title: Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade.
abstract: BACKGROUND
  It has been suggested that transiently high dopamine-2 (D(2)) receptor occupancy by antipsychotic medication may be sufficient for inducing an antipsychotic response. We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response.
  
  
  METHODS
  Fourteen patients with a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were treated with quetiapine titrated to a single daily dose (mean +/- SD dose at the time of the positron emission tomography [PET] scan = 427 +/- 69 mg) for 12 weeks. Peak D(2) occupancy approximately 2 hours postdose and trough D(2) occupancy approximately 20 hours postdose were determined using PET and [(11)C]raclopride. Clinical symptoms and side effects were measured at baseline and every 2 weeks during the treatment phase.
  
  
  RESULTS
  Quetiapine administration led to a mean peak D(2) occupancy of 62% +/- 10% 2 hours postdose, which declined to 14% +/- 8% approximately 20 hours postdose. Ten (71%) of 14 patients responded to treatment with quetiapine, scoring "much improved" or greater on the Clinical Global Impressions-Improvement scale. Plasma drug levels and peak D(2) occupancy were highly correlated (r = 0.84; p =.003), as were prolactin and plasma drug levels when measured 2.5 hours after drug administration (r = 0.60; p <.05). Mean weight gain for the 10 subjects who completed the 12-week study was 4.2 +/- 4.6 kg (9.3 +/- 10.2 lb). No clinically relevant motor side effects occurred during the trial.
  
  
  CONCLUSIONS
  Patients with a first episode of schizophrenia responded to treatment with a single daily dose of quetiapine despite only transiently high D(2) receptor occupancy. Our findings raise the question of whether continuously high D(2) blockade is necessary for obtaining an antipsychotic response. Future studies aimed at evaluating the relative merits of "transiently high" versus "continuously high" D(2) occupancy are warranted.
authors.affiliation: Schizophrenia and Continuing Care Program, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Sitra
authors.initials: S
authors.lastname: Tauscher-Wisniewski
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Johannes
authors.initials: J
authors.lastname: Tauscher
authors.forename: Corey
authors.initials: C
authors.lastname: Jones
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.forename: George
authors.initials: G
authors.lastname: Papatheodorou
authors.forename: Irvin
authors.initials: I
authors.lastname: Epstein
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Christensen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Zipursky
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002250:Carbon Radioisotopes; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D003987:Dibenzothiazepines; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D000069348:Quetiapine Fumarate; D020891:Raclopride; D011388:Prolactin