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European Journal of Endocrinology -18-0682 most common type of secretory pituitary adenoma. pituitary most commontypeofsecretory for -secreting adenomas (), the (DAs) constitute the first-line treatment Introduction risk stratificationandmanagement. all physicianswhoprescribeDAs.Largerprospectivecontrolled clinicalstudiesareneededtodelineateprevalence, prior psychiatrichistory.IncreasedawarenessforICDs, depression, maniaandothertypesofpsychosisisneededby Conclusion: dose anddurationoftherapydidnotcorrelatewithoccurrence ofpsychiatricpathology. , whichimprovedafterdiscontinuationandadministrationofpsychiatricmedications.Gendertype DA, DA discontinuation.Incasereports,therapywastemporallyassociatedwithseveredepression,manicepisodes or hypersexuality mostlyinmen.MultipleICDsweresometimesreportedthesamepatient,usuallyreversibleafter scores thannormoprolactinemiccontrols.Impulsecontroldisorders(ICDs)werereportedinbothgenders,with quality oflife,,depressionandcertainpersonalitytraits.PatientsreceivingDAshadhigherimpulsivity small numbersofpatients.Comparedwithcontrols,patientshyperprolactinemiagenerallyhadworse nonfunctioning pituitaryadenomas.Therewerefewprospectivestudies,with/withoutcontrolgroup,thatincluded Results: of psychiatriccomplicationswerealsoreviewed. psychological profileofDA-treatedpatientswithhyperprolactinemiaandprolactinomas.Caseseriescasereports Methods: exacerbations ofpriorpsychiatricdisease. Recently, anincreasingnumberofreportsemphasizedDAs’psychologicalsideeffects,either Background: Abstract Birmingham, Alabama,USA,and and MetabolismVeteranAffairsHospital,DepartmentofMedicineNeurosurgery,UniversityAlabamaat Neurosurgery, StanfordUniversitySchoolofMedicine,Stanford,California,USA, Portland, Oregon,USA, Departments ofMedicine,NeurosurgeryandNorthwestPituitaryCenter,OregonHealthScienceUniversity, University SchoolofMedicine,Atlanta,Georgia,USA, 1 Adriana G Ioachimescu adenomas hyperprolactinemia andprolactin-secreting treatment inpatientswith Psychological effectsofdopamineagonist Division ofEndocrinology,DiabetesandMetabolism,DepartmentsMedicine, NeurosurgeryandEmoryPituitaryCenter, https://doi.org/ https://eje.bioscientifica.com Clinical Study Moststudieswerecross-sectionalandhadacontrolgroupofhealthyvolunteersorpatientswith Reviewofprospectiveandretrospectivestudies(PubMed1976,September2018)evaluatingthe PatientswithhyperprolactinemiareceivingDAsmaydevelop changesinmoodandbehaviorregardlessof 10.1530/EJE Dopamineagonists(DAs)arethemaintreatmentforpatientswithhyperprolactinemiaandprolactinomas. 3 -18-0682 Division ofEndocrinology,GerontologyandMetabolism, DepartmentofMedicine and 1 , Maria Fleseriu 1 © 2019EuropeanSociety ofEndocrinology A GIoachimescuandothers 5 Veteran Affairs,PaloAlto,California,USA 2 Division ofEndocrinology, DiabetesandClinicalNutrition, 2 Printed inGreatBritain , Andrew RHoffman tumor size( decrease galactorrhea,lower prolactinlevelsanddecrease Treatment isrecommendedtorestoregonadalfunction, dopamine agonists Psychological effectsof 4 Published byBioscientifica Ltd. Division ofDiabetes,Endocrinology 3, 5 , T Brooks Vaughan III 1 , 2 ). Treatment islongterminmostpatients( Downloaded fromBioscientifica.com at09/27/202102:03:01AM 4 and de novo (2019) Endocrinology European Journalof [email protected] Email to AGIoachimescu should beaddressed Correspondence Laurence Katznelson 180 180 oras :1 , 31–40

31 –40 3 via freeaccess ). 3

European Journal of Endocrinology https://eje.bioscientifica.com involved inthecontrolofprolactin secretion( pleasure andaddiction (3)tuberoinfundibular, the rewardsystem,involved intheregulationofbehavior, motor functions,(2)mesocorticolimbic, alsoknownas pathways:(1) nigrostriatal,involvedin learning andprolactincontrol.Therearethreemain important formotorfunction,motivation,reinforcement gland areinvolved.Dopamineisaneurotransmitter entwined, especiallywhenthehypothalamusandpituitary The endocrinesystemandmentalhealthareclosely dopamine agonists with prolactinomastreated Mechanism ofpsychiatricdisturbancesinpatients for relevanceandsignificance. language articleswerereadandreviewedbytheauthors or ‘hypersexuality’ ‘depression’ or ‘mania’. AllEnglish and ‘psychiatricdisorders’,‘impulsecontroldisorders’ ‘dopamine agonists’or‘’‘’ through July 2018 was conducted using the search terms ofMedicinePubMedsearchA USNationalLibrary Methods in patientstreatedwithDAsforhyperprolactinemia. management ofpsychologicaldisturbancesencountered regarding mechanisms,clinicalpresentation,courseand problems asaresultofDAtherapy. management ofpatientsexperiencingpsychological Moreover, therearenospecificguidelinesforthe symptoms, and asa result, underreporting is likely. aware oftheassociationbetweenDAsandpsychiatric psychiatric disease.Manyendocrinologistsarenot DA therapyorasexacerbationsofpreviouslyknown (ICDs) havebeenreportedeither nightmares, paranoiaandimpulsecontroldisorders hallucinations,hyperactivity,auditory insomnia, Psychosis, mania,anxiety, depression,confusion, also beendescribed,manyasisolatedcasereports. addition, avarietyofpsychologicalsideeffectshave dizziness, orthostatichypotensionandheadaches.In other thantheUnitedStates. another DA currently or previously used in some countries approved fortreatmentoftype2diabetes.Quinagolideis this indicationin the United States; bromocriptine is also Bromocriptine andcabergolinearecurrentlyapprovedfor Clinical Study In thisreview, weexaminethecurrentknowledge The mostfrequentadverseeffectsofDAsarenausea, A GIoachimescuandothers de novo afterstarting 4 ). the drug’s capacitytocrosstheblood-brainbarrier, which patients receivingDAsforPDandRLS. (P-gp) is a transport molecule encoded by the is controlledbytransportermolecules.P-glycoprotein1 D3 agonists were associated with more ICDs ( with bromocriptineandcabergoline( syndrome (RLS), have a higher affinity for D3 compared approved forParkinson’s disease(PD)andrestlessleg than bromocriptine( andcabergolinehaveloweraffinityforD1 to D2andwithloweraffinityD1D3receptors. cabergoline andquinagolidebindwithhighaffinity neuropsychiatric sideeffectsofDAs( certain neuronalpathway, whichcanexplainsomeofthe is generallynotspecifictoonereceptortypefroma in highdensitythemesolimbiccortex.DAbinding in thestriatalpathway( system ( dopamine type2(D2)receptorsinthetuberoinfundibular altered baselinetoneofdopaminergic activity. different classes ofDAreceptorsin the brain,aswell understood. Theyentailspecific affinitiesofthedrugson treated with DAsarecomplex and incompletely psychiatric disturbancesin patients withprolactinomas humiliation ( in inducedsituationsthatevokedfeelingsofrageand normal subjectshavereportedsurgesinserumprolactin Prolactin levelscanincreaseduringstress,andstudies in to teasethemapartastheyoftenoccursimultaneously. steroid levelsorhyperprolactinemiaitself.Itisdifficult central dopamine depletion ( determined. Several factors havebeeninvoked, including individuals withnormalprolactinlevelsremainstobe susceptible to neuropsychiatric complications of DAs than rs2032582 associatedwithdizzinessduringDAtherapy( associated withfatigueandsleepdisorders,whileSNP during cabergolinetherapy. ABCB1SNPsrs1045642were fatigue, dizziness,sleepdisordersandheadacheschanged patients completedquestionnairestodeterminewhether study of79patientswithprolactinomas.Inthelatter, ABCB1-knockout mousemodelstudyandacase-control therapy. Thishypothesisissupportedbyanexperimental influence thepredispositiontoCNSside effectsfromDA influence oralterthefunctionofP-gpproteinandcould the blood.Geneticpolymorphismsof that transportssubstratesreleasedfromtheneuronbackinto dopamine agonists Psychological effectsof Central nervous system (CNS) side effects depend on system(CNS)sideeffectsdependon Central nervous DAs exerttheirendocrineeffectsbybindingto In summary, themechanisms ofpsychologicand Whether patients with hyperprolactinemia are more 5 ). BothD2andD3receptorsarealsoexpressed 12 ). 8 ). Pramipexoleandropinirole,DAs Downloaded fromBioscientifica.com at09/27/202102:03:01AM 6 ), andD3receptorsarepresent 5 ), decreased gonadal sex 180 9 ). Notably, selective 7 ). Bromocriptine, :1 ABCB1 ABCB1 gene may genemay 10 gene gene 32 ) in 11 via freeaccess ). European Journal of Endocrinology not correlatewitheithercurrent DAuseordurationof Of note, the extent of psychological impairment did and totalscoresforHADS comparedwithcontrols. patientsalsohad worseanxiety, depression patients whencompared with controls.Furthermore, MFI-20 wereallimpairedinthehyperprolactinemic physical, fatigue,activityandmotivationsubscaleson and socialisolationsubscalesonNHP, andgeneral problems onSF-36,theenergy, emotional reaction social functioningandrolelimitationsduetophysical emotional, mentalandsocialaspects.Thesubscalefor different dimensionsofqualitylife,includingphysical, Hospital Anxiety and Depression Scale-HADS) covered and SF-36, MultidimensionalFatigueInventory-MFI-20 related questionnaires(NottinghamHealthProfile-NHP, control groupconsistedof183subjects.Thehealth- age andsamesex(arelative,friendorneighbor).The were askedtoprovideacontrolpersonofcomparable invited tocomplete questionnaires (62 accepted) and or quinagolideformicroprolactinomas,81patientswere study ofwomentreatedwithbromocriptine,cabergoline during DAtreatment.Inasingle-centercross-sectional functions in hyperprolactinemic patients atbaseline and systematic evaluationofneurocognitiveandpsychological weresimilartocontrols( physical summary physical functioning,bodilypain,generalhealthand emotional, mentalhealthandthesummary. The were rolephysical,vitality, socialfunctioning,role compared with healthycontrols. The domainsaffected Short FormSurvey, ofhealth) apatientreportedsurvey had lowerscoresontheSF-36questionnaire(36-Item ( and hostilitythannormoprolactinemiccontrolswith were morelikelytoexperiencedepression,anxiety study of ten women with hyperprolactinemia, patients did notreproducethesefindings( bromocriptine for6–12 months (withoutacontrolgroup) a prospectivestudyinninepatientstreatedwith eight patientswithhyperprolactinemia( blind cross-over placebo-controlled design and included these symptoms( bromocriptine wasassociatedwithameliorationof and hostility( and indicatedincreasedlevelsofanxiety, distress Early reportsinthe1970–1990sincluded3to14patients with hyperprolactinemia Psychological profileofpatients Clinical Study There arefewcontrolledclinicalstudiesthatreport A studyin39patientswithuntreatedprolactinoma 17 13 ). , 15 14 , , 16 15 , , 17 16 ). Onestudyhadadouble- ) andthattreatmentwith A GIoachimescuandothers 18 ). Inacross-sectional 16 19 ). However, ). more dependentthan31non-treatedpatients.Inaddition, 55 patientsreceivingDAsshowedthatthesewere compared with patients with NFA. Asubgroup analysis in lower scoresonnoveltyseekingsubscaleimpulsiveness extraversion, increasedshynesswithstrangersand with prolactinoma had higher neuroticism, reduced fatigability andastheniacomparedwithcontrols.Patients neuroticism, increasedfearoruncertaintyand tumorshadincreased controls. Allpatientswithpituitary adenomas(NFA)with nonfunctioningpituitary and172 with prolactinomawerecompared58patients Temperament andPersonalityQuestionnaire. Patients Eysenck PersonalityquestionnaireandtheCloninger a distinctdopaminergic personality profileusing the psychological impairments( women correlatedwiththedegreeofqualitylifeand nor the presence of hypogonadism in premenopausal therapy. Inaddition,neithertheserumprolactinlevel, needed toclarifythisissue. hyperprolactinemia. Further largecontrolledstudiesare reported mentalandphysical healthofpatientswith clear whether DA therapy favorably influences the self- also indicateincreasedanxiety anddepression.Itisnot compared withcontrol subjects. Some, butnotallstudies quality oflife,anddifferentpersonalityprofiles with hyperprolactinemiaappeartohavedecreased and paranoidideationafter12 monthsoftreatment( screened positiveforobsession,interpersonalsensitivity treatment. Morepatientsintheprolactinomagroup monthsofcabergoline inter-group differencesafter3 anxiety orparanoidideation.Similarly, there wereno interpersonal sensitivity, psychoticism,hostility, phobic regarding somatization,anxiety, obsession,depression, At baseline,therewerenodifferencesbetweengroups and Beck AnxietyInventory.Beck Depression Inventory Impulsiveness Scale,SymptomCheckListquestionnaire, Minnesota ImpulsiveDisordersInterview, Barratt prolactinoma and 32 healthy controls with the revised not changeafterDAtherapyinthisstudy. avoidance scores. Interestingly, these personality traits did with decreased novelty seeking and increased harm low dopaminergicactivity, whichhasbeenassociated that patients with hyperprolactinemia have the theory persistent hyperprolactinemia ( and extravagancetendenciescomparedwiththose excitability levels had lower novelty seeking, exploratory treated patients who achieved normal serumprolactin dopamine agonists Psychological effectsof A study in 86 patients with prolactinomas described In summary, basedonavailable literature,patients A recentstudyevaluated25patientswith Downloaded fromBioscientifica.com at09/27/202102:03:01AM 20 ). https://eje.bioscientifica.com 21 ). This study supports 180 :1 33 22 via freeaccess ). European Journal of Endocrinology https://eje.bioscientifica.com libido, sexualthoughts, frequencyandhigh-risk prolactinomas ( case reportsofICDduring DA therapy administered for took bromocriptine. yearspreviouslywhenshe not havetheseproblems25 000.Ofnote,thepatientdid a financiallossof$700 depression andparanoiddelusions,havingincurred cabergoline ( 2007 ina47-year-oldwomantakinglowdose of treated withDAsforprolactinomawasreported in lower, at7.1–11.4% ( PD ( least 3consecutivemonths( in specificpopulations:39.1%patientstreatedforat ICDs between2.6and34.8%( were treatedwithDAs,thereisareportedprevalenceof cabergoline and bromocriptine. In patients with PD who and ropironole have higher D3 affinity than RLS supporttheinvolvementofmesolimbicD3receptors; of reportsinpatientsreceivingDAtherapyforPDand hyperprolactinemia ( ICDs weretreatedforPD,24%RLSand3.5% FDA indicatedthat62%ofthepatientsexperiencing A recentreviewofDA-associatedICDsreportedtothe after 2006andalmostreachedaplateau2009( physicians. TheFDAreportingincreasedprogressively There wasaslightlyhigherreportingbypatientsthan age of55andmalegenderpreponderance(65.8%). ( ropirinole (188), cabergoline (56) and bromocriptine accounted for710events(45%):pramipexole(410), 2012 identified 1580 ICD events. Of them, DA therapy FDA Adverse Event Reporting System between 2003 and is estimatedat8%( social andfinancialconsequences. or sorting objects). ICDs can be serious with significant mechanical tasks(i.e.assemblinganddisassembling punding. Pundingisdefinedascompulsiverepetitive compulsive medicationuse,obsessivehobbyingand hypersexuality, bingeeating,compulsiveshopping, or others.Manifestationsincludepathologicalgambling, temptation toperformanactthatisharmfuloneself disorders’ definedasthefailuretoresistanimpulseor The ICDsare‘disruptive,impulsecontrolandconduct control disorders Dopamine agonisttherapyandimpulse 30 Clinical Study ). Thestudyindicatedaffectedpatientshadamedian The firstcaseofpathologicalgamblinginapatient The prevalence of ICD in the general population Pathologic hypersexuality may includeincreased 26 ). In patients treated for RLS, ICDs prevalence was 27 ). She sought medical attention for major 24 , 27 4 24 7 al 1 Table , ). ). Aretrospectivestudybasedon 28 ). Thesignificantlyhighernumber , 29 25 summarizestheindividual , 4 30 ) and58.3%inearly-onset ). Higherrateswerenoted A GIoachimescuandothers , 31 ). 23 ). than thenonresponders.Additional phonediscussions between menandwomen,but theresponderswereolder mean age.Theoverallresponse rateswerenotdifferent than theprolactinomagroup (64vs55%),withasimilar in eachgroup.TheNFA groupincludedmorewomen sentto200 patients selected throughapostalsurvey prolactinomas and70patientswithNFA. Patientswere aimed atICDdetectionin77patientswithDA-treated include acontrolgroup. that of the generalpopulation, but unfortunately did not study found that ICDs prevalence was comparable to with resolutionofsymptoms,whichdidnotrecurafter hypersexuality anddecreasedthedoseorstoppedDA, normal testosteronelevels.Sixpatientswerebotheredby increased duringDAtherapy, withallpatientsachieving the lowerhalfofnormalrangeintwopatients,and (75 bromocriptine (0.625–2.5 ( ofpsychiatricdisease prolactinoma andnopriorhistory ‘dopa-testotoxicosis’ intheirreportofeightmenwith to thehypersexuality. DeSousa of in men taking DA therapy may contribute pathway stimulationasdootherICDs;also,increasinglevels use of recreational drugs). The mechanism entails reward engagement inprostitution,promiscuityandtheft reduced workperformanceandillicitactivities(e.g., which canleadtorelationshipproblems,financialloss, may not be forthcoming in reporting these manifestations, sexual activities.Duetotheirpersonalnature,patients severe hypersexualityandcompulsiveeating( doses. Manifestationsincludedpathologicalgambling, male patients(10%),bothtreatedwithrelativelylowDA (MIDI).ICDswereidentifiedintwo Disorder Interview study evaluated20patientswiththeMinnesotaImpulse treated with DAs forprolactinomas. A cross-sectional term ‘dopa-testotoxicosis’doesnotseemappropriate. symptoms resolvedafterstoppingtheDA.Hence, testosterone levelswerenotsupraphysiologicandthe disruptive hypersexuality in men undergoing DA therapy, quinagolide ( with cabergolineorbromocriptine( are fewcasereportsofhypersexualityinwomen:three DA dosedecreasedorwasstopped( daily) confirmedresolutionofhypersexualityafterthe cabergoline (0.5–2 case reportsinmenwithprolactinomaswhoreceived surgery.testosterone replacement or pituitary Additional dopamine agonists Psychological effectsof 32 ). Patientsreceivedcabergoline(0.5–1 μ Bancos There arefewsystematicstudiesofICDsinpatients g daily).Testosterone levelswerelowinsixand et al Table 1 . conductedthelargestcasecontrolstudy mg weekly)orbromocriptine(7–15 ) ( 31 Downloaded fromBioscientifica.com at09/27/202102:03:01AM ). Whiletherearemorereportsof mg daily)and/orquinagolide et al 29 180 . proposedtheterm 33 , 33 :1 ) andonewith , 34 mg weekly), , 35 34 ). There ). This 34 mg via freeaccess European Journal of Endocrinology on DA therapy, 10 untreated hyperprolactinemic patients in a cross-sectional design: 10 hyperprolactinemic patients ICDs thanmenwithNFAs (27.7vs3.7%)( with prolactinomas had almost 10 times higher risk of risk ofICDperse,subgroupanalysisshowedthat men (12.99 vs2.87%).Whilegenderdidnotcorrelatewiththe prolactinomas, which occurred less frequentlyincontrols predominant ICDencounteredinpatientswithDA-treated high ICDprevalence (17.14%). Hypersexuality wasthe ICDs. Interestingly, patientswithNFA alsohadarelatively shrinkage werenotassociatedwiththedevelopment of of DAused,tumordiameterandpost-treatment patients withprolactinomas.Durationoftreatment,type interview. OneormoreICDs werefoundin24.68%of 18% patientswerenotreceivingDAsatthetimeof week) andbromocriptine(29%,8.75–70 consisted ofcabergoline(53%patients,0.25–4 months(range5–455)and a mediandurationof94 prior toparticipatinginthestudy. DAtreatmenthad months with prolactinomaswerediagnosedatleast12 andtoobtaindetailsregardingsymptoms.Patients survey were undertaken to confirm thepositiveanswers tothe Micro, microadenoma.y,years;†,depressionaftermarriage. ( ( ( ( ( ( ( Study disorders (ICDs). Table 1 24 35 30 28 29 27 31 Clinical Study ) ) ) ) ) ) ) Barake Giant prolactinoma 19 y, M, Giant prolactinoma 19 yM, Prolactinoma 16 y, F, Micro Middle age,F, Micro 50 y, F, Micro 44 y, F, Micro 47 y, F, endocrine diagnosis Age, sex Individual casereportsofpatientswithprolactinomawhodevelopeddopamineagonist-associatedimpulsecontrol et al (M/F) . ( 36 , ) evaluatedimpulsivityin30 subjects disease History ofpsychiatric A GIoachimescuandothers (Y/N) Y † N N N N N N mg/day), while 33 ). Cabergoline then Bromocriptine Cabergoline Bromocriptine Bromocriptine Cabergoline Quinagolide Cabergoline DA regimen 1.5 mg/week 20 mg/day 2.5 mg/week 5 mg/day 0.25 mg/week 225 mg/day 0.25 mg/week cabergoline then quinagolide then mg/ patients onDAsdisplayeda higherdegreeofimpulsivity 7–192). Inthiscross-sectional study, hyperprolactinemic months (range with a median therapy duration of 33 weekly cabergoline dose was 1.1 one patient who receivedbromocriptine. The mean Treatment withDAsconsisted ofcabergolineinallexcept immediate rewardsoverpossiblylargerbutdelayedones. measure ofdelaydiscountingorpreferenceforsmall,but and theExperientialDiscountingTask (EDT), areal-time instrument thatinvolvesactualrisk-takingbehavior Balloon AnalogRiskTask (BART), a computerized two validatedpsychometrictestsofimpulsivity:the planning (lack of forethought). Patients also completed or concentrate), motor (acting without thinking) and non- in threedomains:attentional(inabilitytofocusattention questionnaire thatmeasurestheconstructofimpulsivity and theBarrattImpulsivenessScale(BIS-11),a30-item measuring responsestoreward(BAS)andpunishment(BIS Activation System (BIS/BAS), a 24-item questionnaire Self-report measuresincludedtheBehavioralInhibition/ ofsubstanceusedisorderswereexcluded. or ahistory tumors.Patientswithpsychiatricdisorders of pituitary and 10normoprolactinemiccontrolswithothertypes dopamine agonists Psychological effectsof 3 y 2 y 2 y 6 y 5 y 1 y exposure Length of Shortly after therapy starting Hypersexuality Financial debt Gambling Separation frompartner Worsened depression Compulsive shopping, Divorce proceedings Loss of$100 000 Gambling, hypersexuality Loss of10 000euro Gambling, hypersexuality, Loss of$700 000 Gambling, major consequences Manifestations andsocial Loss of20 000euroand Gambling, depression gambling andeating mania delusions depression, paranoid prison sentence Downloaded fromBioscientifica.com at09/27/202102:03:01AM https://eje.bioscientifica.com mg (range 0.5–2 180 Improved during Resolved after Improved 3 weeks Resolved after Resolved after Resolved after Outcomes Improved with :1 one-month trial bromocriptine stopping DA after stopping stopping DA stopping DA stopping DA continued) (cabergoline and citalopram psychotherapy off DA mg), 35 via freeaccess European Journal of Endocrinology https://eje.bioscientifica.com can be attempted, while the patient is carefully monitored can be attempted, whilethepatientiscarefullymonitored DA or another DA approved for use in hyperprolactinemia Therefore, incaseofmildmanifestations, asmallerdoseof instances, ICDsonlydeveloped withonetypeofDA( reversible afterDAstopped ordosedecreased;insome ICD manifestations reported in the literature were mostly initiation andrevisitthisissueatfollow-upvisits.The physicians discuss the risk of ICDs at the time of DA therapy or resolvedICDs( or psychiatric medications wereassociated with improved even reducingthedosealongwithaddingpsychotherapy DA therapy( reported patientsdevelopedmultipletypesofICDsduring 28 cases andledtoreoccurrenceofICDinsomepatients( one DAwithanotherhasbeenattemptedinafew Challenging patientswhoexperiencedICDswhiletaking available atthetimeofreportindifferentcountries. not possiblebecauseofdifferenttypesDAsthatwere treatment. ComparingtheriskbetweendifferentDAsis taking cabergoline)( (suggested byonestudythatincludedninepatients DA therapyassociationwithICDsisdose-dependent exclusion criterioninsomestudies.Itisunclearwhether may increasetheriskofICD;however, thiswasan psychiatric disease,inparticularanxietyanddepression, of ICDs did nothave a gender predilection. Preexisting men thaninwomenwithprolactinoma,butothertypes be shown. More cases of hypersexuality were reported in and ICDdevelopmentinprolactinomapatientscouldnot hypersexuality ( PD, especiallywithregardtopathologicalgamblingand Young ageand malegenderwereassociatedwithICDsin in patientswithprolactinomatreatedDAtherapy. less severemanifestationsoccurred( to smallerdoseofthesameDA,eithernosymptomsor discontinuation oftheDA.Whenpatientswereexposed associated withDAsuse,whichimprovedorresolvedafter Two casesofICDsconsistinghypersexuality(8%)were for the presence of ICDsand other psychiatric disorders. with prolactinoma,31NFA and32healthycontrols study ( EDT testinhyperprolactinemicDA-treatedgroupthis dose wasassociatedwithhigherimpulsivechoicesonthe and tonormoprolactinemic controls. A highercabergoline compared tobothuntreatedhyperprolactinemicpatients in theattentionsubscaleofBIS-11questionnaireas Clinical Study ). Itisimportanttonotethatapproximately33%of Based on the data accumulated, we suggest that Based onthedataaccumulated,wesuggestthat The dataaresparseregardingriskfactorsforICDs Celik 36 ). t al et 32 . ( , 4 22 33 ). However, acorrelationbetweenage 24 ) prospectivelyevaluated25patients ). Finally, discontinuationofDAsor , 36 27 ) orrelatedtothedurationofDA , 29 , 31 , 32 A GIoachimescuandothers , 22 33 ). , 34 , 35 ). 24 , 27 24 ). ). , treatment withdopamineagonistsforprolactinoma Psychiatric disordersotherthanICDsduring can beconsidered. and between pharmacologictreatmentofhyperprolactinemia further study. Ifthetemporalassociationisdemonstrated patients withprolactinomawhodevelopedICDsrequires replacescabergolineorbromocriptinein prolactinomas arenotavailable.Theapproachwhereby disease ( coexistence ofaprolactin-secretingtumorandpsychiatric to improveprolactinsecretioninsomepatientswith partial dopamineagonistD2activityandhasbeenshown disorder. Unlikemostantipsychotics,aripiprazolehas disorder, majordepressivedisorderandautismspectrum aripiprazole hasbeenapprovedforschizophrenia,bipolar by bothendocrinologyandpsychiatry. Theantipsychotic prior toDAtherapywas negative.Interestingly, (onepatient,1.2 (four patients,dosesranging from7.5to60 prolactinoma ages 20–58 treated with bromocriptine in eight patients, among them five women with treated withDAs.Psychoticreactionswereidentified a 600patientswithacromegalyorhyperprolactinemia Turner when usingDAs,evenintheabsenceofapriorhistory. of thepotentialforprecipitationpsychiatricdisease Inclinicalpractice,oneshouldalwaysbeaware 6 years. to The durationofexposuretoDAsrangedfrom4 days ofpsychiatricdisease, othersdidnot. had apriorhistory resection oftheprolactinoma( as well.Onepatientwastreatedwithtranssphenoidal one case,anantipsychoticmedicationwasinitiated catatonia. Inmostcases,theDAwasstopped.allbut included severedepression,mania,psychosisandeven effect hyperprolactinemia.Thepsychiatricdisturbances patients hadprolactinomasandsomeaNFA withstalk hyperprolactinemia rangedfrom45to9400 ( with themajorityoccurringinwomentakingcabergoline worth presenting). bias (cliniciansawareofthispossibilitymaynotconsiderit absence ofdirectquestioningandbecausepublication association, aspatientsmaynotbeforthcominginthe number isquitesmall.Thislikelyanunder-reported depression, manicepisodesorpsychosis,buttheoverall There arereportsofDAuseassociatedwithsevere dopamine agonists Psychological effectsof 37 , Clinical studiesonthistopicaresparse.In1984, de novo 38 , et al 37 39 , ICDs, surgical treatment of the pituitary tumor tumor ICDs,surgicaltreatmentofthepituitary , 38 . ( 40 ). Efficacy and safety studies in patients with ). Efficacyandsafetystudiesinpatientswith 47 , ) performeda retrospective analysisof 41 Table 2 , 42 , Downloaded fromBioscientifica.com at09/27/202102:03:01AM 43 summarizesthesecasereports, mg daily).Psychiatrichistory , 44 , 43 45 ). Whilesomepatients , 180 46 ). Theseverityof :1 ng/mL, some mg) or 36 via freeaccess

European Journal of Endocrinology

Table 2 Individual case reports of patients with hyperprolactinemia who developed depression, mania or psychosis while taking dopamine agonists. Clinical Study

Age, sex (M/F), History of psychiatric Prolactin Length of Study endocrine diagnosis disease (Y/N) level (ng/mL) DA regimen exposure Manifestations Outcomes

(44) Unknown Unknown Unknown Bromocriptine Unknown Psychosis Unknown (43) 53 y, M, N 933 Bromocriptine 2.5 mg/day 4 days Psychosis Stop bromocriptine, pituitary surgery Macro (42) 25 y, F N 300 Bromocriptine 10 mg/day 6 y, intermittent Psychosis Stop bromocriptine, initiate (40) 23 y, F, Schizophrenia 171 Cabergoline 4 y Hallucinations, delusions, catatonia Stop cabergoline, initiate aripiprazole, symptoms Macro treated with resolved after 2 weeks, prolactin normalized (41) 39 y, F, N 9400 Bromocriptine 2.5 mg/ 5 y Depression, psychosis, delusions Initiate aripiprazole, continue bromocriptine; Macro day, stopped 2 months symptoms resolved after 4 weeks prior to presentation (45) 44 y, F, Y Unknown Cabergoline 3 mo Psychosis Resolved immediately after stopping cabergoline Unknown Depression

(39) 32 y, F, N 48.1 Cabergoline 0.25 mg/ 2 y Worsening depression, delusions, hallucinations Resolved after stopping cabergoline and initiating A GIoachimescuandothers Micro week aripiprazole (38) 30 y, F, Y 51.7 Bromocriptine 5/day* ‘Short’ Worsening depression, insomnia, delusions, Resolved after stopping bromocriptine and Micro Depression hallucinations initiating aripiprazole (39) 34 y, F, Y 45 Cabergoline 0.5 mg/week 1 mo Worsening depression, mania, disinhibition, Stop cabergoline, initiate aripiprazole Micro Depression or spending bipolar disorder (49) 26 y, F, N Unknown Cabergoline 0.5 mg/day ‘Short’ Mania with psychotic features (grandiose and Improved 3 weeks after stopping cabergoline and PP galact paranoid delutions) initiating aripiprazole (46) 25 y, F, N 60 Cabergoline 1 mg/week 6 mo Mania Resolved 4 weeks after stopping cabergoline and Micro initiating lithium

*Patient was previously treated with cabergoline which caused emotional lability, insomnia and worsened depression. Macro, macroadenoma; Micro, microadenoma; PP galact, postpartum galactorrhea; y, years; mo, months as the psychiatric medications of choice in this setting as thepsychiatricmedicationsofchoiceinthissetting lactinemia inthesettingofknownpsychoticdisorders, Particularly challengingisthetreatmentofhyperpro­ treated withantipsychoticmedications Treatment ofhyperprolactinemiainpatients questionnaire ( scores ofSCL-90-R(SymptomChecklist–90–Revised) anxiety subscalesandhighergeneralseverityindex sensitivity, paranoidideation,hostility, phobic was positively correlated to obsession, interpersonal after 12 months ofDAtherapy. ThecumulativeDAdose obsession, interpersonalsensitivity, paranoidideation patients withprolactinomascreenedpositivefor NFA and32healthycontrols.Thestudyfoundmore with prolactinomatreatedcabergoline,31 Celic all fivepatientsdevelopedparanoidpsychosis.( ( who had bothmacroprolactinomasand schizophrenia bromocriptine or quinagolide was successful in patients cases normalized. The combination of aripiprazole and by 74%inpatientstakingaripiprazole ( ( treatmentinmanyofthe reportedcases a satisfactory activity. other , aripiprazole has partialdopamine unique advantagesinthisspecificsetting( Theantipsychoticaripiprazole maypossess observed. monitored. Similarly, tumorscanbeclosely smallpituitary taking gonadalreplacement)theprolactinlevelscanbe In asymptomaticpatientswithouthypogonadism(or considered incollaborationwiththepatient’s psychiatrist. medications thatdonotraiseserumprolactinlevelscanbe necessary. Wheneverpossible,alternativepsychiatric evaluation forgalactorrheaandhypogonadismis In patientswithdrug-inducedhyperprolactinemia, gland should be considered. an MRI of the pituitary safe withregardtothepatient’s psychiatriccondition, mental health specialist ( levels, whichmustbedoneinconsultationwiththepatient’s andrepeating serumprolactin offending drugfor3 days recommendations suggest withdrawal ofany potentially adenoma shouldbecarefullyconsidered.Current medication-induced hyperprolactinemiavspituitary cause hyperprolactinemia.Thedifferentialdiagnosisof commonly reportedpsychotropicmedicationsthat prolactin ( are oftendopamineantagonistswhichmayfurtherraise dopamine agonists Psychological effectsof 41 37 , , 51 38 t al et ); while these results are encouraging, it is not known ); whiletheseresultsareencouraging, itisnotknown , 39 7 , . ( ). and are the most ). Risperidoneandhaloperidolarethemost 40 22 , 22 ) prospectivelyevaluated25patients 41 al 2 Table ). , 49 ). Prolactin decreased on average ). Prolactindecreasedonaverage Downloaded fromBioscientifica.com at09/27/202102:03:01AM illustrates that aripiprazole was illustratesthataripiprazolewas 1 ). If this approach does not seem ). If this approach does not seem https://eje.bioscientifica.com 180 :1 50 ) and in many ) andinmany 48 ). Unlike ). Unlike 37 47 via freeaccess ). ).

European Journal of Endocrinology https://eje.bioscientifica.com the public,commercialornot-for-profit sector. This research did not receive any specific grant from any funding agency in Funding be could that interest of conflict perceived asprejudicingtheimpartialityofthisstudy. no is there that declare authors The Declaration ofinterest of addingDAtherapy. individualized treatmentforprolactinomasandthesafety with mentalhealthspecialistsisrequiredtoassess with knownpsychiatricdisease,aclosecollaboration mania and other types of psychosis. For patients aware ofthepotentialoccurrenceICDs,depression, consequences. Physicians whoprescribe DAs shouldbe and severitymayhavesignificantmedicalsocial inspectrum hyperprolactinemia andprolactinomasvary Psychological changesinpatientstreatedwithDAsfor Conclusions complications ofDAtherapy. recommendations regardingmanagementofpsychiatric tomakespecificclinical prospective studiesarenecessary that includesneuropsychologyandpsychiatry. Further care patients wouldbenefitfromamultidisciplinary are encouraged.Ifsuchalterationswereidentified,the questions about changes in mood and behavioral changes or psychiatric medications. At follow-upvisits, direct ofICDs,depression,anxiety prior orcurrenthistory physicians mayusedirectquestioningregarding best suitedforpatientswithprolactinomas,the further research identifiesthestandardizedquestionnaires when necessary.communication with psychiatry Until ofpsychiatricdisease,andtoinitiate thorough history Before prescribingDA,itwouldbeimportanttotakea societal consequencesthatmayoccurduringDAtherapy. patients isworthwhilegiventhesignificanthealthand affected patients are not well defined. Counseling all used forhyperprolactinemiaandtheriskprofileof The prevalenceofpsychiatriccomplicationsfromDAs Advice forclinicalpractice manifestations coexistentpsychiatricdisease( was usedinsomecasesthesettingofmasseffect be expected.Finally, surgicaltherapyforprolactinoma whether thesamedegreeoftumorinvolutionwould Clinical Study A GIoachimescuandothers 52 , 53 ). References

dopamine agonists Psychological effectsof 16 15 14 13 12 11 10 17 2 1 6 5 4 9 8 7 3 Molitch ME. Diagnosis and treatment of pituitary adenomas:areview.Molitch ME. Diagnosisandtreatmentofpituitary Chanson P &Maiter D.Prolactinoma.In Melmed S, Casanueva FF, Hoffman AR,Kleinberg DL,Montori VM, Ghahremani DG, Lee B,Robertson CL,Tabibnia G, Morgan AT, De Ben-Jonathan N &Hnasko R.Dopamineasaprolactin(PRL) Grall-Bronnec M, Victorri-Vigneau C, Donnio Y, Leboucher J, Zacur HA, Chapanis NP, Lake CR,Ziegler M&Tyson JE. Kellner R, Buckman MT, Fava GA&Pathak D.Hyperprolactinemia, Fava GA, Fava M,Kellner R,Serafini E&Mastrogiacomo I. Sobrinho LG. Prolactin,psychologicalstressandenvironmentin Athanasoulia AP, Sievers C,Ising M,Brockhaus AC,Yassouridis A, Seeman P. Parkinson’s diseasetreatmentmaycauseimpulse-control Ahlskog JE. Pathologicalbehaviorsprovokedbydopamineagonist Barlier A &Jaquet P. Quinagolide–avaluabletreatmentoptionfor Noronha S, Stokes V, Karavitaki N &Grossman A.Treating Fava M, Fava GA,Kellner R,Buckman MT, Lisansky J,Serafini E, Buckman MT &Kellner R.Reductionofdistressin JAMA B978-0-12-804169-7.00016-7) 467–514. EdSMelmed.Elsevier, 2017. (https://doi.org/10.1210/jc.2010-1692) ofClinicalEndocrinologyand Metabolism Journal hyperprolactinemia: anEndocrineSocietyclinicalpracticeguideline. Schlechte JA, Wass JA &Endocrine S.Diagnosisandtreatmentof Journal ofNeuroscience Journal and relatedactivityinfrontostriatalneuralcircuitry inhumans. Striatal dopamineD(2)/D(3)receptorsmediateresponseinhibition Shetler N, Brown AK,Monterosso JR,Aron AR,Mandelkern MA org/10.1210/edrv.22.6.0451) inhibitor. s40264-017-0590-6) association. Dopamine agonistsandimpulsecontroldisorders:acomplex Rousselet M, Thiabaud E, Zreika N, Derkinderen P & Challet-Bouju G. Gynecology neuroendocrine function. Galactorrhea-amenorrhea: psychologicalinteractionwith 759–763. distress, andhostility. org/10.1159/000287535) Psychotherapy andPsychosomatics Depression hostilityandanxietyinhyperprolactinemicamenorrhea. (https://doi.org/10.1023/A:1026229810876) humans: adaptationandmaladaptation. 327–335. with PRLadenomas. ABCB1 predictsideeffectsoftreatmentwithcabergolineinpatients Stalla GK &Uhr M.Polymorphismsofthedrugtransportergene (https://doi.org/10.1002/syn.21805) disorder viadopamineD3receptors. 168–172. therapy ofParkinson'sdisease. 187–195. . 0727-2) Endocrine prolactinomas withdopamineagonists:alwaysworththegamble? JNEUROSCI.4284-11.2012) DeBesi L &Mastrogiacomo I.Psychosomatic aspectsof ajp.142.2.242) of Psychiatry hyperprolactinemia withbromocriptine. 9378(76)90863-2) 2017 2016 (https://doi.org/10.1176/ajp.141.6.759) (https://doi.org/10.1530/EJE-12-0198) (https://doi.org/10.1016/j.physbeh.2011.04.055) (https://doi.org/10.1530/eje.1.02075) Endocrine Reviews 1976 317 1985 Drug Safety Drug 516–524. 51 125 205–210. 142 859–862. European Journal ofEndocrinology European Journal 2012 European Journal ofEndocrinology European Journal American Journal ofPsychiatry American Journal 242–244. 2018 (https://doi.org/10.1001/jama.2016.19699) American Journal ofObstetricsand American Journal Downloaded fromBioscientifica.com at09/27/202102:03:01AM 2001 32 (https://doi.org/10.1007/s12020-015- 41 7316–7324. Physiology andBehavior (https://doi.org/10.1016/0002- 19–75. 1981 (https://doi.org/10.1176/ 22 724–763. Synapse 36 (https://doi.org/10.1016/ (https://doi.org/10.1007/ Pituitary 122–128. Pituitary American Journal American Journal 180 (https://doi.org/10.1523/ 2015 (https://doi. 2011 :1 2003 , edn4,ch16,pp 69 1984 (https://doi. 96 2012 183–189. 2011 2006 6 273–288. 35–39. 141 167 104 154

et al 38 via freeaccess . European Journal of Endocrinology

33 32 31 30 29 28 27 26 25 24 23 22 21 20 19 18 Clinical Study Bancos I, Nannenga MR,Bostwick JM, Silber MH,Erickson D& De Sousa SM,Chapman IM,Falhammar H&Torpy DJ. Dopa- Vinkers DJ &vanderWee NJ. Acaseofmaniaafterlong-termuse Thondam SK, Alusi S,O'Driscoll K,Gilkes CE,Cuthbertson DJ Falhammar H &Yarker JY. Pathologicalgamblingandhypersexuality Almanzar S, Zapata-Vega MI &Raya JA.- Davie M. Pathologicalgamblingassociatedwithcabergolinetherapy van Holst RJ,denBrink W, Veltman DJ &Goudriaan AE.Why Bastiaens J, Dorfman BJ,Christos PJ&Nirenberg MJ.Prospective Athanasoulia-Kaspar AP, Popp KH&Stalla GK.Neuropsychiatric Moore TJ, Glenmullen J&Mattison DR.Reportsofpathological Celik E, Ozkaya HM,Poyraz BC,Saglam T&Kadioglu P. Impulse Athanasoulia AP, Ising M,Pfister H,Mantzoros CS,Stalla GK Kars M, vanderKlaauw AA,Onstein CS,Pereira AM&Romijn JA. Johnson MD, Woodburn CJ &Vance ML. Qualityoflifeinpatients Rocco A, Mori F, Baldelli R,Aversa A, Munizzi MR,Nardone MR, agonist-treated prolactinomas and nonfunctioning pituitary agonist-treated prolactinomasandnonfunctioning pituitary Nippoldt TB. Impulsecontroldisorders inpatientswithdopamine 618–624. prolactinomas treatedwithdopamine agonists. testotoxicosis: disruptivehypersexuality inhypogonadalmenwith org/10.1016/j.genhosppsych.2007.05.004) of quinagolide. WNF.0b013e31829fc165) Neuropharmacology treatment withbromocriptineforamacroprolactinoma. & Daousi C.Impulsecontroldisorderinapatientonlong-term 190 in cabergoline-treatedprolactinoma. psym.2012.10.002) Psychosomatics induced impulsecontroldisordersinapatientwithprolactinoma. jnp.2007.19.4.473) and ClinicalNeurosciences prolactinoma. in apatientwithpituitary 34 in pathologicalgambling. gamblers failtowin:areviewofcognitiveandneuroimagingfindings mds.25291) Movement Disorders cohort studyofimpulsecontroldisordersinParkinson’s disease. R88–R94. an endocrinologistandapsychiatrist. and metabolicaspectsofdopaminergictherapy:perspectivesfrom 1930–1933. dopamine receptoragonistdrugs. gambling, hypersexuality, andcompulsiveshoppingassociatedwith 2018 Epub. agonist therapy:aprospectivestudywith1yearfollow-up. control disordersinpatientswithprolactinomareceivingdopamine org/10.1159/000335996) controls. adenomapatientsandage-gender-matched pituitary patients withprolactinomas:acomparisonnonfunctioning & Sievers C.Distinctdopaminergicpersonalitypatternsin 133–139. microprolactinoma. Quality oflifeisdecreasedinfemalepatientstreatedfor org/10.1023/B:PITU.0000004798.27230.ed) adenoma. with apituitary org/10.1016/0306-4530(93)90055-P) adenomas. on psychologicalprofileofpatientswithPRL-secretingpituitary Fabbrini A &Falaschi P. Effectofchronicbromocriptinetreatment 257–262. hyperprolactinemia. 87–107. 97. Neuroendocrinology (https://doi.org/10.1530/EJE-07-0259) (https://doi.org/10.1159/000287773) (https://doi.org/10.1007/s12020-016-1088-1) (https://doi.org/10.1530/EC-18-0030) Psychoneuroendocrinology (https://doi.org/10.1016/j.neubiorev.2009.07.007) 2013 General HospitalPsychiatry 2013 2013 European Journal ofEndocrinology European Journal 54 Psychotherapy andPsychosomatics 387–391. 36 2007 28 Neuroscience andBiobehavioralReviews Pituitary 170–172. 2012 327–333. 19 (https://doi.org/10.1016/j. 473–474. 96 JAMA Internal JAMA Internal 2003 1993 204–211. Medical Journal ofAustralia Medical Journal (https://doi.org/10.1097/ A GIoachimescuandothers (https://doi.org/10.1002/ Endocrine Connections 6 2007 18 81–87. Journal of Neuropsychiatry ofNeuropsychiatry Journal (https://doi.org/10.1176/ 57–66. (https://doi. 29 Endocrine (https://doi. 464. (https://doi. 2007 1983 (https://doi. 2014 Clinical 2017 157 Endocrine 2018 40

174

55 2009 2010 7

dopamine agonists Psychological effectsof 50 49 48 47 46 45 44 40 39 38 37 36 35 34 43 42 41 Hoffer ZS, Roth RL&Mathews M.Evidence forthepartialdopamine- Yuksel RN, ElyasKaya Z,Dilbaz N&CingiYirun M. Ali S, Miller KK&Freudenreich O.Managementofpsychosis Turner TH, Cookson JC,Wass JA, Price PA Drury PL, &Besser GM. Mohapatra S &Nayak MR.Cabergoline-inducedmaniainapatient Bilal L &Ching C.Cabergoline-inducedpsychosisinapatient Cabeza GA, Flores LF, Iniguez IE, Calarco ZE &Valencia PF. Acute Freeman B, Levy W&Gorman JM.Successfulmonotherapy Rovera C, Cremaschi L,Thanju A,Fiorentini A,Mauri MC,Serati M, Bakker IC, Schubart CD&Zelissen PM.Successfultreatmentofa Burback L. Managementofamicroprolactinomawitharipiprazole Barake M, Evins AE,Stoeckel L,Pachas GN,Nachtigall LB,Miller KK, Bulwer C, Conn R,Shankar A,Ferrau F, Kapur S,Ederies A, Martinkova J, Trejbalova L, Sasikova M,Benetin J&Valkovic P. Peter SA, Autz A&Jean-Simon ML.Bromocriptine-induced Al-Semaan YM, Clay HA&Meltzer HY. Clozapinein Sheldrick AJ &Grunder G.Aripiprazolereducesserumprolactinina psy.50.4.317) Psychosomatics in patientswithiatrogenicortumorogenic hyperprolactinemia. agonistaripiprazoleasafirst-line treatmentofpsychosis org/10.1177/2045125315626345) Advances inPsychopharmacology Cabergoline-induced manicepisode:casereport. S0033-3182(10)70718-0) literature. associated withaprolactinoma:casereportandreviewofthe org/10.1136/bmj.289.6452.1101) dopamine agonists. tumourswith Psychotic reactionsduringtreatmentofpituitary 2017 microadenoma. of pituitary neuropsych.11110348) Clinical Neurosciences with undiagnoseddepression. prolactinoma. tobromocriptinetreatmentinapatientwith psychosis secondary 700–701. Psychiatry psychotic featuresinbipolarIdisorder:acasereport. Lindenmayer JP &Altamura AC.Cabergolinecaninducemaniawith Diabetes andMetabolismCaseReports prolactinoma withtheantipsychoticdrugaripiprazole. and MetabolismCaseReports in awomanwithcabergoline-inducedmania. s11102-013-0480-6) pilot study. patients ondopamineagonisttherapyforhyperprolactinemia:a Biller BM, Tritos NA &Klibanski A.Investigationofimpulsivityin Endocrinology disorder inanadolescentwithagiantprolactinoma. Korbonits M &Spoudeas HA.Cabergoline-relatedimpulsecontrol 34 adenomas. in patientswithpituitary Impulse controldisordersassociatedwithdopaminergicmedication 863–868. schizophrenia. org/10.1097/00004714-199704000-00016) Clinical Psychopharmacology treatment ofbromocriptine-inducedpsychosis. 2008 woman withprolactinomaandacutepsychosis. (https://doi.org/10.1097/01.pra.0000265771.47153.a0) prolactinoma. treatment witharipiprazoleinapatientschizophreniaand adenomas: acase-controlstudy. 179–181. 39 41 350–351. 160. 2016 (https://doi.org/10.1111/cen.12375) Psychosomatics Pituitary 2017 (https://doi.org/10.1097/WNF.0b013e3182281b2f) (https://doi.org/10.1055/s-2008-1076721) 2009 Revista deInvestigaciónClínica Journal ofPsychiatricPractice Journal Journal oftheNationalMedicalAssociation Journal 22 94–95. (https://doi.org/10.4103/0253-7176.207314) 86 2014 BMJ 50 2012 862–864. 317–324. 1984 2010 17 (https://doi.org/10.1016/j.ajp.2016.05.010) Downloaded fromBioscientifica.com at09/27/202102:03:01AM 24 1997 2015 Indian Journal ofPsychologicalMedicine Indian Journal 150–156. E54. 289 Journal of Neuropsychiatry and ofNeuropsychiatry Journal 51 2016 (https://doi.org/10.1111/cen.13339) Clinical Endocrinology 17 (https://doi.org/10.1176/appi. 370–376. 2015 1101–1103. (https://doi.org/10.1176/appi. 126–128. 2016 https://eje.bioscientifica.com Clinical Neuropharmacology 6 229–231. 150100. (https://doi.org/10.1007/ 2016 2007 180 (https://doi.org/10.1016/ 1984 Endocrinology, Diabetes (https://doi. (https://doi. :1 Journal of Journal 160028. Pharmacopsychiatry 13 (https://doi. Therapeutic 36 120–124. 147–149. Clinical 2014 Asian Journal of Asian Journal Endocrinology, 1993 80 85

2011 39

via freeaccess

European Journal of Endocrinology https://eje.bioscientifica.com

52 51 Clinical Study Santos Andrade EH,Pan PM,daSilva PF&Gadelha A.New Broekhof R, Gosselink MJ,Pijl H&Giltay EJ.Theeffectof insights inthemanagementofantipsychoticstreatment Hospital Psychiatry prolactinomaandchronicpsychosis. symptomatic pituitary aripiprazole andquinagolide,adopamineagonist,inpatientwith 2012 34 209.e1–209.e3. A GIoachimescuandothers General Accepted 25October2018 Revised versionreceived5October2018 Received 15August2018

dopamine agonists Psychological effectsof 53 Liu W, Zahr RS,McCartney S,Cetas JS,Dogan A&Fleseriu M. Pituitary aretrospectivesinglecenterstudy. surgery: who requiredpituitary Clinical outcomesinmalepatientswithlactotrophadenomas review oftheliterature. schizophrenia inapatientwithprolactinoma:casereportand 2018Epub. Case Reports inMedicine Case Reports Downloaded fromBioscientifica.com at09/27/202102:03:01AM 180 2010 :1 2010 573252. 40 via freeaccess