title: Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia.
abstract: OBJECTIVE
  Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels.
  
  
  METHODS
  The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests.
  
  
  RESULTS
  Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers.
  
  
  CONCLUSIONS
  Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00716755.
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.|Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.|Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Wanna
authors.initials: W
authors.lastname: Mar
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.|Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.|Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.|Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.|Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Department of Psychiatry, Faculties of Medicine and Health Science, University of Malta, Msida.
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R, Canada. ariel_graff@yahoo.com.mx.|Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada.|Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D049268:Positron-Emission Tomography / Q000379:methods*; D011388:Prolactin / Q000097:blood*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D001569:Benzodiazepines; D020891:Raclopride; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine