Effects of Antiepileptic Drugs and Seizure Type on Operant Responding in Mentally Retarded Persons

Abstract

The performance of 129 mentally retarded persons was studied on a progressive fixed-ratio schedule of reinforcement. Subjects were selected according to antiepileptic drug (AED) regimen or membership in one of four control groups. The AEDs studied were: phenobarbital (PB); phenytoin (PHT); PB in combination with PHT (PB/PHT); and valproic acid (VPA) in combination with other AEDs . The control groups were: persons without seizure disorders and on no medications (control); persons without seizure disorders, but on the chronic medication thioridazine ( TDZ ); persons with histories of one or more seizures and treatment with PB and/or PHT, but currently on no AEDs ; and, to control for the effects of multiple AEDs , persons on multiple drug regimens (i.e., PB and/or PHT in combination with carbamazepine and/or ethosuximide). Except for the VPA group, response rates per minute were decreased in high intelligence quotient (greater than 40) persons receiving AEDs or with a history of treated seizures. Deficits in responding were particularly marked in persons with partial seizures. Persons on VPA responded at rates comparable with those of the control and TDZ groups, unless they had partial seizures. This effect was independent of seizure frequency and was inversely related to serum level. Persons on PB most frequently exhibited frustration responses during testing, and when these occurred they were rated as being significantly more severe. Persons on PB also most frequently elected to "leave the experiment" and did so primarily for reasons thought to reflect deficits in inhibition. These results suggest that operant tasks can be sensitive to both AED effects and to underlying alterations of function that accompany seizure disorders in the mentally retarded.