title: Striatal dopaminergic D2 receptor occupancy and clinical efficacy in psychosis exacerbation: a 123I-IBZM study with ziprasidone and haloperidol.
abstract: OBJECTIVE
  The aim of this study was to compare striatal dopaminergic D2 receptor occupancy (D2 RO) induced by ziprasidone and haloperidol and its relationship with clinical response and extrapyramidal side effects (EPS) in patients with acute psychosis exacerbation.
  
  
  METHODS
  Twenty patients hospitalized with an acute psychosis exacerbation were randomised in a single-blind study to receive either ziprasidone (80-120 mg/day) or haloperidol (5-20 mg/day) for more than 2 weeks. When stable doses were achieved, data on 123I-IBZM single-photon emission computed tomography (SPECT), as well as data on clinical efficacy (positive and negative symptoms scale [PANSS]) and EPS (Simpson Angus scale [SAS]), were compared between the two groups of patients. Clinical response was defined as a percentage of change of >30% in PANSS. Striatal D2 RO and clinical data were also compared between responders and nonresponders on each treatment group.
  
  
  RESULTS
  All patients on haloperidol and four patients on ziprasidone showed EPS. Mean D2 RO was significantly higher in the haloperidol (74.7+/-3.5) than in the ziprasidone (60.2+/-14.4) group (Mann Whitney U-test [M-W U-test] 8.50; p=0.002). Five patients were responders, and five were nonresponders on each group of treatment. Haloperidol responders and nonresponders did not differ in D2 RO, duration of treatment, doses or EPS. Ziprasidone responders were on higher doses than nonresponders and showed higher D2 RO although below 74%. A positive correlation of ziprasidone D2 RO was found with dose (r Spearman 0.87; p=0.001) and with SAS scores (r Spearman 0.88; p=0.001).
  
  
  CONCLUSIONS
  Ziprasidone induces lower D2 RO and EPS than haloperidol, which is consistent with an atypical antipsychotic profile. A direct relationship of ziprasidone D2 RO with dose, clinical efficacy and EPS has been found in this study. These data suggest that high ziprasidone doses might be more beneficial in patients with psychosis exacerbation and claim for caution regarding EPS appearance with such high dosages.
authors.affiliation: Department of Psychiatry, Hospital de la Sta. Creu i St. Pau, Autonomous University of Barcelona (UAB) [corrected] Sant Antoni Maria Claret 167 08025 Barcelona, Spain. icorripio@hsp.santpau.es
authors.forename: Iluminada
authors.initials: I
authors.lastname: Corripio
authors.forename: Ana M
authors.initials: AM
authors.lastname: Catafau
authors.forename: Víctor
authors.initials: V
authors.lastname: Perez
authors.forename: Dolors
authors.initials: D
authors.lastname: Puigdemont
authors.forename: Esther
authors.initials: E
authors.lastname: Mena
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Aguilar
authors.forename: Ignasi
authors.initials: I
authors.lastname: Carrió
authors.forename: Enric
authors.initials: E
authors.lastname: Alvarez
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004351:Drug Resistance; D004409:Dyskinesia, Drug-Induced / Q000523:psychology; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D016037:Single-Blind Method; D013844:Thiazoles / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D017211:Treatment Failure
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D010879:Piperazines; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D013844:Thiazoles; C092292:ziprasidone; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D006220:Haloperidol