Long term use of lamotrigine and vigabatrin in severe refractory epilepsy: audit of outcomeBMJ 1996; 313 doi: https://doi.org/10.1136/bmj.313.7066.1184 (Published 09 November 1996) Cite this as: BMJ 1996;313:1184
- a Epilepsy Research Group, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London WC1N 3BG
- b National Society for Epilepsy, Chalfont St Peter, Buckinghamshire SL9 0RJ
- c Epilepsy Group, Montreal Neurological Institute, 3801 Rue Universite, Montreal, Quebec, Canada H3A 2B4
- Correspondence to: Dr Walker.
- Accepted 18 March 1996
New antiepileptic drugs have a pivotal role in the successful treatment of the 20–30% of patients with epilepsy that is resistant to drug treatment. They are considered to be effective in such patients if they reduce the frequency of seizures by 50% or more because few patients are rendered seizure free.1 Despite these drugs' apparent success with this outcome measure,2 3 the question still remains whether new antiepileptic drugs affect the long term prognosis of refractory epilepsy as measured by mortality and freedom from seizures.1 We report our follow up audit of patients recruited from 1987 to 1989 into two uncontrolled open label clinical studies of lamotrigine and vigabatrin.2 3
Patients, methods, and results
The two open label trials in 128 patients (vigabatrin) and 125 patients (lamotrigine) were both described in detail in 1990.2 3 All patients had confirmed severe medically refractory epilepsy and were evaluated as inpatients or outpatients at the Chalfont Centre for Epilepsy or the National Hospital for Neurology and Neurosurgery. After the trials the patients could continue the trial drugs, which were licensed in 1989 (vigabatrin) and 1991 (lamotrigine). By using hospital records and by contacting general practitioners, referring physicians, and the patients directly, we determined (a) how many patients were free of seizures, (b) how many were still taking the trial drug, and (c) how many had died. When appropriate the data on lamotrigine and vigabatrin were compared with the χ2 test.
We successfully followed up 120 (96%) and 124 (97%) of the patients in the vigabatrin and lamotrigine trials respectively. Four of the five lost to follow up in the lamotrigine group and two of the four lost to follow up in the vigabatrin group were no longer taking their respective trial drug. Table 1 shows details of the patients. A total of 16 (13%) of the lamotrigine group and 13 (10%) of the vigabatrin group had died in about 850 patient years. Of those living, 89 (86%) of the lamotrigine group and 96 (86%) of the vigabatrin group were no longer taking their respective trial drug, although 26 (21%) of the lamotrigine group and 41 (31%) of the vigabatrin group had responded to treatment. One patient was seizure free while taking lamotrigine and two were seizure free while taking vigabatrin. There were no significant differences at P<0.05 between the lamotrigine and vigabatrin groups.
Of those successfully followed up 6–8 years after recruitment into open label trials for vigabatrin and lamotrigine, three patients were rendered seizure free. Indeed, 86% of those still living were no longer taking the trial drugs; this was probably due to inefficacy or intolerance. However, there may be confounding factors such as withdrawal of the treatment after successful surgery for epilepsy or after entry of patients into other drug trials.
The high death rates that we observed of about 15 per 1000 patient years for vigabatrin and 19 per 1000 patient years for lamotrigine are comparable with the high mortality of 13–33 per 1000 patient years in this population.4 5
Thus the addition of either vigabatrin or lamotrigine to the treatment of a particularly refractory type of epilepsy has only marginal benefit in terms of mortality and freedom from seizures. These drugs may be more beneficial in less refractory epilepsy or in different patient groups, and they may prove to have fewer adverse effects than older antiepileptic drugs. However, new antiepileptic drugs are developed to improve the prognosis of severe refractory epilepsy, and we should not deceive ourselves that this task has been accomplished.
We thank Ian Wong for help in gathering patient information, and the Wellcome Trust for supporting the work of MCW.
Conflict of interest None.