Correspondence

Felbamate Therapy in the Lennox-Gastaut Syndrome

N Engl J Med 1993; 328:1641June 3, 1993

Article

To the Editor:

The modest decrease in the numbers of parent-reported seizures in children receiving felbamate (Jan. 7 issue)1 is encouraging, but the results were disappointing in several respects.

The frequency of seizures during the base-line period was greater in the felbamate group than in the placebo group. Some of the improvement in the felbamate group could therefore have been due to regression to the mean. This possibility would be supported by a correlation between the base-line frequency of seizures and the decrease in seizures during treatment. The number of seizures recorded during the videotelemetry sessions was similar in the felbamate and placebo groups. Felbamate often caused somnolence; nearly half of the patients had this side effect. How many of the patients treated with felbamate who were seizure-free during videotelemetry were seizure-free six months later? An unsustained response is of limited value.

Although improved global-rating scores suggest better function, I would like to know the magnitude of that change, which apparently was not found until day 49. Global ratings should be supplemented by specific data. Was there a change in the number of hours slept per day or in the number of school days missed? What about teachers' ratings? What is the basis for the statement that the patients treated with felbamate had increased alertness and verbal responsiveness?

The analysis should also consider interactions between felbamate and other drugs. Perhaps felbamate often benefits patients taking one type of drug and rarely benefits patients taking another type of drug. Patients with the Lennox-Gastaut syndrome receive many different drugs, and information about interactions between felbamate and valproate, phenytoin, and other anticonvulsant drugs would be of interest.

S. Robert Snodgrass, M.D.
University of Mississippi Medical Center, Jackson, MS 39216

1 References

1
The Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med 1993;328:29-33
Full Text | Web of Science | Medline

Author/Editor Response

Dr. Ritter replies:

To the Editor: The mean numbers of seizures during the base-line period were greater in the felbamate group than in the placebo group, but not significantly so. Seizure counts tend to have asymmetrical distributions, and it is not unusual to find a few high values in any group of patients. There was no correlation between the base-line frequency of seizures and the amount of improvement in the patients treated with felbamate; the rank-correlation coefficient measuring this relation was 0.05. Visual inspection of the data indicated that many patients with low base-line seizure counts had the same degree of improvement as those with higher counts.

The lengths of the episodes of somnolence varied, and most resolved spontaneously or with changes in the dose of felbamate or the concomitantly administered antiepileptic drugs. These results suggest that the relatively high incidence of somnolence was due to drug interactions between felbamate and standard antiepileptic drugs. The incidence of somnolence in patients treated with felbamate alone was substantially lower1.

It should be emphasized that the seizures in patients with the Lennox-Gastaut syndrome are generally unresponsive to treatment and that the patients studied in this trial had received an average of eight antiepileptic drugs before the trial, none of which controlled the seizures. It is impressive, therefore, that four patients had no seizures during the 56-day maintenance period. Seventy-five percent of the 73 patients in this trial have since been treated with felbamate for more than 1 year (mean, 22 months). Seven of 13 patients treated for up to 12 months at one center had at least a 50 percent reduction in the frequency of seizures2. At another center, 12 of 16 patients treated for 25 to 39 months had a mean reduction of 56 percent in the frequency of seizures3. These data indicate that the therapeutic effect of felbamate is sustained.

The improvement in global-evaluation scores was significant on study day 49, which was the 21st day of felbamate therapy. The global evaluations were based on the parents' or guardians' impressions of the patient's quality of life with respect to alertness, verbal responsiveness, general well-being, and seizure control. More specific measures, such as the number of hours slept or school performance, would have been reflected in the general assessement of the quality of life. The statement regarding increased alertness and verbal responsiveness was based on the global-evaluation scores.

The patients we studied were treated with many different combinations of standard antiepileptic drugs in addition to felbamate. Not enough patients took any one combination to allow comparisons to be made with regard to an effect on the efficacy of felbamate.

Frank J. Ritter, M.D.
Minnesota Epilepsy Group, St. Paul, MN 55102

3 References

1
Sachdeo RS, Kramer LD, Rosenberg A, Sachdeo S. Felbamate monotherapy: controlled trial in patients with partial onset seizures. Ann Neurol 1992;32:386-392
CrossRef | Web of Science | Medline

2
Garofalo EA, Olson LD, Sackellares JC, Komarynski MA, Tornow MA, Tripathi A. Lennox-Gastaut syndrome: treatment of seizures with felbamate. Ann Neurol 1991;30:492-492 abstract.
Web of Science

3
Espe-Lillo J, Ritter FJ. Long-term follow-up of felbamate treatment in children with Lennox-Gastaut Syndrome. Epilepsia 1992;33:Suppl 3:118-118 abstract.

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