Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia

J Clin Psychiatry. 2016 Dec;77(12):e1557-e1563. doi: 10.4088/JCP.15m10538.

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.

Trial registration: ClinicalTrials.gov identifier: NCT00716755.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Dopamine Antagonists*
  • Female
  • Humans
  • Hyperprolactinemia / chemically induced*
  • Male
  • Middle Aged
  • Olanzapine
  • Positron-Emission Tomography / methods*
  • Prolactin / blood*
  • Raclopride
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Risperidone / administration & dosage
  • Risperidone / adverse effects*
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • DRD2 protein, human
  • DRD3 protein, human
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Benzodiazepines
  • Raclopride
  • Prolactin
  • Risperidone
  • Olanzapine

Associated data

  • ClinicalTrials.gov/NCT00716755