Review of serum prolactin levels as an antipsychotic‐response biomarker

Abstract

Antipsychotics acting as antagonists at dopamine D2 receptors concentrated in the striatum are the cornerstone of effective treatment of psychosis. Substantial progress in treating persons with schizophrenia could be achieved by the identification of biomarkers which reliably determine the lowest efficacious dose of antipsychotics. Prolactin levels have been considered a promising treatment-response biomarker due to dopamine's regulation of serum prolactin levels through D2 receptors in the hypothalamic-pituitary pathway. Prolactin secretion in response antipsychotic administration is associated with the antipsychotics affinity for D2 receptors. This review assesses the available literature on the use of serum prolactin levels as an antipsychotic-response biomarker. Articles were identified through PubMed as well as the reference lists of full text articles available online. Relevant publications were summarized briefly to define the limitations and utility of serum prolactin levels as a tool for improving antipsychotic dosing. Serum prolactin levels in combination with prolactin-inducing potencies for each antipsychotic may help identify the lowest effective dose of antipsychotic medications. , In addition to the fact that prolactin secretion is dependent on serum antipsychotic levels and not brain levels, recent findings show that prolactin release is independent of the β-arrestin-2 pathway and GSK3β regulation, one branch of the pathway that has been implicated in antipsychotic efficacy. Therefore, serum prolactin is an indirect biomarker for treatment response. Further investigations are warranted to characterize prolactin-antipsychotic dose-response curves and systematically test the utility of measuring prolactin levels in patients to identify a person's lowest efficacious dose.

Antipsychotics-induced hyperprolactinemia and screening for macroprolactin

“…Patients with or without symptoms of HPRL may have high serum prolactin (PRL) concentrations, but prevalence rates and degrees of severity of HPRL may differ depending on the affinity of the antipsychotic drugs for D2 receptors, different penetrability across the blood-brain barrier and the modulation of monoamines other than dopamine ( 5 ).…”

Clozapine-Associated Hypersexuality

“…5 More specifically, D 2 antagonists reduce dopaminergic neurotransmission in the tuberoinfundibular dopamine pathway by blocking dopamine D 2 receptors and mediating the mesolimbic circuit in the hypothalamus-pituitaryadrenal axis. 9 Physiological processes are associated with a surge in serum prolactin levels, which is associated with sexual dysfunction. 7,9 In our case, the transition from antipsychotics with higher dopamine D 2 receptor affinity, including risperidone and amisulpride, to clozapine might have been associated with rebalancing dopamine D 2 receptor occupancy and less suppression of the mesolimbic circuit and tuberoinfundibular dopamine pathway, leading to reduced libido inhibition.…”

“…5 More specifically, D 2 antagonists reduce dopaminergic neurotransmission in the tuberoinfundibular dopamine pathway by blocking dopamine D 2 receptors and mediating the mesolimbic circuit in the hypothalamus–pituitary–adrenal axis. 9 Physiological processes are associated with a surge in serum prolactin levels, which is associated with sexual dysfunction. 7,9…”

Risperidone Induced Hyperprolactinemia: From Basic to Clinical Studies

“…Blockade leads to loss of inhibitory factor dopaminergic prolactin in lactotrophic cells. Which explains the fact that APs with a higher D2 binding index produce a larger and more frequent increase in prolactin (38,39).…”