Persistent psychosis after reduction in pre- and post-synaptic dopaminergic function.

The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of "adequate" DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent.