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.
Psychiatry Service, New York VA Medical Center, New York.
A
A
Wolkin
E
E
Duncan
M
M
Sanfilipo
S
S
Wieland
T B
TB
Cooper
J
J
Rotrosen
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D004351:Drug Resistance; D004357:Drug Synergism; D005625:Frontal Lobe / Q000503:physiopathology; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D017211:Treatment Failure; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D014150:Antipsychotic Agents; D008781:Methyltyrosines; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid