Instrumentally detected changes in motor functioning in patients with low levels of antipsychotic dopamine D2 blockade.
Extrapyramidal side-effects (EPSE) of antipsychotic medication are related to the occupancy of dopamine D2 receptors and there appears to be a threshold of D2 occupancy below which clinically EPSE are unlikely to occur. It is unclear whether there are motor changes produced by 'subthreshold' levels of D2 occupancy that are not detectable by clinical examination. This study was designed to investigate whether a number of electromechanical instrumental techniques could detect 'subthreshold' motor changes and whether these changes correlate with dopamine D2 occupancy as measured by [11C]-raclopride PET scan. Twenty medication naïve patients were studied before and during treatment with low dose haloperidol. Instrumental techniques detected an asymmetrical worsening in motor function with drug treatment despite the failure of the group to experience significant EPSE. These changes did not correlate with D2 occupancy and measurements of rigidity, tremor, and bradykinesia did not closely inter-correlate.
Fitzgerald
P B
PB
Dandenong Psychiatry Research Unit & Dandenong Area Mental Health Service, Victoria, Australia.
Kapur
S
S
Caligiuri
M P
MP
Jones
C
C
Silvestri
S
S
Remington
G
G
Zipursky
R B
RB
D000328:Adult; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006220:Haloperidol / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D018476:Hypokinesia; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009127:Muscle Rigidity; D020891:Raclopride / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D012563:Schizophrenia, Paranoid / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D014055:Tomography, Emission-Computed; D014202:Tremor
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride; D006220:Haloperidol