Trimethadione: Its Dosage and Toxicity

Abstract

In the decade during which trimethadione (Tridione) has been in wide clinical use it has proved to be an excellent therapeutic agent for the treatment of the petit mal triad. The petit mal triad is manifested by episodes of absence, akinesis, and myoclonic jerks (occurring singly or together in a given patient), with the electroencephalogram showing characteristic 3-per-second spike-and-wave discharges, bilaterally symmetrical and most prominent anteriorly. It is proposed that its therapeutic usefulness can be successfully and materially extended by the vigorous usage of this medication in doses considerably higher than those generally employed. The following three cases illustrate its effectiveness when used in this manner. Report of CasesCase 1.*\p=m-\Twenty-year-oldyouth; weight, 55.7 kg. (122.5 lb.).Nothing is known of the patient's birth and early development. He began having seizures at about the age of 5 or 6 years. He had no warning or aura. Seizure types: 1. The majority of the seizures consisted of a brief loss of contact with the environment lasting less than a minute, accom¬ panied by nodding of the head, blinking of the eyes, and swaying of the trunk. He generally did not fall with such attacks. Following such an episode, he felt somewhat confused and dazed for a few seconds. 2. Less frequently he had at¬ tacks in which he would abruptly fall to the floor without warning and remain unconscious for 30 to 40 minutes. He had been told that there were shaking movements of the extremities with these case and made many helpful suggestions concerning the preparation of this manuscript.episodes, but tongue biting and incontinence did not occur. On admission to the Clinical Center of the National Institutes of Health, the patient was having an average of 20-40 seizures of the first type daily (with occasionally as many as 80 to 100 in a single day) and about 1 of the second type every two weeks.Prior to admission the patient had been tried, with no appreciable degree of success, on the fol¬ lowing medications (with maximal doses listed) : phénobarbital 0.1 gm/day, diphenylhydantoin (Dilantin) sodium 0.5 gm/day, trimethadione (Tridione) 1.2 gm/day, methylphenylethyl hydantoin (Mesantoin) 0.4 gm/day, primidone (Mysoline) 2.25 gm/day, glutamic acid 2.4 gm/day, and phensuximide (Milontin) 2.0 gm/day. The follow¬ ing combinations are known to have proved inef¬ fective ; phénobarbital 60 mg/day and diphenylhy¬ dantoin sodium 0.4 gm/day ; phénobarbital 60 mg/day and trimethadione 0.9 gm/day ; diphenyl¬ hydantoin sodium 0.5 gm/day, methylphenylethyl hydantoin 0.4 gm/day, and phénobarbital 0.1 gm/day; primidone 1.0 gm/day, trimethadione 1.2 gm/day, diphenylhydantoin sodium 0.4 gm/day, and glutamic acid 2.4 gm/day; primi¬ done 1.5 gm/day, phensuximide 1.0 gm/day, and phénobarbital 0.09 gm/day. Personality problems, in the form of temper tantrums, irritability, and occasionally hostility and destructiveness, had oc¬ curred with periods of especially severe seizure activity.On admission, the patient was well developed, w...

Drug treatment of epilepsy in the century of the ILAE: The first 50 years, 1909–1958

“…The rosy picture of medical progress was clouded, however, by reports of nephrotic syndrome (Barnett et al., 1948), renal failure, fatal dermatitis, and fatal blood dyscrasia (Denhoff & Laufer, 1950). The nephrotic syndrome was usually reversible, although two fatalities had been recorded by 1957 (Wells, 1957). In 1947, within a year of the introduction of the drug, two deaths from aplastic anaemia were reported—and by 1957, a further 11 had been recorded (Wells, 1957).…”

“…The nephrotic syndrome was usually reversible, although two fatalities had been recorded by 1957 (Wells, 1957). In 1947, within a year of the introduction of the drug, two deaths from aplastic anaemia were reported-and by 1957, a further 11 had been recorded (Wells, 1957). Davis and Lennox (1947) found neutropenia (white blood cell count <2,500/cm 3 ) in 6.3% of 222 patients.…”

Frontmatter

“…The rosy picture of medical progress was clouded however by reports of nephrotic syndrome [60], renal failure, fatal dermatitis and fatal blood dyscrasia [61]. The nephrotic syndrome was usually reversible, although two fatalities had been recorded by 1957 [62]. In 1947, within a year of the introduction of the drug, two deaths from aplastic anaemia were reported -and by 1957, a further 11 had been recorded [62].…”

“…The nephrotic syndrome was usually reversible, although two fatalities had been recorded by 1957 [62]. In 1947, within a year of the introduction of the drug, two deaths from aplastic anaemia were reported -and by 1957, a further 11 had been recorded [62]. Davis and Lennox [63] found neutropenia (white count less than 2500/cm 3 ) in 6.3% of 222 patients.…”

The New Drugs and the Strategies to Manage Epilepsy

“…Trimetadione, Phenobarbital and Primidone (PMD) are used less and less due to their toxic effects [3][4][5].…”