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Hyperprolactinémies induites par les antipsychotiques : physiopathologie, clinique et surveillance

Antipsychotic-drug-induced hyperprolactinemia: Physiopathology, clinical features and guidance

Doi : 10.1016/j.encep.2012.03.002 

I. Besnard a, V. Auclair a  , G. Callery b, C. Gabriel-Bordenave a, C. Roberge a

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Résumé

L’hyperprolactinémie est un effet secondaire fréquent chez les patients traités par des antipsychotiques. Tous n’ont cependant pas le même potentiel hyperprolactinémiant. La fréquence des signes cliniques est le plus souvent corrélée à l’élévation de la prolactinémie mais l’hyperprolactinémie est parfois asymptomatique. Les manifestations cliniques relèvent principalement de troubles sexuels, de troubles du cycle menstruel et de galactorrhée, en plus d’effets à long terme. Ces signes ne sont pas toujours évoqués par les patients ce qui aboutit à une sous-estimation de la prévalence des hyperprolactinémies. Une revue de la littérature nous permet de proposer un bilan préthérapeutique. Le suivi en cours de traitement a, quant à lui, fait l’objet de recommandations par un groupe international d’experts en psychiatrie, médecine, toxicologie et pharmacologie qui conseille à la fois une surveillance clinique et biologique. Une conduite à tenir en cas d’hyperprolactinémie chez un patient sous antipsychotique est également décrite.

Summary

Background

Hyperprolactinemia is a frequent but neglected adverse effect observed in patients treated with antipsychotic-drugs. In this review, we summarize its physiopathogenetic mechanism, its clinical manifestations in men and women, and the way to manage it.

Literature findings

Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary. Its synthesis and release are under the control of peptides, steroids and neurotransmitters. The main inhibitory regulation is made by dopamine, which binds dopamine receptors D2 on the membrane of lactotroph cells. Antipsychotic-drugs block these receptors and thus remove the inhibitory effect of dopamine on prolactin secretion. All antipsychotic-drugs block D2 receptors and all can induce hyperprolactinemia. Nonetheless, it seems that the faster the antipsychotic-drug dissociates from D2 receptors, the lesser the increase of prolactin in the plasma. Another way to explain hyperprolactinemia is the ability of antipsychotic-drugs to cross the blood-brain barrier. The role of their metabolites should also be considered. For these reasons, one can distinguish prolactin-raising (conventional neuroleptics, amisulpride, risperidone) and prolactin-sparing (clozapine, aripiprazole, olanzapine) antipsychotics. An English study showed that 18% of men and 47% of women treated with antipsychotics for severe mental illness had a prolactin level above the normal range. Hyperprolactinemia is in fact more frequent in women than in men. Sometimes it is asymptomatic, but the higher the prolactin level is, the more patients have clinical manifestations. Some symptoms are due to the hypogonadism caused by prolactin, which disturbs hypothalamic-pituitary axis function, and others are due to direct effects on target tissues. Consequently, patients can suffer from sexual dysfunction, infertility, amenorrhea, gynecomastia or galactorrhoea. Data suggest that these symptoms are common, but patients don’t mention them spontaneously and clinicians underestimate their prevalence. In the long-term, hypogonadism involves a premature bone loss in men and women. Klibanski and colleagues showed that this loss is significant only in women with hyperprolactinemia associated with amenorrhea. That suggests that prolactin is not directly responsible for this clinical feature. Nevertheless, prolactin seems to be involved in the development of breast cancer, but its role is unclear for prostate cancer.

Discussion

Our review promotes a check-up before beginning a treatment with antipsychotic agents. First, a baseline prolactin level should be measured. It should also include the research on previous treatment with antipsychotic-drugs and the assessment of adverse effects suggestive of hyperprolactinemia. Questioning should finally look for any contra-indication to antipsychotics. Monitoring during antipsychotic treatment has been studied by a group of international experts in psychiatry, medicine, toxicology and pharmacy who made a critical review of clinical guidance on hyperprolactinemia. Experts notify that it is important to check whether patients have any sexual dysfunction, such as loss of libido or menstrual irregularity, and galactorrhoea. Prolactin level should also be controlled after three months of stable dose treatment, or if any clinical feature of hyperprolactinemia appears. If a patient prescribed antipsychotic-drugs has a confirmed prolactin level above the normal range, it is necessary to exclude other causes of hyperprolactinemia. If antipsychotics are really involved, the management should be adapted with the prolactin level and the patient him/herself. To summarize, clinicians can decrease the dose of the antipsychotic or switch to a prolactin-sparing drug. Oral contraceptives can be added whether to prevent pregnancy or to prevent bone loss and osteoporosis. Finally, experts recommend reserving dopamine agonists to treat antipsychotic-induced hyperprolactinemia in very exceptional circumstances as it can worsen the mental illness.


Mots clés : Prolactine, Hyperprolactinémie, Neuroleptiques, Conduite à tenir

Keywords : Prolactin, Hyperprolactinemia, Antipsychotic agents, Guidelines


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© 2013  Publié par Elsevier Masson SAS.
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