTG. In the future, large randomised, double-blind, controlled, parallel-group clinical trials are required to determine the efficacy and tolerability of treatment for epilepsy in people with AD.

Plain language summary

Treatment of epilepsy for people with Alzheimer’s disease

Background
Alzheimer’s disease (AD) is a risk factor for increased seizures in the elderly. Seizures of any type can be observed in AD and are probably underestimated.

Study characteristics
We searched scientific databases for clinical trials comparing the active comparator with placebo (a ‘pretend’ treatment) or another active comparator for epilepsy in people with Alzheimer’s disease. We wanted to evaluate how well the treatment worked and if it had any side effects.

Key results
We included and analysed a randomised controlled trial (a clinical study where people are randomly put into one or two or more treatment groups) with 95 participants (identified from a literature search carried out on 1 February 2016). Concerning the proportion of participants with seizure freedom, no significant differences were found for levetiracetam versus lamotrigine (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), for levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19), or for lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression; while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood.

Quality of the evidence
The quality of the evidence from the study was very low and results should be interpreted with caution. Large randomised, double-blind, controlled, parallel-group clinical trials are required to determine how effective and well tolerated are treatments for epilepsy in people with AD.

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