title: Impact of different antidopaminergic mechanisms on the dopaminergic control of prolactin secretion.
abstract: Antipsychotics are the most common cause of pharmacologically induced hyperprolactinemia. Although this adverse effect was the subject of numerous observations, the mechanisms and promotive factors were not completely investigated yet. Increased awareness of clinical consequences of hyperprolactinemia implicates the necessity for further examinations. The aim of this randomized, single-blinded, placebo-controlled study was to do a systematic examination of the effects of different antidopaminergic mechanisms on prolactin secretion in healthy volunteers. A 7-day intervention was performed with aripiprazole, haloperidol, or reserpine. Prolactin levels changed significantly in the haloperidol (from 177.2 ± 74.6 to 350.7 ± 202.6 mU/L; P < 0.0001) and in the reserpine groups (from 149.6 ± 80.2 to 540.3 ± 280.8 mU/L; P < 0.0001) but not after aripiprazole (from 160.9 ± 65.0 to 189.6 ± 209.6 mU/L; P = 0.69) or placebo (from 211.6 ± 113.4 mU/L to 196.1 ± 85.6 mU/L; P = 0.8). After haloperidol and reserpine, increases in prolactin were significantly more pronounced in women than in men. Furthermore, in women using hormonal contraception, the increase in prolactin was significantly greater than in those without additional estrogen supply. These results demonstrate that the effect of antipsychotic drugs on prolactin levels strongly depends on their mechanism of action. Reserpine, a vesicular monoamine transporter type 2 blocker, causes the most distinct increase. This implies that D₂ receptor blockade on the lactotrophs is not the sole major cause leading to hyperprolactinemia. The partial agonistic effect of aripiprazole was sufficient to maintain prolactin on physiologic levels. The strong influences of sex and hormonal contraception underline the sensitizing effect of estrogens to the antipsychotic-induced prolactin increase.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University and JARA-Translational Brain Medicine, Aachen, Germany. tveselinovic@ukaachen.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Veselinović
authors.forename: Holger
authors.initials: H
authors.lastname: Schorn
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Vernaleken
authors.forename: Katharina
authors.initials: K
authors.lastname: Schiffl
authors.forename: Majken
authors.initials: M
authors.lastname: Klomp
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D000068180:Aripiprazole; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology*; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; D011388:Prolactin; D006220:Haloperidol; D018967:Risperidone; D004298:Dopamine