Synopsis: Pimozide¹ 1-(1-[4,4-bis(4fluorophenyl)butyl]-4-piperidinyl)-2-benzimidazolone, is the first of a new series of psychotropic drugs, the diphenylbutylpiperidines. It is advocated for once-daily use as maintenance therapy in chronic schizophrenia and for the treatment of psychic and functional disorders induced by personality traits.

Published data suggest that in chronic schizophrenia, pimozide 4 to 6mg daily is indistinguishable from maintenance doses of chlorpromazine, fluphenazine, flupenthixol, perphenazine, or thioridazine. Patient groups have usually been too small to allow statistically significant differences to be apparent, but in some trials pimozide was significantly superior to trifluoperazine and to haloperidol. On present evidence, pimozide has no place in the hyperactive, aggressive type of patient or in treating the acute phase of schizophrenia, probably because of its relative lack of sedative properties compared with many anti-psychotic drugs. The incidence and severity of extrapyramidal reactions with pimozide are low, but suitably designed controlled studies are needed to determine whether its use leads to a reduction in the requirement for antiparkinsonian medication. In anxious patients, pimozide seems to offer no advantages over currently available anxiolytic agents, either in terms of efficacy or incidence of side-effects. Claims for a specific effect against anxiety associated with psychosis or disturbed personality traits remain unproven.

Pharmacodynamic studies have demonstrated significant and prolonged central nervous system activity following oral and subcutaneous administration to animals in a variety of laboratory tests. Pimozide was found to possess typical neuroleptic properties with a profile more akin to that of haloperidol than chlorpromazine. It was typically slower in onset but longer in duration of action than either comparison drug in tests which included production of catalepsy or palpebral ptosis, and inhibition of shock avoidance or intracranial self-stimulation reactions. Like other neuroleptics, pimozide antagonises many of the actions of amphetamine and apomorphine, such as stereotyped behaviour and emesis, but it is not so effective as haloperidol or chlorpromazine in protecting animals against lethal doses of noradrenaline. It seems to be a specific blocker of central dopamine receptors, increasing turnover of brain dopamine but not noradrenaline. Pimozide causes a gradual decrease in food consumption and corresponding inhibition of weight gain in young animals. No dysmorphogenic or embryotoxic effects have been noted in long-term toxicity studies, though high-dose regimens have produced some incidences of mammary gland stimulation, prolonged anoestrus, follicular atresia and gingival hyperplasia. No significant alterations in cardiovascular haemodynamics have been observed after pimozide, and the drug has minimal activity on the autonomic nervous system.

In man, the pharmacological effects of pimozide are essentially those affecting the central nervous system. High oral doses of 20mg daily were not well accepted by normal prison volunteers, requests for removal from the study coming from days 16 to 20 because of nervousness, restlessness, insomnia, drowsiness, listlessness, and fatigue. Maintenance doses in psychotic patients have failed to produce a similar incidence. In chronic schizophrenic patients, desynchronisation of the EEG is decreased, together with enhanced α-index (cortical activation), in those patients showing positive clinical response. There is still some dispute, however, as to whether the EEG effects of pimozide differ or are …