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Cited by 350Schizophrenia research and treatmentPituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth Factors

The Effects of Novel and Newly Approved Antipsychotics on Serum Prolactin Levels: A Comprehensive Review

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Peuskens, J., Pani, L., Detraux, J., De Hert, M.·2014·CNS Drugs
DOI 10.1007/s40263-014-0157-3PMC PMC4022988
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Abstract

Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966-December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL profiles of antipsychotics in children and adolescents seem to be the same as in adults. The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and probably other neurotransmitter mechanisms) and their blood-brain barrier penetrating capability. Even though antipsychotics are the most common cause of pharmacologically induced HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state.

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  1. [1]Veldhuis JD Johnson ML Operating characteristics of the hypothalamo-pituitary-gonadal axis in men: circadian, ultradian, and pulsatile release of prolactin and its temporal coupling with luteinizing hormone J Clin Endocrinol Metab 1988 67 1 116 123 3379128
  2. [2]Llovera M Touraine P Kelly PA Involvement of prolactin in breast cancer: redefining the molecular targets Exp Gerontol 2000 35 1 41 51 10705038
  3. [3]Nicol M Willis C Yiangou C Relationship between serum prolactin levels and histology of benign and malignant breast lesions: a detailed study of 153 consecutive cases Breast J 2002 8 5 281 285 12199755
  4. [4]Fitzgerald P Dinan TG Prolactin and dopamine: what is the connection? A review article J Psychopharmacol 2008 22 2 Suppl 12 19 18477617
  5. [5]Bushe CJ Bradley A Pendlebury J A review of hyperprolactinaemia and severe mental illness: are there implications for clinical biochemistry? Ann Clin Biochem 2010 47 Pt 4 292 300 20592331
  6. [6]Cookson J Hodgson R Wildgust HJ Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis J Psychopharmacol 2012 26 5 Suppl 42 51 22472310
  7. [7]Jacobson EM Hugo ER Borcherding DC Prolactin in breast and prostate cancer: molecular and genetic perspectives Discov Med 2011 11 59 315 324 21524385
  8. [8]Bernichtein S Touraine P Goffin V New concepts in prolactin biology J Endocrinol 2010 206 1 1 11 20371569
  9. [9]Graham SM Howgate D Anderson W Risk of osteoporosis and fracture incidence in patients on antipsychotic medication Expert Opin Drug Saf 2011 10 4 575 602 21385106
  10. [10]Hankinson SE Willett WC Michaud DS Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women J Natl Cancer Inst 1999 91 7 629 634 10203283
  11. [11]Hamner M The effects of atypical antipsychotics on serum prolactin levels Ann Clin Psychiatry 2002 14 3 163 173 12585566
  12. [12]Meaney AM O’Keane V Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia Life Sci 2002 71 9 979 992 12088758
  13. [13]Hummer M Huber J Hyperprolactinaemia and antipsychotic therapy in schizophrenia Curr Med Res Opin 2004 20 2 189 197 15006013
  14. [14]Goffin V Touraine P Culler MD Drug Insight: prolactin-receptor antagonists, a novel approach to treatment of unresolved systemic and local hyperprolactinemia? Nat Clin Pract Endocrinol Metab 2006 2 10 571 581 17024156
  15. [15]Petty RG Prolactin and antipsychotic medications: mechanism of action Schizophr Res 1999 35 Suppl S67 S73 10190227
  16. [17]La Torre D Falorni A Pharmacological causes of hyperprolactinemia Ther Clin Risk Manag 2007 3 5 929 951 18473017 PMC2376090
  17. [18]Voicu V Medvedovici A Ranetti AE Drug-induced hypo- and hyperprolactinemia: mechanisms, clinical and therapeutic consequences Expert Opin Drug Metab Toxicol 2013 9 8 955 968 23600946
  18. [19]Freeman ME Kanyicska B Lerant A Prolactin: structure, function, and regulation of secretion Physiol Rev 2000 80 4 1523 1631 11015620
  19. [20]Halbreich U Kinon BJ Gilmore JA Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects Psychoneuroendocrinology 2003 28 Suppl 1 53 67 12504072
  20. [21]Emiliano AB Fudge JL From galactorrhea to osteopenia: rethinking serotonin-prolactin interactions Neuropsychopharmacology 2004 29 5 833 846 14997175
  21. [22]Bergemann N Parzer P Mundt C High bone turnover but normal bone mineral density in women suffering from schizophrenia Psychol Med 2008 38 8 1195 1201 18366816
  22. [24]Radl DB Zárate S Jaita G Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent Neuroendocrinology 2008 88 1 43 52 18259092
  23. [25]Tuomisto J Männistö P Neurotransmitter regulation of anterior pituitary hormones Pharmacol Rev 1985 37 3 249 332 2869509
  24. [26]Young RM Lawford BR Barnes M Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele Br J Psychiatry 2004 185 147 151 15286066
  25. [28]American Psychiatric Association Schizophrenia Am J Psychiatry 1997 154 Suppl. 4 11 25 9090368
  26. [29]Molitch ME Medication-induced hyperprolactinemia Mayo Clin Proc 2005 80 8 1050 1057 16092584
  27. [31]Coccaro EF Kavoussi RJ Oakes M 5-HT2a/2c receptor blockade by amesergide fully attenuates prolactin response to d-fenfluramine challenge in physically healthy human subjects Psychopharmacology (Berl) 1996 126 1 24 30 8853213
  28. [32]Xu Y Jones JE Lauzon DA Anderson JG Balthasar N Heisler LK Zinn AR Lowell BB Elmquist JK A serotonin and melanocortin circuit mediates d-fenfluramine anorexia J Neurosci 2010 30 44 14630 14634 21048120 PMC3466475
  29. [33]Murnane KS Kimmel HL Rice KC The neuropharmacology of prolactin secretion elicited by 3,4-methylenedioxymethamphetamine (“ecstasy”): a concurrent microdialysis and plasma analysis study Horm Behav 2012 61 2 181 190 22197270 PMC3278534
  30. [34]Papageorgiou A Denef C Estradiol induces expression of 5-hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 receptor messenger ribonucleic acid in rat anterior pituitary cell aggregates and allows prolactin release via the 5-HT4 receptor Endocrinology 2007 148 3 1384 1395 17122082
  31. [35]Van de Kar LD Rittenhouse PA Li Q Serotonergic regulation of renin and prolactin secretion Behav Brain Res 1996 73 1–2 203 208 8788503
  32. [36]Balsa JA Sánchez-Franco F Pazos F Direct action of serotonin on prolactin, growth hormone, corticotropin and luteinizing hormone release in cocultures of anterior and posterior pituitary lobes: autocrine and/or paracrine action of vasoactive intestinal peptide Neuroendocrinology 1998 68 5 326 333 9822800
  33. [37]Van de Kar LD Javed A Zhang Y 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells J Neurosci 2001 21 10 3572 3579 11331386 PMC6762485
  34. [38]Breton C Pechoux C Morel G Oxytocin receptor messenger ribonucleic acid: characterization, regulation, and cellular localization in the rat pituitary gland Endocrinology 1995 136 7 2928 2936 7540544
  35. [39]Mogg RJ Samson WK Interactions of dopaminergic and peptidergic factors in the control of prolactin release Endocrinology 1990 126 2 728 735 2298169
  36. [40]Wanke IE Rorstad OP Receptors for vasoactive intestinal peptide in rat anterior pituitary glands: localization of binding to lactotropes Endocrinology 1990 126 4 1981 1988 2156675
  37. [41]Samson WK Bianchi R Mogg RJ Oxytocin mediates the hypothalamic action of vasoactive intestinal peptide to stimulate prolactin secretion Endocrinology 1989 124 2 812 819 2912703
  38. [42]Rittenhouse PA Levy AD Li Q Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of prolactin secretion via 5-HT1c/2 receptors Endocrinology 1993 133 2 661 667 8344205
  39. [43]Bagdy G Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses Behav Brain Res 1996 73 1–2 277 280 8788518
  40. [44]Kiss J Halász B Synaptic connections between serotoninergic axon terminals and tyrosine hydroxylase-immunoreactive neurons in the arcuate nucleus of the rat hypothalamus. A combination of electron microscopic autoradiography and immunocytochemistry Brain Res 1986 364 2 284 294 2868780
  41. [45]Mirkes SJ Bethea CL Oestrogen, progesterone and serotonin converge on GABAergic neurones in the monkey hypothalamus J Neuroendocrinol 2001 13 2 182 192 11168844
  42. [47]Chun T-Y Gregg D Sarkar DK Differential regulation by estrogens of growth and prolactin synthesis in pituitary cells suggests that only a small pool of estrogen receptors is required for growth PNAS 1998 95 5 2325 2330 9482884 PMC19333
  43. [48]Yokoyama Y Kitchens WC Toth B Upregulation of hepatic prolactin receptor gene expression by 17β-estradiol following trauma-hemorrhage J Appl Physiol 2003 95 6 2530 2536 12937033
  44. [49]Veselinović T Schorn H Vernaleken IB Impact of different antidopaminergic mechanisms on the dopaminergic control of prolactin secretion J Clin Psychopharmacol 2011 31 2 214 220 21346608
  45. [50]Messini CI Dafopoulos K Chalvatzas N Effect of ghrelin and thyrotropin-releasing hormone on prolactin secretion in normal women Horm Metab Res 2010 42 3 204 208 19844859
  46. [51]Messini CI Dafopoulos K Chalvatzas N Effect of ghrelin and metoclopramide on prolactin secretion in normal women J Endocrinol Invest 2011 34 4 276 279 20530986
  47. [52]Benso A Calvi E Gramaglia E Olivetti I Tomelini M Ghigo E Broglio F Other than growth hormone neuroendocrine actions of ghrelin Endocr Dev 2013 25 59 68 23652392
  48. [53]Zhang-Wong JH Seeman MV Antipsychotic drugs, menstrual regularity and osteoporosis risk Arch Womens Ment Health 2002 5 3 93 98 12510211
  49. [54]Schlechte JA Clinical practice. Prolactinoma N Engl J Med 2003 349 21 2035 2041 14627789
  50. [55]Citrome L Current guidelines and their recommendations for prolactin monitoring in psychosis J Psychopharmacol 2008 22 2 Suppl 90 97 18477625
  51. [56]Peuskens J, editor. A literature review of “Prolactin in schizophrenia”. Clear perspectives: management issues in schizophrenia, vol. 1, no. 3 (1997).
  52. [57]Montejo AL Prolactin awareness: an essential consideration for physical health in schizophrenia Eur Neuropsychopharmacol 2008 18 Suppl 2 S108 S114 18346598
  53. [58]Brown PJ Cleghorn JM Brown GM Seasonal variations in prolactin levels in schizophrenia Psychiatry Res 1988 25 2 157 162 3174903
  54. [59]Garde AH Hansen AM Skovgaard LT Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women Clin Chem 2000 46 4 551 559 10759480
  55. [60]Tanner MJ Hadlow NC Wardrop R Variation of female prolactin levels with menopausal status and phase of menstrual cycle Aust N Z J Obstet Gynaecol 2011 51 4 321 324 21806583
  56. [61]Rosenbloom AL. Hyperprolactinemia with antipsychotic drugs in children and adolescents. Int J Pediatr Endocrinol. 2010; pii: 159402. PMC2943074 20871665
  57. [62]Chahal J Schlechte J Hyperprolactinemia Pituitary 2008 11 2 141 146 18404389
  58. [63]Mackin P Waton A Nulkar A Prolactin and smoking status in antipsychotic-treated patients J Psychopharmacol 2011 25 5 698 703 20699354
  59. [64]Zhang X Bu R Sha W Serum prolactin and smoking status in chronic antipsychotic-treated male patients with schizophrenia Psychiatry Res 2013 209 2 239 241 23684052
  60. [65]Ohta C Yasui-Furukori N Furukori H The effect of smoking status on the plasma concentration of prolactin already elevated by risperidone treatment in schizophrenia patients Prog Neuropsychopharmacol Biol Psychiatry 2011 35 2 573 576 21216266
  61. [66]Bushe C Shaw M Peveler RC A review of the association between antipsychotic use and hyperprolactinaemia J Psychopharmacol 2008 22 2 Suppl 46 55 18477620
  62. [67]Peveler RC Branford D Citrome L Antipsychotics and hyperprolactinaemia: clinical recommendations J Psychopharmacol 2008 22 2 Suppl 98 103 18477626
  63. [68]Kelly DL Wehring HJ Earl AK Sullivan K Dickerson FB Feldman S McMahon RP Buchanan RW Warfel D Keller WR Fischer BA Shim JC Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic ELevated prolactin) BMC Psychiatry 2013 13 1 214 23968123 PMC3766216
  64. [69]Tsuboi T Bies RR Suzuki T Hyperprolactinemia and estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data Prog Neuropsychopharmacol Biol Psychiatry 2013 45 178 182 23727135
  65. [71]Citrome L Cucchiaro J Sarma K Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month, double-blind, active-controlled study Int Clin Psychopharmacol 2012 27 3 165 176 22395527
  66. [72]Kikuchi T Iwamoto K Sasada K Sexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics Prog Neuropsychopharmacol Biol Psychiatry 2012 37 1 26 32 22172534
  67. [73]Nagai G Mihara K Nakamura A Prolactin concentrations during aripiprazole treatment in relation to sex, plasma drugs concentrations and genetic polymorphisms of dopamine D2 receptor and cytochrome P450 2D6 in Japanese patients with schizophrenia Psychiatry Clin Neurosci 2012 66 6 518 524 23066770
  68. [74]Pérez-Iglesias R Mata I Martínez-García O Long-term effect of haloperidol, olanzapine, and risperidone on plasma prolactin levels in patients with first-episode psychosis J Clin Psychopharmacol 2012 32 6 804 808 23131886
  69. [75]Sugawara N Yasui-Furukori N Fujii A No association between bone mass and prolactin levels among patients with schizophrenia Hum Psychopharmacol 2011 26 8 596 601 22105774
  70. [76]Grootens KP van Veelen NM Peuskens J Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial Schizophr Bull 2011 37 2 352 361 19542525 PMC3044623
  71. [77]Li H Rui Q Ning X A comparative study of paliperidone palmitate and risperidone long-acting injectable therapy in schizophrenia Prog Neuropsychopharmacol Biol Psychiatry 2011 35 4 1002 1008 21315787
  72. [78]Gopal S Vijapurkar U Lim P A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia J Psychopharmacol 2011 25 5 685 697 20615933
  73. [79]Aston J Rechsteiner E Bull N Borgwardt S Gschwandtner U Riecher-Rössler A Hyperprolactinaemia in early psychosis—not only due to antipsychotics Prog Neuropsychopharmacol Biol Psychiatry 2010 34 7 1342 1344 20188136
  74. [80]Arakawa R Okumura M Ito H Positron emission tomography measurement of dopamine D2 receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia J Clin Psychiatry 2010 71 9 1131 1137 20361897
  75. [81]Bushe C Sniadecki J Bradley AJ Comparison of metabolic and prolactin variables from a six-month randomised trial of olanzapine and quetiapine in schizophrenia J Psychopharmacol 2010 24 7 1001 1009 19240085
  76. [82]Citrome L Stauffer VL Chen L Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration J Clin Psychopharmacol 2009 29 3 278 283 19440083
  77. [83]Kwon JS Jang JH Kang DH Long-term efficacy and safety of aripiprazole in patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder: 26-week prospective study Psychiatry Clin Neurosci 2009 63 1 73 81 19154213
  78. [84]Kryzhanovskaya L Schulz SC McDougle C Olanzapine versus placebo in adolescents with schizophrenia: a 6-week, randomized, double-blind, placebo-controlled trial J Am Acad Child Adolesc Psychiatry 2009 48 1 60 70 19057413
  79. [85]Kim SW Shin IS Kim JM Effectiveness of switching to aripiprazole from atypical antipsychotics in patients with schizophrenia Clin Neuropharmacol 2009 32 5 243 249 19620849
  80. [86]Byerly MJ Marcus RN Tran QV Effects of aripiprazole on prolactin levels in subjects with schizophrenia during cross-titration with risperidone or olanzapine: analysis of a randomized, open-label study Schizophr Res 2009 107 2–3 218 222 19038534
  81. [88]Liu-Seifert H Kinon BJ Tennant CJ Sexual dysfunction in patients with schizophrenia treated with conventional antipsychotics or risperidone Neuropsychiatr Dis Treat 2009 5 47 54 19557099 PMC2695222
  82. [90]Tschoner A Engl J Rettenbacher MA Is second-generation antipsychotic-induced hyperprolactinemia due to biologically active prolactin or to biologically inactive macroprolactin? Results from a prospective study J Clin Psychiatry 2009 70 2 293 294 19265646
  83. [91]Meltzer HY Bobo WV Nuamah IF Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week, placebo-controlled studies J Clin Psychiatry 2008 69 5 817 829 18466043
  84. [92]Emsley R Berwaerts J Eerdekens M Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies Int Clin Psychopharmacol 2008 23 6 343 356 18854723
  85. [93]Kahn RS Fleischhacker WW Boter H Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial Lancet 2008 371 9618 1085 1097 18374841
  86. [94]Lu ML Shen WW Chen CH Time course of the changes in antipsychotic-induced hyperprolactinemia following the switch to aripiprazole Prog Neuropsychopharmacol Biol Psychiatry 2008 32 8 1978 1981 18848860
  87. [96]Yuan HN Wang CY Sze CW A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia J Clin Psychopharmacol 2008 28 3 264 370 18480682
  88. [97]Kishimoto T Watanabe K Shimada N Antipsychotic-induced hyperprolactinemia inhibits the hypothalamo-pituitary-gonadal axis and reduces bone mineral density in male patients with schizophrenia J Clin Psychiatry 2008 69 3 385 391 18278991
  89. [98]Howes OD Wheeler MJ Pilowsky LS Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder J Clin Psychiatry 2007 68 3 361 367 17388704 PMC3666283
  90. [99]Kinon BJ Ahl J Liu-Seifert H Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine Psychoneuroendocrinology 2006 31 5 577 588 16488084
  91. [100]Kelly DL Conley RR A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia Psychoneuroendocrinology 2006 31 3 340 346 16198059
  92. [101]Schooler N Rabinowitz J Davidson M Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial Am J Psychiatry 2005 162 5 947 953 15863797
  93. [102]Volavka J Czobor P Cooper TB Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol J Clin Psychiatry 2004 65 1 57 61 14744169
  94. [103]Addington DE Pantelis C Dineen M Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial J Clin Psychiatry 2004 65 12 1624 1633 15641867
  95. [105]Montgomery J Winterbottom E Jessani M Prevalence of hyperprolactinemia in schizophrenia: association with typical and atypical antipsychotic treatment J Clin Psychiatry 2004 65 11 1491 1498 15554761
  96. [106]Cavallaro R Cocchi F Angelone SM Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study J Clin Psychiatry 2004 65 2 187 190 15003071
  97. [107]Kinon BJ Ahl J Liu-Seifert H Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone Psychoneuroendocrinology 2003 28 Suppl 2 55 68 12650681
  98. [108]Potkin SG Saha AR Kujawa MJ Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder Arch Gen Psychiatry 2003 60 7 681 690 12860772
  99. [109]Canuso CM Goldstein JM Wojcik J Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder Psychiatry Res 2002 111 1 11 20 12140115
  100. [110]Aizenberg D Modai I Landa A Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classic antipsychotics versus clozapine J Clin Psychiatry 2001 62 7 541 544 11488365
  101. [111]Huber TJ Rollnik J Wilhelms J Estradiol levels in psychotic disorders Psychoneuroendocrinology 2001 26 1 27 35 11070332
  102. [112]David SR Taylor CC Kinon BJ The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia Clin Ther 2000 22 9 1085 1096 11048906
  103. [113]Peuskens J Link CG A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia Acta Psychiatr Scand 1997 96 4 265 273 9350955
  104. [114]Crawford AM Beasley CM Jr Tollefson GD The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations Schizophr Res 1997 26 1 41 54 9376336
  105. [115]Walters J Jones I Clinical questions and uncertainty—prolactin measurement in patients with schizophrenia and bipolar disorder J Psychopharmacol 2008 22 2 Suppl 82 89 18477624
  106. [116]Ali S Miller KK Freudenreich O Management of psychosis associated with a prolactinoma: case report and review of the literature Psychosomatics 2010 51 5 370 376 20833935 PMC3667992
  107. [117]Alkabbani AG Mon SY Hatipoglu B Kennedy L Faiman C Weil RJ Hamrahian AH Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth? Pituitary 2013 23468127
  108. [118]Bayrak A Saadat P Mor E Chong L Paulson RJ Sokol RZ Pituitary imaging is indicated for the evaluation of hyperprolactinemia Fertil Steril 2005 84 1 181 185 16009175
  109. [120]Arcari GT Mendes AK Sothern RB A risperidone-induced prolactinoma resolved when a woman with schizoaffective disorder switched to ziprasidone: a case report Innov Clin Neurosci 2012 9 9 21 24 23074699 PMC3472901
  110. [121]Broekhof R Gosselink MJ Pijl H The effect of aripiprazole and quinagolide, a dopamine agonist, in a patient with symptomatic pituitary prolactinoma and chronic psychosis Gen Hosp Psychiatry 2012 34 2 209.e1–3 21872335
  111. [122]Szarfman A Tonning JM Levine JG Atypical antipsychotics and pituitary tumors: a pharmacovigilance study Pharmacotherapy 2006 26 6 748 758 16716128
  112. [123]Lee BJ Lee SJ Kim MK Effect of aripiprazole on cognitive function and hyperprolactinemia in patients with schizophrenia treated with risperidone Clin Psychopharmacol Neurosci 2013 11 2 60 66 24023549 PMC3766756
  113. [124]Coppola D Thiagarajah S Qiu H Regarding “A risperidone-induced prolactinoma resolved when a woman with schizoaffective disorder switched to ziprasidone: a case report” Innov Clin Neurosci 2013 10 2 12 16 23556137 PMC3615507
  114. [125]Gianfrancesco FD Pandina G Mahmoud R Potential bias in testing for hyperprolactinemia and pituitary tumors in risperidone-treated patients: a claims-based study Ann Gen Psychiatry 2009 8 5 19210771 PMC2649125
  115. [126]Serri O Chik CL Ur E Diagnosis and management of hyperprolactinemia CMAJ 2003 169 6 575 581 12975226 PMC191295
  116. [127]Kleinberg DL Davis JM De Coster R Prolactin levels and adverse events in patients treated with risperidone J Clin Psychopharmacol 1999 19 1 57 61 9934944
  117. [129]Malik P Kemmler G Hummer M EUFEST Study Group Sexual dysfunction in first-episode schizophrenia patients: results from European First Episode Schizophrenia Trial J Clin Psychopharmacol 2011 31 3 274 280 21508850
  118. [130]Biller BM Diagnostic evaluation of hyperprolactinemia J Reprod Med 1999 44 12 Suppl 1095 1099 10649817
  119. [131]Bushe C Yeomans D Floyd T Categorical prevalence and severity of hyperprolactinaemia in two UK cohorts of patients with severe mental illness during treatment with antipsychotics J Psychopharmacol 2008 22 2 Suppl 56 62 18477621
  120. [132]Yasui-Furukori N Saito M Nakagami T Gender-specific prolactin response to antipsychotic treatments with risperidone and olanzapine and its relationship to drug concentrations in patients with acutely exacerbated schizophrenia Prog Neuropsychopharmacol Biol Psychiatry 2010 34 3 537 540 20170699
  121. [133]Yasui-Furukori N Furukori H Sugawara N Prolactin fluctuation over the course of a day during treatments with three atypical antipsychotics in schizophrenic patients Hum Psychopharmacol 2010 25 3 236 242 20373475
  122. [134]Yasui-Furukori N Saito M Tsuchimine S Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients Prog Neuropsychopharmacol Biol Psychiatry 2008 32 6 1491 1495 18579277
  123. [135]Yasui-Furukori N Tsuchimine S Saito M Association between major Multidrug Resistance 1 (MDR1) gene polymorphisms and plasma concentration of prolactin during risperidone treatment in schizophrenic patients Prog Neuropsychopharmacol Biol Psychiatry 2007 31 6 1230 1234 17559997
  124. [136]Sawamura K Suzuki Y Fukui N Gender differences in prolactin elevation induced by olanzapine in Japanese drug-naïve schizophrenic patients Prog Neuropsychopharmacol Biol Psychiatry 2006 30 8 1511 1514 16824658
  125. [137]Wode-Helgodt B Eneroth P Fyrö B Effect of chlorpromazine treatment on prolactin levels in cerebrospinal fluid and plasma of psychotic patients Acta Psychiatr Scand 1977 56 4 280 293 335789
  126. [138]Kuruvilla A Peedicayil J Srikrishna G A study of serum prolactin levels in schizophrenia: comparison of males and females Clin Exp Pharmacol Physiol 1992 19 9 603 606 1356671
  127. [139]Gründer G Wetzel H Schlösser R Neuroendocrine response to antipsychotics: effects of drug type and gender Biol Psychiatry 1999 45 1 89 97 9894580
  128. [140]Kinon BJ Gilmore JA Liu H Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials Psychoneuroendocrinology 2003 28 Suppl 2 69 82 12650682
  129. [141]Smith S Wheeler MJ Murray R The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis J Clin Psychopharmacol 2002 22 2 109 114 11910254
  130. [142]Lee BH Kim YK The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients Prog Neuropsychopharmacol Biol Psychiatry 2006 30 4 658 662 16466670
  131. [143]Halbreich U Kahn LS Hyperprolactinemia and schizophrenia: mechanisms and clinical aspects J Psychiatr Pract 2003 9 5 344 353 15985953
  132. [144]Wudarsky M Nicolson R Hamburger SD Elevated prolactin in pediatric patients on typical and atypical antipsychotics J Child Adolesc Psychopharmacol 1999 9 4 239 245 10630453
  133. [145]Frazier JA Meyer MC Biederman J Risperidone treatment for juvenile bipolar disorder: a retrospective chart review J Am Acad Child Adolesc Psychiatry 1999 38 8 960 965 10434487
  134. [146]Sallee FR Kurlan R Goetz CG Ziprasidone treatment of children and adolescents with Tourette’s syndrome: a pilot study J Am Acad Child Adolesc Psychiatry 2000 39 3 292 299 10714048
  135. [147]Jordan MP Ziprasidone-associated galactorrhea in a female teenager J Am Acad Child Adolesc Psychiatry 2003 42 1 4 5 12500070
  136. [148]Pappagallo M Silva R The effect of atypical antipsychotic agents on prolactin levels in children and adolescents J Child Adolesc Psychopharmacol 2004 14 3 359 371 15650493
  137. [149]Hellings JA Zarcone JR Valdovinos MG Risperidone-induced prolactin elevation in a prospective study of children, adolescents, and adults with mental retardation and pervasive developmental disorders J Child Adolesc Psychopharmacol 2005 15 6 885 892 16379508
  138. [150]Holzer L Eap CB Risperidone-induced symptomatic hyperprolactinaemia in adolescents J Clin Psychopharmacol 2006 26 2 167 171 16633146
  139. [151]Madhusoodanan S Moise D Risperidone-induced hyperprolactinemia in adolescents: A case series J Clin Psychiatry 2006 67 7 1110 1113 16889455
  140. [152]Handen BL Hardan AY Open-label, prospective trial of olanzapine in adolescents with subaverage intelligence and disruptive behavioral disorders J Am Acad Child Adolesc Psychiatry 2006 45 8 928 935 16865035
  141. [153]Migliardi G Spina E D’Arrigo C Short- and long-term effects on prolactin of risperidone and olanzapine treatments in children and adolescents Prog Neuropsychopharmacol Biol Psychiatry 2009 33 8 1496 1501 19706318
  142. [154]Swadi HS Craig BJ Pirwani NZ A trial of quetiapine compared with risperidone in the treatment of first onset psychosis among 15- to 18-year-old adolescents Int Clin Psychopharmacol 2010 25 1 1 6 19809337
  143. [155]Masi G Liboni F Management of schizophrenia in children and adolescents: focus on pharmacotherapy Drugs 2011 71 2 179 208 21275445
  144. [156]Mancini T Casanueva FF Giustina A Hyperprolactinemia and prolactinomas Endocrinol Metab Clin North Am 2008 37 1 67 99, viii 18226731
  145. [157]Schyve PM Smithline F Meltzer HY Neuroleptic-induced prolactin level elevation and breast cancer: an emerging clinical issue Arch Gen Psychiatry 1978 35 11 1291 1301 30426
  146. [158]Bronstein MD DeGroot LL Jameson LJ Disorders of prolactin secretion and prolactinomas Endocrinology 2006 USA Elsevier Saunders
  147. [159]Madhusoodanan S Parida S Jimenez C Hyperprolactinemia associated with psychotropics—a review Hum Psychopharmacol 2010 25 4 281 297 20521318
  148. [160]Naidoo U Goff DC Klibanski A Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents Psychoneuroendocrinology 2003 28 Suppl 2 97 108 12650684
  149. [161]Segal M Avital A Rojas M Serum prolactin levels in unmedicated first-episode and recurrent schizophrenia patients: a possible marker for the disease’s subtypes Psychiatry Res 2004 127 3 227 235 15296822
  150. [162]Mazure CM Quinlan DM Bowers MB Jr Recent life stressors and biological markers in newly admitted psychotic patients Biol Psychiatry 1997 41 8 865 870 9099413
  151. [164]Keks NA Copolov DL Singh BS Abnormal prolactin response to haloperidol challenge in men with schizophrenia Am J Psychiatry 1987 144 10 1335 1337 3661768
  152. [165]Meltzer HY Sachar EJ Frantz AG Serum prolactin levels in unmedicated schizophrenic patients Arch Gen Psychiatry 1974 31 4 564 569 4422004
  153. [166]Tsigkaropoulou E Peppa M Zompola C Hypogonadism due to hyperprolactinemia and subsequent first episode of psychosis Gend Med 2012 9 1 56 60 22333523
  154. [167]Segal M Avital A Berstein S Prolactin and estradiol serum levels in unmedicated male paranoid schizophrenia patients Prog Neuropsychopharmacol Biol Psychiatry 2007 31 2 378 382 17110010
  155. [168]Garcia-Rizo C Fernandez-Egea E Oliveira C Prolactin concentrations in newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis Schizophr Res 2012 134 1 16 19 21831600 PMC4185192
  156. [169]Riecher-Rössler A Rybakowski JK Pflueger MO Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis Psychol Med 2013 43 12 2571 2582 23590895
  157. [170]Rybakowski JK Dmitrzak-Weglarz M Kapelski P Functional −1149g/t polymorphism of the prolactin gene in schizophrenia Neuropsychobiology 2012 65 1 41 44 22094377
  158. [171]Tandon R Antipsychotics in the treatment of schizophrenia: an overview J Clin Psychiatry 2011 72 Suppl 1 4 8 22217436
  159. [172]Doknic M Maric NP Britvic D Bone remodeling, bone mass and weight gain in patients with stabilized schizophrenia in real-life conditions treated with long-acting injectable risperidone Neuroendocrinology 2011 94 3 246 254 21986470
  160. [173]Melkersson K Berinder K Hulting AL Effect of antipsychotic-induced hyperprolactinemia on anthropometric measures, insulin sensitivity and lipid profile in patients with schizophrenia or related psychoses Neuro Endocrinol Lett 2011 32 4 428 436 21876517
  161. [174]Haefliger T Bonsack C Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone Encephale 2006 32 1 Pt 1 97 105 16633296
  162. [175]Dossenbach M Hodge A Anders M Prevalence of sexual dysfunction in patients with schizophrenia: international variation and underestimation Int J Neuropsychopharmacol 2005 8 2 195 201 15631645
  163. [176]Toren P Ratner S Laor N Benefit-risk assessment of atypical antipsychotics in the treatment of schizophrenia and comorbid disorders in children and adolescents Drug Saf 2004 27 14 1135 1156 15554747
  164. [177]Dickson RA Glazer WM Neuroleptic-induced hyperprolactinemia Schizophr Res 1999 35 Suppl S75 S86 10190228
  165. [178]Eberhard J Lindstrom E Holstad M Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders Acta Psychiatr Scand 2007 115 4 268 276 17355517
  166. [180]Marken PA Haykal RF Fisher JN Management of psychotropic-induced hyperprolactinemia Clin Pharm 1992 11 10 851 856 1341991
  167. [181]Brown WA Laughren TP Tolerance to the prolactin-elevating effect of neuroleptics Psychiatry Res 1981 5 3 317 322 6119716
  168. [182]Meltzer HY Fang VS The effect of neuroleptics on serum prolactin in schizophrenic patients Arch Gen Psychiatry 1976 33 3 279 286 1259521
  169. [183]Meltzer HY Fang VS Sachar EJ Serum prolactin levels in schizophrenia—effect of antipsychotic drugs: a preliminary report Hormones, behaviour, and psychopathology 1976 New York Raven Press 177 190
  170. [184]Igarashi Y Higuchi T Toyoshima R Tolerance to prolactin secretion in the long-term treatment with neuroleptics in schizophrenia Adv Biochem Psychopharmacol 1985 40 95 98 2862770
  171. [185]Meltzer HY Long-term effects of neuroleptic drugs on the neuroendocrine system Adv Biochem Psychopharmacol 1985 40 59 68 2862768
  172. [186]Spitzer M Sajjad R Benjamin F Pattern of development of hyperprolactinemia after initiation of haloperidol therapy Obstet Gynecol 1998 91 5 Pt 1 693 695 9572212
  173. [187]Suzuki Y Sugai T Fukui N Differences in plasma prolactin levels in patients with schizophrenia treated on monotherapy with five second-generation antipsychotics Schizophr Res 2013 145 1–3 116 119 23375624
  174. [188]Meltzer HY Matsubara S Lee JC The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs Psychopharmacol Bull 1989 25 3 390 392 2576319
  175. [189]Hagen C Pedersen PB Jensen SB The effect of sulpiride induced hyperprolactinaemia on glucose tolerance and insulin secretion in normal subjects Clin Endocrinol (Oxf) 1979 10 1 55 60 436305
  176. [190]Juruena MF de Sena EP de Oliveira IR Safety and tolerability of antipsychotics: focus on amisulpride Drug Healthc Patient Saf 2010 2 205 211 21701632 PMC3108712
  177. [191]Lee BH Kang SG Kim TW Hyperprolactinemia induced by low-dosage amisulpride in Korean psychiatric patients Psychiatry Clin Neurosci 2012 66 1 69 73 22250612
  178. [192]Kopecek M Bares M Svarc J Hyperprolactinemia after low dose of amisulpride Neuro Endocrinol Lett 2004 25 6 419 422 15665803
  179. [193]Kopecek M Bares M Horacek J Normalization of hyperprolactinaemia after withdrawal of a low dose of amisulpride Neuro Endocrinol Lett 2005 26 4 320 16136015
  180. [194]Holt RI Peveler RC Antipsychotics and hyperprolactinaemia: mechanisms, consequences and management Clin Endocrinol (Oxf) 2011 74 2 141 147 20455888
  181. [195]Andrade C Low-dose amisulpride and elevation in serum prolactin J Clin Psychiatry 2013 74 6 e558 e560 23842026
  182. [196]Fric M Laux G Prolactin levels and symptoms of hyperprolactinemia in patients treated with amisulpride, risperidone, olanzapine and quetiapine Psychiatr Prax 2003 30 Suppl 2 97 101 13130349
  183. [197]McKeage K Plosker GL Amisulpride: a review of its use in the management of schizophrenia CNS Drugs 2004 18 13 933 956 15521794
  184. [198]Paparrigopoulos T Liappas J Tzavellas E Amisulpride-induced hyperprolactinemia is reversible following discontinuation Prog Neuropsychopharmacol Biol Psychiatry 2007 31 1 92 96 16938372
  185. [199]Ahn YM Lee KY Kim CE The acute and long-term effectiveness of amisulpride in patients with schizophrenia: results of a 12-month open-label prospective follow-up study Hum Psychopharmacol 2011 26 8 568 577 22139601
  186. [200]Kim EY Kim SH Lee NY Relationship between prolactin levels and subjective endocrine-related adverse effects in patients with schizophrenia receiving long-term treatment with amisulpride Pharmacopsychiatry 2012 45 2 57 63 22411694
  187. [201]Frighi V Stephenson MT Morovat A Safety of antipsychotics in people with intellectual disability Br J Psychiatry 2011 199 4 289 295 21816867
  188. [202]Swainston Harrison T Perry CM Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder Drugs 2004 64 15 1715 1736 15257633
  189. [203]DeLeon A Patel NC Crismon ML Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability Clin Ther 2004 26 5 649 666 15220010
  190. [204]Naber D Lambert M Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism Prog Neuropsychopharmacol Biol Psychiatry 2004 28 8 1213 1219 15588748
  191. [205]Fleischhacker WW McQuade RD Marcus RN A double-blind, randomized comparative study of aripiprazole and olanzapine in patients with schizophrenia Biol Psychiatry 2009 65 6 510 517 18986646
  192. [206]McIntyre RS Yoon J Jerrell JM Aripiprazole for the maintenance treatment of bipolar disorder: a review of available evidence Neuropsychiatr Dis Treat 2011 7 319 323 21655345 PMC3104690
  193. [207]Belgamwar RB, El-Sayeh HG. Aripiprazole versus placebo for schizophrenia. Cochrane Database Syst Rev. 2011;(8):CD006622. PMC12359115 21833956
  194. [208]Chen CY Lin TY Wang CC Improvement of serum prolactin and sexual function after switching to aripiprazole from risperidone in schizophrenia: a case series Psychiatry Clin Neurosci 2011 65 1 95 97 21265942
  195. [209]Park MH Han C Pae CU Aripiprazole treatment for patients with schizophrenia: from acute treatment to maintenance treatment Expert Rev Neurother 2011 11 11 1541 1552 22014131
  196. [210]Takeuchi H Uchida H Suzuki T Changes in metabolic parameters following a switch to aripiprazole in Japanese patients with schizophrenia: one-year follow-up study Psychiatry Clin Neurosci 2010 64 1 104 106 19968829
  197. [211]Lee HY Ham BJ Kang RH Trial of aripiprazole in the treatment of first-episode schizophrenia Psychiatry Clin Neurosci 2010 64 1 38 43 20416024
  198. [212]Glick ID Mankoski R Eudicone JM The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo-controlled, pivotal trials J Affect Disord 2009 115 1–2 18 26 19230981
  199. [213]Mir A Shivakumar K Williamson RJ Change in sexual dysfunction with aripiprazole: a switching or add-on study J Psychopharmacol 2008 22 3 244 253 18308789
  200. [214]Kane JM Meltzer HY Carson WH Jr Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine J Clin Psychiatry 2007 68 2 213 223 17335319

200 of 410 shown

Authors
Peuskens, J., Pani, L., Detraux, J., & De Hert, M.
Affiliations
  • KU Leuven (BE)
  • Italian Medicines Agency (IT)
ORCID
Venue
CNS Drugs
Publisher
Springer Science and Business Media LLC
Published
2014-03-28
Volume
28
Issue
5
Pages
421-53
ISSN
  • 1172-7047 (ISSN-L)
  • 1179-1934
DOI
10.1007/s40263-014-0157-3
PMC
PMC4022988
OpenAlex
W1966949437
Cited by
350
References
446
Citations by year
2026: 6 · 2025: 18 · 2024: 27 · 2023: 23 · 2022: 32 · 2021: 41 · 2020: 29 · 2019: 31 · 2018: 33 · 2017: 31 · 2016: 32 · 2015: 34 · 2014: 12
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
Locations
  • CNS Drugs (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
hyperprolactinemia, antipsychotic drugs, serum prolactin, atypical antipsychotics, asenapine, iloperidone, lurasidone, amisulpride, risperidone, paliperidone, aripiprazole, quetiapine, clozapine, ziprasidone, olanzapine
MeSH terms
Animals, Humans, Hyperprolactinemia, Prolactin, Antipsychotic Agents

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