Treatment of epilepsy for people with Alzheimer's disease

Background
Alzheimer's disease is a risk factor for increased seizures in older people. Seizures of any type can be observed in Alzheimer's disease and are probably underestimated.

Study characteristics
We searched scientific databases for clinical trials comparing medication and non-medication-based treatments 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 analyzed one randomized controlled trial (a clinical study where people are randomly put into one or two or more treatment groups) with 95 participants. Concerning the proportion of participants with seizure freedom, no significant differences were found between the antiepileptic drugs (levetiracetam versus lamotrigine, levetiracetam versus phenobarbital, and lamotrigine versus phenobarbital). It seemed that levetiracetam could improve cognition (thinking) 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 randomized controlled trials, which have a double-blind parallel-group design, are required to determine how effective and well tolerated treatments are for epilepsy in people with Alzheimer's disease.

The evidence is current to July 2018.

Authors' conclusions: 

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

Read the full 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 these treatments; this review aims to review those different modalities. This is an updated version of the original Cochrane Review published in Issue 11, 2016.

Objectives: 

To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with AD (including sporadic AD and dominantly inherited AD).

Search strategy: 

For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). 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 randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with AD, with the outcomes of proportion of participants with seizure freedom or proportion of participants 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 randomized controlled trial on pharmacological interventions with 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam (LEV) versus lamotrigine (LTG) (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), LEV versus phenobarbital (PB) (RR 1.01, 95% CI 0.47 to 2.19), or 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. Unclear risk of bias was found in allocation, blinding and selective reporting. We judged the quality of the evidence to be very low.

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