title: Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol.
abstract: BACKGROUND
  Extrapyramidal symptoms (EPS) are common with conventional antipsychotics. Clozapine and other novel antipsychotic substances with lower in vitro affinity for dopamine-2 (D(2)) receptors have a lower propensity to induce EPS.
  
  
  OBJECTIVE
  We investigated whether striatal D(2) receptor occupancy predicted the occurrence of EPS with atypical antipsychotics and the typical neuroleptic haloperidol.
  
  
  METHODS
  [(123)I]Iodobenzamide (IBZM) and single photon emission tomography (SPECT) were used to quantify receptor occupancy in 71 patients treated with antipsychotics. EPS were rated according to the Simpson-Angus scale (SAS). EPS were deemed clinically relevant, if the SAS score was > or = 5 and/or anticholinergic medication was required. Patients received atypical antipsychotic monotherapy for at least 14 days with amisulpride ( n=2), clozapine ( n=6), haloperidol ( n=10), olanzapine ( n=6), quetiapine ( n=4), risperidone ( n=14), sertindole ( n=13), or zotepine ( n=16).
  
  
  RESULTS
  The striatal D(2) receptor occupancy ranged from < 20% to almost saturation. The lowest occupancy was seen with quetiapine and clozapine, the highest with haloperidol. Twenty-two of 71 patients (29%) experienced clinically relevant EPS. These patients displayed significantly higher mean striatal D(2) receptor occupancy (77%) than those without EPS (61%; P=0.002). We found a positive correlation between the percentage of striatal D(2) receptor occupancy and the SAS score ( r=0.28; P=0.02), despite 18 of these patients receiving anticholinergics, thus lowering their SAS score.
  
  
  CONCLUSIONS
  Striatal D(2) receptor occupancy as measured with [(123)I]IBZM and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. In vivo imaging of brain receptors with SPECT may provide a useful clinical tool to titrate doses individually and avoid motor side effects in patients treated with novel antipsychotics.
authors.affiliation: Department of General Psychiatry, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. johannes.tauscher@akh-wien.ac.at
authors.forename: Johannes
authors.initials: J
authors.lastname: Tauscher
authors.forename: Bernd
authors.initials: B
authors.lastname: Küfferle
authors.forename: Susanne
authors.initials: S
authors.lastname: Asenbaum
authors.forename: Sitra
authors.initials: S
authors.lastname: Tauscher-Wisniewski
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism; D005260:Female; D005544:Forecasting; D006220:Haloperidol / Q000009:adverse effects*; D006801:Humans; D007462:Iodobenzenes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009127:Muscle Rigidity / Q000139:chemically induced; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D007462:Iodobenzenes; D017448:Receptors, Dopamine D2; C426805:idobenzamide; D006220:Haloperidol