Prediction of early relapse after pimozide discontinuation by response to d-amphetamine during pimozide treatment

Thirteen schizophrenic patients underwent a d-amphetamine infusion while being treated with pimozide, an antipsychotic agent and a relatively specific dopamine (DA) blocker. Six patients who showed an acute increase in psychosis with d-amphetamine relapsed within 3 months after pimozide withdrawal. Of the seven patients who did not change in psychosis with d-amphetamine, six did not relapse after pimozide discontinuation (Fisher's exact test, p less than 0.005). Retrospectively, the psychosis-inducing effects of d-amphetamine were found to be predictive of psychotic exacerbation following subsequent pimozide withdrawal. Pimozide failed to block the psychotogenic effects of d-amphetamine in six patients indicating that other mechanisms besides DA may play a role in psychotic decompensation. The d-amphetamine infusion paradigm should be studied further to determine its clinical value for identifying which schizophrenic patients are at risk for relapse after discontinuation of neuroleptic treatment.