Prolactin awareness: An essential consideration for physical health in schizophrenia

https://doi.org/10.1016/j.euroneuro.2008.02.004Get rights and content

Abstract

Elevations in serum prolactin levels (hyperprolactinaemia) are a common side effect of conventional and some atypical antipsychotic treatments. In patients with schizophrenia, the adverse effects of antipsychotic-induced hyperprolactinaemia on physical health (e.g. fertility problems, sexual dysfunction and reduced bone mineral density) are gaining attention. Accumulating evidence shows consistent ‘prolactin-raising’ effects of conventional antipsychotics and risperidone compared with other current atypical antipsychotics, which are more likely to have ‘prolactin-sparing’ properties. Prolactin-sparing antipsychotics (for example, aripiprazole and quetiapine) tend to show lower frequencies of hyperprolactinaemia-associated side effects. In recent studies, aripiprazole-treated patients have demonstrated lower prolactin levels compared with patients receiving other prolactin-sparing antipsychotics. There is a lack of robust recommendations for monitoring prolactin elevation among patients receiving antipsychotics. Decreasing the antipsychotic dose or switching to a prolactin-sparing medication are possible management options for antipsychotic-induced hyperprolactinaemia. There is a need to increase awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia.

Introduction

Physical health is frequently impaired in patients with schizophrenia. As well as lifestyle, the adverse effects of antipsychotic treatment are implicated in the increased risk of co-existing physical health problems, such as metabolic syndrome, diabetes and cardiovascular (CV) disease (Newcomer, 2005). Until recently, increased prolactin levels (hyperprolactinaemia), a common side effect of conventional and some atypical antipsychotic treatments, received little attention and was rarely monitored. Hyperprolactinaemia has been shown to adversely influence fertility, sexual function and bone mineral density (Meaney et al., 2004). There is growing awareness of the detrimental effects of elevated prolactin on physical health in patients with schizophrenia treated with antipsychotics.

This paper reviews existing and emerging evidence on antipsychotic-induced hyperprolactinaemia and explores the relationship between antipsychotic effects on prolactin levels and physical health problems in patients with schizophrenia. Current monitoring and management options for antipsychotic-induced hyperprolactinaemia are also reviewed.

Section snippets

Underlying causes of hyperprolactinaemia

Prolactin, a hormone secreted by the anterior pituitary gland, is primarily regulated by dopamine. Levels of prolactin rise during pregnancy and after childbirth to promote the production of milk. However, elevated prolactin levels can be attributed to non-physiological as well as physiological factors (Verhelst and Abs, 2003) (Table 1).

Antipsychotic-induced hyperprolactinaemia in schizophrenia

Antipsychotic treatment effects on serum prolactin levels are well acknowledged (Haddad and Wieck, 2004), and are generally considered to be the cause of increased serum prolactin concentrations in patients with schizophrenia. Several studies have shown that prolactin levels are not elevated in patients who are not receiving antipsychotic treatment (Haddad and Wieck, 2004). Moreover, there is evidence to suggest that unmedicated women with schizophrenia have lower mean daily prolactin levels

Prolactin-sparing vs. prolactin-raising antipsychotic treatment effects

Antipsychotic treatments differ in the extent to which they affect serum prolactin levels (Table 3). There is general agreement that conventional antipsychotics and some atypical antipsychotics (risperidone and amisulpride) elevate prolactin levels (‘prolactin-raising’), whereas the atypical antipsychotics, aripiprazole, clozapine, olanzapine, quetiapine and ziprasidone are less likely to increase prolactin levels (‘prolactin-sparing’) (Chrzanowski et al., 2006, Perlis et al., 2006a, Staller,

Monitoring and management of antipsychotic-induced hyperprolactinaemia

Screening for hyperprolactinaemia is not currently undertaken routinely (Bushe and Shaw, 2007, Maguire, 2002). Moreover, in the case of sexual side effects, professionals may be uncomfortable or under-rate this aspect of their patients’ health. It has been demonstrated that the prevalence of sexual dysfunction is higher when rated by patients than when rated by their psychiatrists (Cutler, 2003). Despite the established evidence of antipsychotic-induced hyperprolactinaemia, published guidance

Conclusion

Antipsychotic-induced hyperprolactinaemia is evident among patients with schizophrenia, and research suggests that elevations in prolactin levels may account for specific physical health problems that are frequently observed in these patients. Conventional antipsychotics and risperidone are consistently associated with ‘prolactin-raising’ effects, whereas other current atypical antipsychotics are more likely to have ‘prolactin-sparing’ properties. Studies have shown that aripiprazole has a

Role of funding source

This supplement was supported by Bristol-Myers Squibb. Editorial support for the preparation of this manuscript was provided by Ogilvy Healthworld Medical Education; funding was provided by Bristol-Myers Squibb. The authors retained full editorial control and responsibilities throughout the preparation of the manuscripts.

Conflict of interest

Dr Montejo has been a speaker for Lilly, AstraZeneca, Bristol-Myers Squibb, Servier, Glaxo-SmithKline, Lundbeck, Sanofi Synthelabo and Wyeth. He is an advisor for Lilly and AstraZeneca and he had received grants from Astra Zeneca, Bristol-Myers Squibb, Lilly, Servier, Glaxo-SmithKline, Lundbeck, Sanofi Synthelabo and Pfizer.

References (55)

  • RaoM.L. et al.

    Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia

    Biol. Psychiatry

    (1994)
  • SunB. et al.

    Physiological roles of prolactin-releasing peptide

    Regul. Pept.

    (2005)
  • AnghelescuI. et al.

    Successful switch to aripiprazole after induction of hyperprolactinemia by ziprasidone: a case report

    J. Clin. Psychiatry

    (2004)
  • BreierA.F. et al.

    Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response

    Am. J. Psychiatry

    (1999)
  • BurrisK.D. et al.

    Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors

    J. Pharmacol. Exp. Ther.

    (2002)
  • BusheC. et al.

    Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics

    J. Psychopharmacol.

    (2007)
  • CaseyD.E. et al.

    Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study

    Psychopharmacology (Berl)

    (2003)
  • ChrzanowskiW.K. et al.

    Effectiveness of long-term aripiprazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine

    Psychopharmacology (Berl)

    (2006)
  • ClevengerC.V. et al.

    Prolactin receptor signal transduction in cells of the immune system

    J. Endocrinol.

    (1998)
  • ComptonM.T. et al.

    Antipsychotic-induced hyperprolactinemia and sexual dysfunction

    Psychopharmacol. Bull.

    (2002)
  • De HertM. et al.

    A case series: evaluation of the metabolic safety of aripiprazole

    Schizophr. Bull.

    (2007)
  • DorevitchA. et al.

    Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior

    Am. J. Psychiatry

    (1999)
  • DuggalH.S. et al.

    High-dose aripiprazole in treatment-resistant schizophrenia

    J. Clin. Psychiatry

    (2006)
  • GhadirianA.M. et al.

    Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients

    J. Nerv. Ment. Dis.

    (1982)
  • GoffinV. et al.

    Prolactin and growth hormone receptors.

    Clin. Endocrinol. (Oxf).

    (1996)
  • HaddadP.M. et al.

    Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management

    Drugs

    (2004)
  • HowardL. et al.

    Risk of hip fracture in patients with a history of schizophrenia

    Br. J. Psychiatry

    (2007)

    • Cited by (69)

    • c-Fos expression response to olanzapine, amisulpride, aripiprazole, and quetiapine single administration in the rat forebrain: Effect of a mild stress preconditioning

      2019, Neurochemistry International
      Citation Excerpt :

      All four antipsychotics have characteristics of atypical group, whereas OLA, ARI, and QUE are neuroleptics with low potency for the extrapyramidal side effects (EPS) (Nemeroff et al., 2002; Natesan et al., 2006). Although AMI induces EPS and hyperprolactinaemia (Montejo, 2008), its effect on the negative and depressive syndromes classifies it as an atypical neuroleptic (Pani and Gessa, 2002; Mandal et al., 2014). Antipsychotic drugs produce different, but characteristic patterns of immediate early gene (c-Fos) expression in rat brain.

    • Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics

      2017, Frontiers in Neuroendocrinology
      Citation Excerpt :

      It should be noted that while prolactin levels tend to normalize a few days after stopping the causal treatment of hyperprolactinemia, in cases of prolonged exposure, the normalization of prolactin levels can be delayed for weeks or even months in the case of longer duration APS (Haddad and Wieck, 2004). Prolactin levels tend to normalize some days after antipsychotic discontinuation (Montejo, 2008). However, with long-acting injectable APS prolactin levels could remain elevated for several months after discontinuation of APS treatment; unfortunately, there is lack of specific information on this regard which it is especially important with risperidone and paliperidone.

    • Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia

      2016, Revista de Psiquiatria y Salud Mental

    • The effect of antipsychotic medication and the associated hyperprolactinemia as a risk factor for periodontal diseases in schizophrenic patients: a cohort retrospective study

      2023, BMC Oral Health

    • Effects of Antipsychotics on Bone Mineral Density in Schizophrenia

      2023, Experimental and Applied Biomedical Research (EABR)

    • Antipsychotic drug—aripiprazole against schizophrenia, its therapeutic and metabolic effects associated with gene polymorphisms

      2023, Pharmacological Reports
    View all citing articles on Scopus
    View full text
    Copyright © 2008 Elsevier B.V. and ECNP. All rights reserved.