A review of the association between antipsychotic use and hyperprolactinaemia

Abstract

Recent evidence linking hyperprolactinaemia to longer-term clinical sequelae, including osteoporosis, hip fractures and possibly breast cancer, is increasing clinical awareness of the relevance of hyperprolactinaemia. A review of the literature finds clinical trials reporting some degree of comparative prolactin data among antipsychotics. Many of the randomised clinical trials (RCTs) do not report categorical rates of hyperprolactinaemia in contrast with the naturalistic studies, making it complex for clinicians to evaluate the extent and severity of hyperprolactinaemia. Hyperprolactinaemia is one of the commonest adverse events reported in clinical trials and can be found in association with all antipsychotics. The highest rates of hyperprolactinaemia are reported in association with risperidone and amisulpride, often as high as 80-90% of all female subjects and consistently greater than with the typical antipsychotics. Significant rates of hyperprolactinaemia of lesser severity and more transience have also been reported in association with other atypical antipsychotics.

ITI-007 demonstrates brain occupancy at serotonin 5-HT2A and dopamine D2 receptors and serotonin transporters using positron emission tomography in healthy volunteers

“…Olanzapine also shows little separation between 5-HT 2A RO (68-78 %) and striatal D 2 RO (85-93 %; Kessler et al 2005). These atypical antipsychotic drugs with relatively high striatial D 2 RO elevate prolactin levels (Bushe et al 2008) and can induce extrapyramidal motor side effects (extrapyramidal symptoms (EPS)) at therapeutic doses (Rummel-Kluge et al 2012). Importantly, selective 5-HT 2A receptor antagonism has been shown to enhance D 2 -receptor-antagonist-mediated antipsychotic efficacy while reducing motor side effects and hyperprolactinemia in animal models (Gardell et al 2007; Wadenberg et al 1996).…”

Prolactin and Schizophrenia, an Evolving Relationship

“…When evaluating hyperprolactinaemia it is also critical to understand the incidence or prevalence of hyperprolactinaemia from the patient perspective as opposed to a mean level from a cohort. Recent data are now tending to more commonly include both variables (Mackin et al, 2011) whereas in our 2008 review of this topic we reported that though 60% of studies reporting prolactin data included some degree of categorical analysis, this was seen mainly in the naturalistic studies (88%) rather than the randomised controlled trials (42%) (Bushe et al, 2008). …”

“…Conversion rates from ng/ml to mIU/L are not standardised and vary between 21.2 and 36 dependent on the assay employed (Bushe et al, 2008). Furthermore, clinical reports do not always report either the normal range utilised or sometimes the units of measurement (McEvoy et al, 2007).…”

“…Data on longer term prolactin levels tend not to report the associated changes in sex hormones making interpretation complex. The topic has, however, been reviewed (Bushe et al, 2008) and in cross-sectional prevalence studies that report bone mineral density loss in association with typicals or risperidone over 8-21 years, the mean cohort values ranged 908-3024 mIU/L . These levels are common and are reached quickly in patients treated with risperidone and amisulpride (Bushe and Shaw 2007; Bushe et al, 2008).…”

Paliperidone-Related Gynecomastia and Treatment: a Case Report

“…Antipsychotic related hyperprolactionemia incidences have been reported to range from 42 to 93% for women and 18 to 72% for men (6). The paliperidone, active metabolites of risperidon and amisulpride, and risperidon's itself are known to cause hyperprolactinemia (7).…”