Readers' choice October 2012

Seizure: October 2012

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Readers' choice

Each month our Seizure Reviewers read the summaries of the articles in the latest issue of Seizure. They then decide which one should be readers' choice.

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Self reported adverse effects of mono and polytherapy for epilepsy

Tom Andrew, Kristijonas Milinis, Gus Baker, Udo Wieshmann
The Walton Centre for Neurology and Neurosurgery, Liverpool, UK

Abstract

Purpose

Adverse effects of anti-epileptic drugs (AEDs) can significantly affect the life of people with epilepsy. We used a register to determine if polytherapy with AED has more adverse effects than monotherapy.

Methods

We established a register for people with epilepsy (PWEE). Participants were requested to complete the Liverpool Adverse Event Profile (LAEP) to quantify adverse effects. We also recorded type of epilepsy, seizure control and AED including drug doses. Five hundred and seventy six complete data sets were available, monotherapy (n = 186), polytherapy (n = 325) and control subjects not taking AED (n = 65).

Results

The mean LAEP scores in polytherapy (45.56, confidence interval (CI) = 44.36–46.76) were significantly higher than the mean LAEP scores in monotherapy (42.29, CI = 40.65–44.02) and the mean LAEP scores in controls (33.25, CI = 31.05–35.44). Tiredness, memory problems and difficulty concentrating were the most common symptoms in patients taking AED and were consistently higher in polytherapy than in monotherapy. Tiredness was reported as always or sometimes being a problem in (polytherapy/monotherapy/controls) 82.5%/75.6%/64.6%, memory problems in 76%/63.2%/29.2% and difficulty concentrating in 68%/63.9%/30.8%. The proportion of seizure-free patients was significantly lower in the polytherapy group (17%) than in the monotherapy group (55%). Depression rates between the monotherapy and polytherapy groups were similar. Drug dosages were higher in polytherapy, however this did not reach statistical significance.

Conclusion

Patients on polytherapy had significantly higher LAEP scores than patients on monotherapy. This should be carefully discussed with the patient before a second AED is added.

Why I chose this article

By Linda Mayhew – Seizure reviewer

I am mum to Sally, now 17, who was diagnosed with epilepsy five years ago. We have tried at least seven different AED's singly and in varying combinations. She is currently taking one drug, as the combinations tried did not seem to offer her any overall benefit (some made things far worse !). We have also trialled the ketogenic diet and she had a VNS device fitted last year.

What was the aim of the study?

The study aimed to find out whether the adverse effects (AEs) experienced by people with epilepsy were greater if they were using more than one AED (polytherapy) rather than a single AED (monotherapy).

How was the research carried out?

Data was taken from the UK Anti-Epileptic Drugs Register (UKAED). This is a self-evaluation tool for people with epilepsy to report side-effects. It was set up in 2008 by The Walton Centre in Liverpool and made available online or as a form to be filled in at their clinic. 

People evaluate themselves against 19 possible adverse effects such as tiredness, memory loss, poor concentration etc. on a 1-4 scale. They also record the AEDs and dosages they are taking, their degree of seizure control and any other medical problems they have. Five hundred and seventy six people responded in the period between July 2008 and August 2011. Of these 186 were using a single AED, 325 were using more than one and a control group of 65 was included.

What did the researchers find out?

The finding of the research was that people taking more than one AED had significantly greater adverse effects in areas of tiredness, memory problems and concentration than those on a monotherapy. The comparison of different AED’s and combinations showed no significant differences, but as there is high number of AED’s and numerous combinations the numbers for such analysis were small in many cases.

The recommendation was that doctors should be cautious before recommending an add-on therapy and patients should be made aware of the increased risk of AE’s when more than one drug is used.

However, I think that although the report does state that “higher rates of uncontrolled epilepsy in the polytherapy group may affect the results”, I don’t think enough consideration of this has been given. The rate of uncontrolled epilepsy and other medical problems was much higher in the polytherapy group. Seizure control for monotherapy was 54 per cent but for polytherapy was just 16 per cent. Our experience has been that the drug regime tends to get more complex as the symptoms do! Obviously, the side-effects reported can also be associated with seizure frequency and severity. Maybe an attempt could be made to “untangle” these from drug side effects, either in the questionnaire or the data analysis. I fear that the real conclusion of the study might simply be that the less controlled and more severe your epilepsy is, the worse you feel, as you might expect.

A real issue of concern for someone considering an add-on therapy is whether it is likely to offer the same or better seizure control with less drug side-effects. For this, I think more specific questioning and/or analysis of data is required. Hopefully, a focused analysis will be possible if the body of data within this database increases.

Why is this research important to people with epilepsy?

Obviously what anyone with epilepsy wants is the best possible control of seizures without unwelcome side effects. This database will help add to the body of information on possible side effects from different AEDs and combinations of AEDs to help inform choice.

Why I like this study

I like this study because it is using self-reported data on factors that are very commonly experienced, can profoundly affect ones quality of life, but which can be difficult to quantify. Often it seems such factors are overlooked in studies that focus on the success or otherwise of AEDs based purely on seizure rate. Also I like that it attempts to evaluate interactive effects of multiple AED use, which is increasingly important as polytherapy becomes more common. I am particularly interested in this research as our family experience has made us very aware of what a confusing minefield AED prescribing can be.

Interview with the author

Dr Udo Wieshmann MD,PhD,FRCP

How did you become interested in epilepsy?

I always had an interest in neurology. I was inspired by my teachers Dr Hartmut Meierkord and Professor Simon Shorvon to specialise in epilepsy.

What issues inspired you to carry out this research?

Doctors are using many new drugs in epilepsy with unknown long term effects. We wanted to take a proactive role in monitoring drugs for epilepsy to increase drug safety. We established a UK wide Antiepileptic Drug register at the Walton Centre in Liverpool for this purpose.

Did you involve people with epilepsy when you were designing the study?

People with epilepsy who are attending my clinic at the Walton Centre have given me invaluable feed back.

What methods did you use and why?

We decided to use a self referral register because this enables us to obtain information from people with epilepsy directly.

What did you find out?

People who take more than one drug for epilepsy have significantly more side-effects than people who take just one drug. Our results also showed that tiredness, difficulties concentrating and memory problems were unfortunately extremely common.

What impact do you think your findings will have on the diagnosis/treatment/care?

I hope that our results will encourage doctors to review their patients medication to try to minimize side-effects.

What further research is needed in this area?

We need to find out which new drug has the least side effects and what types of side effects to expect. For example our UKAED register showed that 49 per cent of patients with epilepsy on Levetiracetam (Keppra®) reported anger as sometimes or always being a problem. Other researchers found similar results.

What other research are you involved with at the moment?

My college Prof. Tony Marson is launching SANAD II, a study comparing valproate and lamotrigine with levetriacetam. I hope we will gather important information. I am also involved in a study on neuroimaging of patients with epilepsy caused by certain brain tumours (oligodendrogliomas). We will of course continue to collect data for the UK Antiepileptic Drug register.