Elsevier

Epilepsy Research

Volume 37, Issue 1, October 1999, Pages 81-87
Epilepsy Research

Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy

https://doi.org/10.1016/S0920-1211(99)00039-XGet rights and content

Abstract

In a multicentre, double-blind trial 150 elderly patients (mean age 77 years) with newly diagnosed epilepsy were randomised in a 2:1 ratio to treatment with lamotrigine (LTG) or carbamazepine (CBZ). Following a short titration period, the dosage was individualised for each patient while maintaining the blind over the next 24 weeks. The main difference between the groups was the rate of drop-out due to adverse events (LTG 18% versus CBZ 42%). This was in part a consequence of the lower rash rate with LTG (LTG 3%, CBZ 19%; 95% CI 7–25%). LTG-treated patients also complained less frequently of somnolence (LTG 12%, CBZ 29%; 95% CI 4–30%). Although there was no difference between the drugs in time to first seizure, a greater percentage of LTG-treated patients remained seizure-free during the last 16 weeks of treatment (LTG 39%, CBZ 21%; P=0.027). Overall, more patients continued on treatment with LTG than CBZ (LTG 71%, CBZ 42%; P<0.001) for the duration of the study. The hazard ratio for withdrawal was 2.4 (95% CI 1.4–4.0) indicating that a patient treated with CBZ was more than twice as likely to come off medication than one taking LTG. In conclusion, LTG can be regarded as an acceptable choice as initial treatment for elderly patients with newly diagnosed epilepsy.

Introduction

Old age is the commonest time to develop a seizure disorder (Tallis et al., 1991, Hauser, 1992, De la Court et al., 1996). More than 1% of 80 year olds and above have epilepsy. Around 25% of new cases of epilepsy occur in people over 60 years of age (Sander and Shorvon, 1996). No controlled clinical trials of antiepileptic drugs (AEDs) have been conducted in the elderly, despite the differences in drug handling and response in this population compared with younger patients (Willmore, 1998). Epilepsy in the elderly is often complicated by the presence of a range of medical disorders, for which other therapeutic agents may be prescribed. One of the standard treatments for newly diagnosed partial and tonic-clonic seizures is carbamazepine (CBZ) (Brodie and Dichter, 1997). This is also a preferred treatment for the elderly, although phenytoin (PHT) and sodium valproate (VPA) are also commonly used by geriatricians in the UK (Stolarek et al., 1995).

Lamotrigine (LTG), one of the newer AEDs, is licensed widely for partial and generalised seizures as add-on treatment and as monotherapy in adults and children (Dichter and Brodie, 1996). The drug has an elimination half-life exceeding 24 h and is metabolised in the liver largely by glucuronidation (Wilson and Brodie, 1996), a process largely unaffected by ageing (Posner et al., 1991). In a previous randomised double-blind study in adults with recent-onset epilepsy, no difference in efficacy was found between CBZ and LTG, while the latter was better tolerated (Brodie et al., 1995). A similar comparison has now been undertaken between LTG and CBZ in older people with newly diagnosed epilepsy.

Section snippets

Protocol

Patients aged 65 years and above with newly diagnosed epilepsy were allocated to double-blind treatment with LTG or CBZ, with LTG being allocated twice as often as CBZ. Treatment allocation was determined by a computer-generated random sequence, which was unknown to the investigators during the trial. It was planned to enrol 100 patients on LTG for the study, in keeping with the International Conference on Harmonisation (ICH) guidelines (1993) for studies in the elderly. Fifty additional

Results

A total of 150 patients were recruited (Table 2). Similar numbers were classified by the investigators as having idiopathic (LTG 41%, CBZ 31%), symptomatic (LTG 38%, CBZ 44%) and cryptogenic (LTG 21%, CBZ 25%) epilepsy. Thirty percent of the LTG and 38% of the CBZ group had had a previous cerebrovascular accident. The consort table for the study is illustrated in Table 3. The two patients who died while taking CBZ succumbed to a cerebrovascular accident and pneumonia respectively, neither of

Discussion

No controlled trials of AED therapy have been undertaken in an elderly patient population, despite the differences in drug handling and response between older and younger people (O’Mahoney and Woodhouse, 1994). There are a number of reasons why established AEDs, such as CBZ, PHT and VPA, might not be an ideal choice in the elderly, relating in particular to their propensity to cause neurotoxicity, idiosyncratic reactions, and pharmacokinetic interactions (Brodie and Dichter, 1996). In terms of

Acknowledgements

The investigators were: Dr S.N. Agnihotri, Royal Shrewsbury Hospital, Shrewsbury; Dr J.A. Anandadus, Altrincham General Hospital, Altrincham; Professor M.J. Brodie, Western Infirmary, Glasgow; Dr C.M. Byatt, Queen Elizabeth Hospital, King’s Lynn; Dr R.N. Corston, New Cross Hospital, Wolverhampton; Dr I.P. Donald, Gloucestershire Royal Hospital, Gloucester; Dr M. Ehsanullah, Lister Hospital, Stevenage; Dr G. Elrington, Severalls Hospital, Colchester; Dr T.A. Farnsworth, Castle Hill Hospital,

References (20)

  • M.J. Brodie et al.

    Established antiepileptic drugs

    Seizure

    (1997)
  • C.L. Read et al.

    Cognitive effects of anticonvulsant monotherapy in elderly patients: a placebo controlled study

    Seizure

    (1998)
  • L.J. Willmore

    Antiepileptic drug therapy in the elderly

    Pharmac. Ther.

    (1998)
  • Brodie, M.J., Richens, A., Yuen, A.W.C., and the UK Lamotrigine/Carbamazepine Monotherapy Trial Group, 1995....
  • M.J. Brodie et al.

    Antiepileptic drugs

    N. Engl. J. Med.

    (1996)
  • Brodie, M.J., Yuen, A.W.C., and the 105 Study Group, 1997. Lamotrigine substitution study: evidence for synergism with...
  • D.W. Chadwick et al.

    Serum anticonvulsant concentrations and the risk of drug-induced skin eruptions

    J. Neurol. Neurosurg. Psychiat.

    (1984)
  • Proposal for revised classification of epilepsy and epileptic syndromes

    Epilepsia

    (1989)
  • I. Craig et al.

    Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomised comparative study

    Epilepsia

    (1994)
  • A. De la Court et al.

    Prevalence of epilepsy in the elderly: the Rotterdam study

    Epilepsia

    (1996)
There are more references available in the full text version of this article.

Cited by (447)

View all citing articles on Scopus
View full text