Diphenylhydantoin Serum Levels, Toxicity, and Neuropsychological Performance in Patients with Epilepsy

Abstract

The neuropsychological effects of diphenylhydantoin were assessed in 70 adults having primarily psychomotor and major motor seizures. All patients were stabilized on diphenylhydantoin alone, and assessment of this drug by gas-liquid chromatography provided a basis for dichotomizing the group into High and Low drug groups, both with and without toxic patients. In addition, patients showing signs of toxicity were contrasted with those not showing such signs. In each of these comparisons, control was maintained with respect to the variables of age, education, age at onset of disorder, and duration of disorder. Neuropsychological assessment was by means of the test battery originated by Halstead and developed by Reitan. Results showed that the High and Toxic Groups rather consistently did more poorly on all tasks than the Low and Nontoxic Groups. However, differences which were statistically significant appeared only in connection with tasks which had a heavy motor component. Possible reasons for the lack of statistically significant differences on the higher level mental tasks were presented.

Sodium valproate and cognitive functioning in normal volunteers.

“…Although the observed decrements in the present investigation may well reflect only transient impairment of functioning, evidence from other work, especially involving phenytoin, suggests that this is not the case, adverse effects having been recorded with more prolonged use (Dodrill, 1975;Dodrill & Troupin, 1977;Trimble & Corbett, 1980) and, conversely, improvements following its withdrawal (Rosen, 1968;Nolte et al, 1980;Thompson, in preparation). Thus while the majority of reports of sodium valproate mentioned earlier, especially if anecdotal impressions are included, suggest a beneficial effect of this drug in patients with epilepsy it is possible these observed improvements may be an indirect consequence of other variables such as better seizure control or withdrawal of other medications which had previously been exerting a detrimental influence, rather than to an independent psychotropic effect per se.…”

Anticonvulsant Activity of PNU‐151774E1 in the Amygdala Kindled Model of Complex Partial Seizures

“…The differences between therapeutic and active doses in various models are important, especially as clinically used AEDs develop undesirable side effects, in particular when exceeding therapeutic plasma concentrations (e.g., 28). For example, both LTG (29) and PHT (30) have been shown to impair cognition, and this impairment is related to their concentrations in the plasma.…”

Anticonvulsant serum levels: relationship to impairments of cognitive functioning.

“…' Therapeutic ranges have been established for several anticonvulsants within which maximum seizure control may be expected with minimum occurrence of side effects, such as nystagmus, ataxia, diplopia and mental confusion.2 However, it is unclear whether serum level monitoring may also prove useful for avoiding detrimental drug-induced changes in cognitive functioning which have been reported.3 In the assessment of the effects of these drugs on cognition only a few investigators have included measurements of anticonvulsant serum concentrations and several have reported impairments in association with high but not always toxic levels. [4][5][6][7][8][9] The majority of studies have either compared the psychological test performance of two groups of patients, divided about some arbitrary cut-off value into high and low serum groups,56 or have correlated psychological test scores of a sample of patients with their individual serum concentrations.8 9 Interpretation of the findings from such studies unfortunately is complicated since many interrelated factors such as seizure severity and frequency, head traumas and psychosocial problems have been implicated as influencing the cognitive state of patients with epilepsy. '0 Patients with high anticonvulsant serum levels may well differ with respect to a number of such important parameters from patients with lower serum concentrations.…”