Efficacy and safety of dopamine agonists in patients treated with antipsychotics and presenting a macroprolactinoma

in European Journal of Endocrinology

Correspondence should be addressed to P Chanson; Email: philippe.chanson@bct.aphp.fr
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Context

In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge.

Objective

Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics.

Design

This was a multicenter (France and Belgium) retrospective study.

Patients

Eighteen patients treated with antipsychotics were included.

Results

Under DA, median PRL levels decreased from 1247 (117–81 132) to 42 (4–573) ng/mL (P = 0.008), from 3850 (449–38 000) to 141 (60–6000) ng/mL (P = 0.037) and from 1664 (94–9400) to 1215 (48–5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0–57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions.

Conclusion

Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.

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  • 1

    ChansonPMaiterD. The epidemiology, diagnosis and treatment of prolactinomas: the old and the new. Best Practice and Research: Clinical Endocrinology and Metabolism 2019 33 101290. (https://doi.org/10.1016/j.beem.2019.101290)

    • Search Google Scholar
    • Export Citation
  • 2

    JongsmaHETurnerCKirkbrideJBJonesPB. International incidence of psychotic disorders, 2002–17: a systematic review and meta-analysis. Lancet Public Health 2019 4 e229e244. (https://doi.org/10.1016/S2468-2667(19)30056-8)

    • Search Google Scholar
    • Export Citation
  • 3

    Moreno-KustnerBMartinCPastorL. Prevalence of psychotic disorders and its association with methodological issues. A systematic review and meta-analyses. PLoS One 2018 13 e0195687. (https://doi.org/10.1371/journal.pone.0195687)

    • Search Google Scholar
    • Export Citation
  • 4

    LiebermanJAFirstMB. Psychotic disorders. New England Journal of Medicine 2018 379 270280. (https://doi.org/10.1056/NEJMra1801490)

  • 5

    MiyamotoSMiyakeNJarskogLFFleischhackerWWLiebermanJA. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Molecular Psychiatry 2012 17 12061227. (https://doi.org/10.1038/mp.2012.47)

    • Search Google Scholar
    • Export Citation
  • 6

    MolitchME. Drugs and prolactin. Pituitary 2008 11 209218. (https://doi.org/10.1007/s11102-008-0106-6)

  • 7

    TurronePKapurSSeemanMVFlintAJ. Elevation of prolactin levels by atypical antipsychotics. American Journal of Psychiatry 2002 159 133135. (https://doi.org/10.1176/appi.ajp.159.1.133)

    • Search Google Scholar
    • Export Citation
  • 8

    HoltRIPevelerRC. Antipsychotics and hyperprolactinaemia: mechanisms, consequences and management. Clinical Endocrinology 2011 74 141147. (https://doi.org/10.1111/j.1365-2265.2010.03814.x)

    • Search Google Scholar
    • Export Citation
  • 9

    LiebermanJAStroupTSMcEvoyJPSwartzMSRosenheckRAPerkinsDOKeefeRSDavisSMDavisCELebowitzBD Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 2005 353 12091223. (https://doi.org/10.1056/NEJMoa051688)

    • Search Google Scholar
    • Export Citation
  • 10

    MelkerssonKHultingAL. Prolactin-secreting pituitary adenoma in neuroleptic treated patients with psychotic disorder. European Archives of Psychiatry and Clinical Neuroscience 2000 250 610. (https://doi.org/10.1007/pl00007539)

    • Search Google Scholar
    • Export Citation
  • 11

    BroekhofRGosselinkMJPijlHGiltayEJ. The effect of aripiprazole and quinagolide, a dopamine agonist, in a patient with symptomatic pituitary prolactinoma and chronic psychosis. General Hospital Psychiatry 2012 34 209.e1209.e3. (https://doi.org/10.1016/j.genhosppsych.2011.07.004)

    • Search Google Scholar
    • Export Citation
  • 12

    PalJKSarinoWA. Effect of risperidone on prolactinoma growth in a psychotic woman. Psychosomatic Medicine 2000 62 736738. (https://doi.org/10.1097/00006842-200009000-00018)

    • Search Google Scholar
    • Export Citation
  • 13

    WeingartenJCThompsonTL 2nd. The effect of thioridazine on prolactinoma growth in a schizophrenic man: case report. General Hospital Psychiatry 1985 7 364366. (https://doi.org/10.1016/0163-8343(85)90053-2)

    • Search Google Scholar
    • Export Citation
  • 14

    PaepegaeyACSalenaveSKamenickyPMaioneLBrailly-TabardSYoungJChansonP. Cabergoline tapering is almost always successful in patients with macroprolactinomas. Journal of the Endocrine Society 2017 1 221230. (https://doi.org/10.1210/js.2017-00038)

    • Search Google Scholar
    • Export Citation
  • 15

    GillamMPMolitchMELombardiGColaoA. Advances in the treatment of prolactinomas. Endocrine Reviews 2006 27 485534. (https://doi.org/10.1210/er.2005-9998)

    • Search Google Scholar
    • Export Citation
  • 16

    ChansonPMaiterD. Prolactinoma. In The Pituitary 4th ed pp 467514. Ed Melmed.S London, UK: Elsevier, 2017.

  • 17

    ColaoADi SarnoALandiMLScavuzzoFCappabiancaPPivonelloRVolpeRDi SalleFCirilloSAnnunziatoL Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. Journal of Clinical Endocrinology and Metabolism 2000 85 22472252. (https://doi.org/10.1210/jcem.85.6.6657)

    • Search Google Scholar
    • Export Citation
  • 18

    DelgrangeEDaemsTVerhelstJAbsRMaiterD. Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients. European Journal of Endocrinology 2009 160 747752. (https://doi.org/10.1530/EJE-09-0012)

    • Search Google Scholar
    • Export Citation
  • 19

    AliSMillerKKFreudenreichO. Management of psychosis associated with a prolactinoma: case report and review of the literature. Psychosomatics 2010 51 370376. (https://doi.org/10.1176/appi.psy.51.5.370)

    • Search Google Scholar
    • Export Citation
  • 20

    Santos AndradeEHPanPMda SilvaPFGadelhaA. New insights in the management of antipsychotics in the treatment of schizophrenia in a patient with prolactinoma: a case report and review of the literature. Case Reports in Medicine 2010 2010 573252. (https://doi.org/10.1155/2010/573252)

    • Search Google Scholar
    • Export Citation
  • 21

    BilalLChingC. Cabergoline-induced psychosis in a patient with undiagnosed depression. Journal of Neuropsychiatry and Clinical Neurosciences 2012 24 E54. (https://doi.org/10.1176/appi.neuropsych.11110348)

    • Search Google Scholar
    • Export Citation
  • 22

    BurbackL. Management of a microprolactinoma with aripiprazole in a woman with cabergoline-induced mania. Endocrinology Diabetes and Metabolism Case Reports 2015 2015 150100. (https://doi.org/10.1530/EDM-15-0100)

    • Search Google Scholar
    • Export Citation
  • 23

    FryePEPariserSFKimMHO’ShaughnessyRW. Bromocriptine associated with symptom exacerbation during neuroleptic treatment of schizoaffective schizophrenia. Journal of Clinical Psychiatry 1982 43 252253.

    • Search Google Scholar
    • Export Citation
  • 24

    MohapatraSNayakMR. Cabergoline-induced mania in a patient of pituitary microadenoma. Indian Journal of Psychological Medicine 2017 39 350351. (https://doi.org/10.4103/0253-7176.207314)

    • Search Google Scholar
    • Export Citation
  • 25

    NiemanDHSutterlandALOttenJBeckerHEDrentMLvan der GaagMBirchwoodMde HaanL. Treating prolactinoma and psychosis: medication and cognitive behavioural therapy. BMJ Case Reports 2011 2011. (https://doi.org/10.1136/bcr.07.2010.3185)

    • Search Google Scholar
    • Export Citation
  • 26

    PeterSAAutzAJean-SimonML. Bromocriptine-induced schizophrenia. Journal of the National Medical Association 1993 85 700701.

  • 27

    VerhelstJAbsRMaiterDvan den BruelAVandewegheMVelkeniersBMockelJLamberigtsGPetrossiansPCoremansP Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. Journal of Clinical Endocrinology and Metabolism 1999 84 25182522. (https://doi.org/10.1210/jcem.84.7.5810)

    • Search Google Scholar
    • Export Citation
  • 28

    KalkavouraCSMichopoulosIArvanitakisPTheodoropoulouPDimopoulouKTzebelikosELykourasL. Effects of cabergoline on hyperprolactinemia, psychopathology, and sexual functioning in schizophrenic patients. Experimental and Clinical Psychopharmacology 2013 21 332341. (https://doi.org/10.1037/a0033448)

    • Search Google Scholar
    • Export Citation
  • 29

    CavallaroRCocchiFAngeloneSMLattuadaESmeraldiE. Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study. Journal of Clinical Psychiatry 2004 65 187190. (https://doi.org/10.4088/jcp.v65n0207)

    • Search Google Scholar
    • Export Citation
  • 30

    CohnJBBrustJDiSerioFSingerJ. Effect of bromocriptine mesylate on induced hyperprolactinemia in stabilized psychiatric outpatients undergoing neuroleptic treatment. Neuropsychobiology 1985 13 173179. (https://doi.org/10.1159/000118184)

    • Search Google Scholar
    • Export Citation
  • 31

    PollockAMcLarenEH. Serum prolactin concentration in patients taking neuroleptic drugs. Clinical Endocrinology 1998 49 513516. (https://doi.org/10.1046/j.1365-2265.1998.00569.x)

    • Search Google Scholar
    • Export Citation
  • 32

    TollinSR. Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinemia in patients with psychotic disorders. Journal of Endocrinological Investigation 2000 23 765770. (https://doi.org/10.1007/BF03345068)

    • Search Google Scholar
    • Export Citation
  • 33

    ChangSCChenCHLuML. Cabergoline-induced psychotic exacerbation in schizophrenic patients. General Hospital Psychiatry 2008 30 378380. (https://doi.org/10.1016/j.genhosppsych.2007.11.002)

    • Search Google Scholar
    • Export Citation
  • 34

    SmithS. Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine? Journal of Reproductive Medicine 1992 37 737740.

    • Search Google Scholar
    • Export Citation
  • 35

    HofferZSRothRLMathewsM. Evidence for the partial dopamine-receptor agonist aripiprazole as a first-line treatment of psychosis in patients with iatrogenic or tumorogenic hyperprolactinemia. Psychosomatics 2009 50 317324. (https://doi.org/10.1176/appi.psy.50.4.317)

    • Search Google Scholar
    • Export Citation
  • 36

    IoachimescuAGFleseriuMHoffmanARVaughanIII TBKatznelsonL. Psychological effects of dopamine agonist treatment in patients with hyperprolactinemia and prolactin-secreting adenomas. European Journal of Endocrinology 2019 180 3140. (https://doi.org/10.1530/EJE-18-0682)

    • Search Google Scholar
    • Export Citation
  • 37

    DogansenSCCikrikciliUOrukGKutbayNOTanrikuluSHekimsoyZHadzalicAGorarSOmmaTMertM Dopamine agonist-induced impulse control disorders in patients with prolactinoma: a cross-sectional multicenter study. Journal of Clinical Endocrinology and Metabolism 2019 104 25272534. (https://doi.org/10.1210/jc.2018-02202)

    • Search Google Scholar
    • Export Citation
  • 38

    WebsterJ. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Safety 1996 14 228238. (https://doi.org/10.2165/00002018-199614040-00003)

    • Search Google Scholar
    • Export Citation