An Experimental Study on the Influences of Psychotropic Drugs Upon Cardiac Function

Abstract

It is known that the majority of patients under the treatment with potent psychotropic drugs present more or less altered electrocardiograms aside from their clinical significance. On the other hand, the incidence of sudden death during the drug therapy has become the object of public attention since several years. For the purpose of working out a possible solution of these problems, the author has studied the influences of psychotropic drugs upon cardiac function electrocardiographically in male rats of Sprague Dawley breed.
As experimental drugs, the author picked up four compounds as follows: Reserpine (2.5 & 5.0mg/kg/s. c. /day), which has long been one of the leading neuroleptic drugs; thioridazine (50,100,200 & 300mg/kg/p. o. /day), which has been frequently accused of the highest incidence of sudden death; carpipramine (50,100,200 & 300mg/kg/p. o. /day), which has been widely used not as thymoleptic but as anti-psychotic agent inspite of being an iminodibenzyl derivative; and clocapramine (50,100,200 & 300mg/kg/p. o. /day), which has been recently marketed as a safer drug than carpipramine. Throughout the experiment, general conditions of rats were surveyed daily and electrocardiograms derived from limbs were recorded on magnetic tape weekly. After completing the planned medication, a series of laboratory examinations and pathological investigations were made on animals in order to find abnormalities which might be responsible to electrocardiographic alterations. All the electrocardiograms on tape were played back later and analyzed digitally using ATAC-501-20 medical biopotential data processor. Thus, the author has been convinced that all the measurements were the most accurate among the methods available today.
The influence of reserpine upon electrocardiogram seemed to be completely different from those of the other three compounds. It induced marked prolongation and irregularization of R-R and P-R as well as early depression of T. The prolongation of R-R appeared on the third day of experiment. In the contrary, the influences of the other compounds showed many similarities in provoking marked prolongation of QRS and Q-T associated with an elevation of T instead. The results can be interpreted that reserpine affects mainly the impulse generating system and the atririoventricular conduction while the other three compounds impair the repolarization and intraventricular conduction.
After six weeks, the administration of compounds was discontinued in several animals of thioridazine and carpipramine groups in order to observe possible recovery from the cardiac dysfunctions induced by the drugs. In thioridazine group the recovery has been noted immediately after one week, but in carpipramine group the augmentation of electrographical alterations lasted for another two weeks before signs of recovery have been found. However, these facts suggest that the cardiac dysfunctions or the electrocardiographic alterations caused by psychotropic medication may be reversible unless it is too late to stop the medication.
Laboratory examinations have shown no particular abnormality which may correspond to the induced alterations of electrocardiograms. By the way, there was not any reduction of serum K enough to explain the prolongation of Q-T or the elevation of T. Pathohistological investigations of hearts have revealed myocardiac atrophy, degeneration and/or cell infiltration in a few animals.