Threshold of dopamine D2/3 receptor occupancy for hyperprolactinemia in older patients with schizophrenia

Yusuke Iwata, Shinichiro Nakajima, Fernando Caravaggio, Takefumi Suzuki, Hiroyuki Uchida, Eric Plitman, Jun Ku Chung, Wanna Mar, Philip Gerretsen, Bruce G. Pollock, Benoit H. Mulsant, Tarek K. Rajji, David C. Mamo, Ariel Graff-Guerrero

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6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e1557-e1563
JournalJournal of Clinical Psychiatry
Volume77
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

ASJC Scopus subject areas

  • Psychiatry and Mental health

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    Iwata, Y., Nakajima, S., Caravaggio, F., Suzuki, T., Uchida, H., Plitman, E., Chung, J. K., Mar, W., Gerretsen, P., Pollock, B. G., Mulsant, B. H., Rajji, T. K., Mamo, D. C., & Graff-Guerrero, A. (2016). Threshold of dopamine D2/3 receptor occupancy for hyperprolactinemia in older patients with schizophrenia. Journal of Clinical Psychiatry, 77(12), e1557-e1563. https://doi.org/10.4088/JCP.15m10538