Long-term systemic glucocorticoid therapy: Patients' representations prescribers' perceptions and treatment adherence

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Availableonlineat

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Original article

Long-term systemic glucocorticoid therapy: Patients’ representations, prescribers’ perceptions, and treatment adherence

Kawtar Nassar

^a,∗

, Saadia Janani

^a

, Christian Roux

^b

, Wafae Rachidi

^a

, Nouﬁssa Etaouil

^a

, Ouafaa Mkinsi

^a

aServicederhumatologie,centrehospitalieruniversitaireIbnRochd,facultédemédecineetdepharmacie,Casablanca,Morocco

bServicederhumatologieB,hôpitalCochin,universitéParis-Descartes,Paris,France

a r t i c l e i n f o

Articlehistory:

Accepted15April2013 Availableonline13August2013

Keywords:

Glucocorticoids Treatmentadherence Inﬂammatorydisease Adverseeffects

a b s t r a c t

Introduction:Glucocorticoidshavebeenusedsince1948fortheiranti-inﬂammatoryandstructuraleffects invariousinﬂammatorydiseases.Theoptimaluseofglucocorticoidsremainscontroversial.Patients mayhaveanumberofconcernsabouttheeffectsofglucocorticoids.Manyfactorscanadverselyaffect treatmentadherence.

Objectives:Toevaluatethemainadverseeffectsreportedbypatientsandphysicians,andtoassessrep- resentationsassociatedwithglucocorticoidtherapyandtheunderlyingdisease,viameasurementsof treatmentadherence,withthegoalofoptimizingtreatmentstrategiesandimprovingpatientinforma- tion.

Methods:FromDecember2011toMay2012,weconductedtwosurveysin125patientsreceivinglong- termglucocorticoidtherapyandfollowed-upattherheumatologydepartmentoftheteachinghospital inCasablanca,Morocco,andin85hospitalphysiciansinvariousspecialties,respectively.

Results: Mean glucocorticoid therapyduration was 6years,mean maximalprescribed dosage was 44.87mg/d,and50.4%ofthepatientshadinﬂammatoryjointdisease.Adverseneuropsychiatriceffects werereportedby70outof125(56%)patients.Weightgainwastheadverseeffectdeemedmostboth- ersomebythephysicians,whosigniﬁcantlyunderestimatedtheoccurrenceofneuropsychiatricadverse effects(27%vs56%,P=0.034).Adherencewaspoorin80outof125(64%)patients,and22outof125 (18%)patientsreportedepisodesoftreatmentdiscontinuation.

Conclusion: Prescribersunderestimatethefrequencyofneuropsychiatricadverseeffectsoflong-term systemicglucocorticoidtherapy.Regularfollow-upvisitsduringtreatment,withcollectionofsystemic adverseeffectsmightimprovetreatmentadherence.

1. Introduction

Glucocorticoidstakeprideofplaceinthetreatmentofmany diseases.Theestimatedprevalenceofsystemicglucocorticoidther- apyprescribedfor3monthsormoreis0.2%to0.5%inthegeneral population[1,2]and 1.7%in women olderthan55years ofage [2].Althoughthebeneﬁtsofglucocorticoidtherapyarewellestab- lished,theycomeatthecostoffrequentadverseeffects(AEs)[3,4].

BoththeoccurrenceofAEsand patientconcerns aboutpossible AEscanresultinpoortreatmentadherence.PerceptionsofAEs, particularlyregardingtheirseverityandconsequences,maydiffer betweenpatientsandphysicians.

Weconductedsurveysamongpatientsandspecialistphysicians toidentifytheAEstheydeemedmostimportant.Ourgoalwasto

∗Correspondingauthor.33,avenuedu2Mars,résidenceYoussef,Apparentement 2,étage1,Casablanca,Morocco.

E-mailaddress:nassarkawtar@gmail.com(K.Nassar).

improvepatientinformationand,ultimately,treatmentadherence basedonananalysisofthesurveyresults.

2. Methods 2.1. Studydesign

We conducted two cross-sectional surveysbetween Decem- ber2011 and May 2012.One survey included125consecutive outpatientsorinpatientsattherheumatologydepartmentofthe teachinghospitalinCasablanca,Morocco.Inclusioncriteriawere ageolderthan18yearsandoralglucocorticoidtherapyforatleast 1month ina dailydosageof atleast 5mg.Patients weregiven bolusintravenous injections orintra-articular injectionsof glu- cocorticoidsbeforethecurrentoralglucocorticoidregimenwere eligible.Wedidnotincludepatientsinwhompoorgeneralhealth precludedquestionnairecompletionorwhohadbeentakingoral glucocorticoidtherapyforlessthan1month.Thesecondsurvey included85specialistphysicianswhoworkedattheCasablanca 1297-319X/$–seefrontmatter©2013Sociétéfranc¸aisederhumatologie.PublishedbyElsevierMassonSAS.Allrightsreserved.

doi:10.1016/j.jbspin.2013.07.001

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teaching hospital in Morocco and who volunteered for the study.

2.2. Physiciansurvey

AquestionnairewasdevelopedusingphpESPsurveysoftware (http://sourceforge.net/projects/phpesp/)attheBiostatistics,Epi- demiology,andMedical Informaticsdepartmentofourhospital.

The questionnaire has three sections, each with dichotomous and multiple-choice items. The ﬁrst section collected informa- tionontheidentityandspecialtyofthephysicianandspeciﬁed the number of patientsunder the physician’s care, taken as a marker of experience. The second section obtained details on prescriptionoflong-termsystemicglucocorticoidtherapybythe physician.Finally,thethirdsectioncollectedtheglucocorticoid- relatedAEsdeemedmostbothersomebythephysicians,basedon personalexperience.Thephysiciancompletedthequestionnaire then,handedittotheinvestigatoron-site.

2.3. Patientquestionnaire

An anonymous questionnaire in French comprising both dichotomousandmultiple-choiceitemswascompletedonceby the investigator based on a patient interview. If needed, the investigatortranslatedtheitemsintoArabicandprovidedexpla- nationsabouttheirmeaning.Thefirstsectionofthequestionnaire collectedinformationonsocial status, reasonfor glucocorticoid therapy,glucocorticoidtherapydosageandduration,andsource of informationon AEs.Thesecond sectionevaluated treatment adherencebasedonglucocorticoidtaperingregimens,adherence toadjuvanttreatments(e.g.gastroprotectiveagents,vitaminDand calciumsupplements, potassium supplements,and low sodium diet),adherencetofollow-upvisits,self-medication(definedasuse bythepatientsofglucocorticoidsobtainedwithoutamedicalpre- scription),andfailuretorefilltheprescription.Theinterviewerthen askedthepatienttomarktheAEsheorsheconsideredbothersome onaclosedlistofallpossibleAEs.Severalresponseoptionswere provided.

2.4. Dataanalysis

Theinvestigatorwhoparticipatedinbothsurveysanalyzedthe data.Someoftheresultsaredescribedasmean±SD.Fisher’sexact testwasusedtocomparequalitativevariables.

3. Results

The 85 physicians consisted of 16 (18.8%) rheumatologists, 15dermatologists,12nephrologists,10gastroenterologists,eight interns,eightneurologists,sixpulmonologists,ﬁveinfectiologists, threeoncologists, andtwo pediatricians.Table1 reportsdetails ontheglucocorticoidtreatmentsprescribedbythesephysicians.

Table2showsthemaincharacteristicsofthe125studypatients.

Amongthem,66(53%)patientsadheredtotheadjuvanttreatments, including52whoadheredtovitaminDandcalciumsupplementa- tion,potassiumsupplementation,andgastroprotectivetreatment.

Only14patientsfollowedalowsodiumdiet.Adherencewaspoor in64%ofthepatients(Table3).Episodesoftreatmentdiscontinu- ationwerereportedby22patientsandcontinuousglucocorticoid usewithoutamedicalprescriptionby58patients.

Table4reportstheAEsdeemedmostbothersomeandascribed toglucocorticoidtherapybythepatients,aswellasthemainAEs reportedbythephysiciansbasedontheirpersonalexperience.The patientsunderestimatedthecomplications considered common bythephysicianswhereas thephysicians signiﬁcantlyunderes- timatedtherateofneuropsychiatricAEs.Thus,neuropsychiatric

Table1

Detailsontheglucocorticoidtreatmentsprescribedbythe85surveyedspecialist physicians.

Modalitiesofglucocorticoidtherapy prescribedbytherespondents

Number(%) ofphysicians Prescriptionoforallong-termglucocorticoid

therapyexpectedtolast≥1year

53(62.3)

Prednisone 70(82.3)

Startingdosage≥20mg/d 41(48.2)

Diagnosis

Connectivetissuedisease 34(40)

Inﬂammatoryjointdisease 25(29.5)

Other:cancer,extramembranous

glomerulonephritis,vasculitis,sarcoidosis, inﬂammatorymyositis

29(34)

Table2

Maincharacteristicsofthe125surveyedpatientsreceivinglong-termsystemic glucocorticoidtherapy.

Females 103(82.4%)

Meanageinyears 46.5±10

Socioeconomicstatus

Low 84(67.2%)

Intermediate 28(22.4%)

High 13(10.4%)

Diagnosis

Rheumatoidarthritis 63(50.4%)

Systemiclupuserythematosus 22(17.6%)

Other(sarcoidosis,dermatomyositis, vasculitis,scleroderma,overlapsyndromes)

40(32%)

Prednisone 98(78.4%)

Numberofpatientsonlong-termsystemic glucocorticoidtherapyfor≥1year

89(71.2%)

Meantreatmentdurationinmonths 73.6

Numberofpatientswithaprescribeddosage

≥20mg/dforatleast2monthsatanytime

75(60%) Systemiclupuserythematosusandother

diagnoses

62

Rheumatoidarthritis 13

Meanmaximaldosage 44.9mg/d

Meancurrentdosage 11.4mg/d

(n=62) Informationonthediagnosisandtreatment

effectsbeforetreatmentinitiation

80%

(n=100)

Byphysicians 81(64.8%)

Self-information 19(15.2%)

Noinformation 25(20%)

symptomswerereportedby56%ofthepatientscomparedtoonly 27%ofthephysicians(P=0.034).Theninepatientswithdepres- sionhadnodetectablesymptomsofdepressionatglucocorticoid initiation.Mostofthesepatientshadalowsocioeconomicstatus

Table3

Patient-reportedreasonsfornon-adherenceandself-medication.

Reasonsforpoortreatmentadherenceand self-medication

N^oofpatients, n=80(64%) Intermittenttreatmentdiscontinuation 22

Severeadverseeffects 9

Fearandreluctancetowardglucocorticoids 7

Noinformation 6

Continuousself-medicationwithglucocorticoids obtainedwithoutamedicalprescription

58

Symptomrelief 21

Noinformation 15

Inadequateself-information 12

Follow-upvisitsdeemedtoowidelyspaced 11 Inexpensivedrug/disease-modifyingdrug 6 Easyavailabilityofglucocorticoidsfrompharmacists 5

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Table4

Adverseeffects(AEs)reportedbythepatientsasmostbothersomeineverydaylife andmainAEsreportedbythephysiciansbasedontheirpersonalexperience.

Patients(%) Physicians(%) Pvalue

Weightgain 41.6 63.5 0.001

Cutaneouscomplications (facialerythrosis,stretch marks,easybruising, acne)

28.8 41 0.002

Diabetes 18.4 50.6 0.003

Bloodpressureimbalance 14.4 35.2 <0.0001

Lipodystrophy 0 38.2 <0.0001

Neuropsychiatric symptoms

16.8 7 NS

Irritability 18.4 5.8 NS

Insomnia 7.2 3.5 NS

Depression 6.4 2.3 NS

Drowsiness 1.6 –

Suicideattempt 3.2 –

Headache 1.6 –

Tremor 0.8 –

Persecutorydelusions – 8.2

Anxiety Neuropsychiatric

symptoms

56% 27% 0.03

Asthenia 1.6 4.5 NS

Myopathy 20.8 15.2 NS

Lowerlimbedema 0 12.9 <0.0001

Changeineatinghabits 8.8 10.5 NS

Dyslipidemia 12 0 <0.0001

Osteoporosis 4 32 <0.0001

Fractures 1.6 0 NS

ONA 1.6 18.2 <0.0001

Heartburnorgastricpain 6.4 12 NS

Cataract 1 0 NS

Glaucoma 4 0 NS

Recurrentinfections 2.4 0 NS

Hirsutism 1 0 NS

Excessivesweating 1 18.8 <0.0001

Drynessofthemouth 1 0 NS

Amenorrhea 1 10.5 0.001

NoAE 8.8 0 0.001

NS:non-signiﬁcant.

andtwoofthemattemptedtocommitsuicideduringcriticalsocial situations.Theonly patientwho experiencedpersecutory delu- sionshadnoprevioushistoryofpsychiatricdisease.Allpatients withglucocorticoid-induceddepressionreceivedantidepressants andpsychiatricsupport,aswellastaperingoftheirglucocorticoid dosage.Table5providesdetailsonthepatientswhoexperienced neuropsychiatricsymptoms. Theglucocorticoiddosagewassig- niﬁcantlyhigher in thesepatientsthanin thepatientswithout neuropsychiatricsymptoms.

4. Discussion

We found high rates of glucocorticoid AEs reported by both patients and physicians. The patientsunderestimated the occurrenceofAEs,whereasthephysiciansunderestimatedtheneu- ropsychiatricsymptoms. Our resultsareconsistent withearlier data on the AEs of long-term glucocorticoid therapy. In addi- tion,ourfindingthatphysiciansunderestimatedtheoccurrence ofneuropsychiatricsymptomsisin agreementwithtwo earlier studies [5,6]. Endogenous and exogenous glucocorticoids exert pharmacologicaleffects onthe brainthat alter mood,memory, andsleep–wakecycleregulation[7,8].Theprevalenceofneuropsy- chiatricsymptomshasbeenestimatedat15% [9].Theirclinical presentationvaries widely.Although mostsymptoms are mild, somepatientsexperienceseveremanifestationsthatcanimpair self-sufficiencyandtreatmentadherence.Glucocorticoid-induced symptomsmaybedifficulttodistinguishfromdepressionrelatedto

Table5

Comparisonofpatientswithandwithoutneuropsychiatricsymptoms.

Patientswith neuropsychiatric symptoms n=44(35.2%)

Patientswithout neuropsychiatric symptoms n=81(64.8%)

Pvalue

Sex 39women,5men 64women,17men 0.07

Meanage (years)

43.5 49.5 NS

Socioeconomic status

NS

Low 28 56 NS

Intermediate 12 16 NS

High 4 9 NS

Mean treatment duration (months)

69.2 78 NS

Meanmaximal glucocorticoid dosage

46.4mg/d 43.34mg/d 0.01

Meancurrent dosage

12.5mg/d (n=20)

10.32mg/d (n=42)

0.07 Self-

medication

10 48 0.01

Treatment interruptions

9 13 NS

Good treatment adherence

25 20 0.02

NS:non-signiﬁcant.

havingachronicdisablingdisease.NeuropsychiatricAEsofgluco- corticoidsincludesleepdisturbances,depression,manicepisodes, psychoticepisodes,andconfusion[10,11].Fewstudiessystemat- icallyevaluatedtheAEsoflong-termglucocorticoidtherapy[12].

Casesofglucocorticoid-induceddepressionwithariskofsuicide havebeenreported[10].InastudyconductedinFrance,16%ofthe patientscomparedtoonly5%oftheinternsidentiﬁedneuropsy- chiatricsymptomsasthemostbothersomeAEsofglucocorticoid therapy.Ourstudydesigndidnotallowustoidentifythedeter- minants of glucocorticoid-induced neuropsychiatric symptoms.

However,theglucocorticoiddosagewassigniﬁcantlyhigherinthe subgroupwithneuropsychiatricsymptoms.Ameta-analysisiden- tiﬁedtwocasesofsuicideascribedtoglucocorticoidtherapyand indicatedthattheneuropsychiatricsymptomsresolvedwhenthe dosagewasdecreased[13].

Astudyof 372,696patientsreceivingcarefromBritishgen- eralpractitionersandtreatedwithoralglucocorticoidsidentiﬁed 109casesofsuicideorattemptedsuicideand10,220severeneu- ropsychiatric events. The overall incidence was 22 out of 100 patient-years.Comparedtopatientswiththesamediagnoseswho werenottakingglucocorticoidtherapy,thehazardratioswere6.89 forsuicideorattemptedsuicide,1.83fordepression,4.35formanic episodes,5.14forepisodesofdelirium,confusion,ordisorientation, and1.45forpanicattacks.Theriskofsuicidalbehaviorwashighest amongtheyoungerpatientsandtheriskofdelirium,confusion,dis- orientation,ormaniawashighestintheolderpatients.Thestarting glucocorticoiddosagepredictedtheoccurrenceofneuropsychiatric symptoms.Riskfactors forglucocorticoid-inducedneuropsychi- atricsymptoms includedaprevioushistory of neuropsychiatric disordersandahighglucocorticoiddosage.IntheBostonCollabora- tiveDrugSurveillancestudy,theproportionofpatientswithsevere neuropsychiatricsymptomswas1.3%amongpatientstakingless than40mg/dofprednisoneand18.4%amongthosetakingmore than80mg/d[14].Inadditiontoageandglucocorticoiddosage, femalegenderisassociatedwithglucocorticoid-induceddepres- sion[15].

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Physicians must direct greater attention to glucocorticoid- inducedneuropsychiatricsymptomsinordertoimprovepatient management. Patients may fail to spontaneously report these symptoms,thus,contributing toexplain theunderestimation of theirrateofoccurrencebythephysicians.Inaqualitativestudyof eightpatientswhotookoralglucocorticoidtherapyformorethan 5years,fourpatientsreportedavarietyofneuropsychiatricsymp- tomsandﬁvedidnotinformtheirphysicianswhenthesesymptoms occurred.[10].

Despitethemanywell-documentedAEsoflong-termglucocorticoidtherapy,glucocorticoidsarepotentanti-inﬂammatoryagents thatprovidesymptomreliefandalsoexertstructuraleffectswhen used for short periodsand in daily dosages lower than 10mg.

Asaresult,manypatientsbecomedependentonglucocorticoids, whichareconsequentlyusedoverthelongterm,chieﬂytoalleviate theinﬂammatorysymptoms.Wefoundthatbothpoortreatment adherenceand self-medication withglucocorticoids were common.Themainreasonforself-medicationwasadesiretoobtain relieffromthesymptomsofthediseasethatinitiallyprompted theprescriptionforglucocorticoidtherapy.Treatmentdiscontinu- ationsweredueeithertoAEsdeemedseverebythepatientsorto concernaboutpossibleAEs.Ourresultsareconsistentwithprevi- ousdata:AEscanresultinpoortreatmentadherenceandconstitute themost oftencited reason for patient reluctanceto takeglu- cocorticoids[16–18].Inastudyof80internal-medicinepatients enrolledattheinitiationofsystemicglucocorticoidtherapy,after 3monthsoftreatment,53(66%)patientsreportedthatatleastone AEimpairedorsubstantiallyimpairedtheireverydaylife[3].Onthe otherhand,manypatientsdevelopfunctionaldependencyonglu- cocorticoidtherapy,warrantinglong-termprescriptiontoimprove thesymptoms.

Studiesofrepresentationsofdiseasesandtreatmentsfallinto threecategoriesdependingonwhethertheyfocusonindividual representationsrelatedtothedisease,individualrepresentations relatedtothetreatments,orboth.Studiesofrepresentationsofdis- easeconductedoverthepastdecadehaveprovidedspeciﬁcinsights intothecentralroleforinterpretationsofsymptomsandperceived linksofthesymptomstothedisease,aswellasforthemannerin whichpatientsperceivetheimpactofthediseaseontheirevery- daylife.Patientswhoperceivetheirsymptomsclearlyandascribe themto theinﬂammatorydisease aremore likelyto adhereto prescribedtreatments[19–21].Patientsmayevaluatethesever- ityoftheirsymptoms,andconsequentlyoftheirdisease,basedon theimpactofthesymptomsontheirqualityoflife,whichmayin turn,affecttreatmentadherence:thepatientsdecidewhetherthe severityofthesymptomswarrantsthetreatment.Thismechanism hasbeendemonstratedinpatientswithasthma:failuretoadhere toinhaledglucocorticoidtherapyisusuallyduetotheabsenceof perceivedsymptoms[22].

Regarding representations related to glucocorticoid therapy, patientsnotonlybasetheirdecisionsabouttreatmentadherence ontheirperceivedsymptoms,but alsoevaluatetherisk/benefit ratio.Inacross-sectionalstudyof324patientswithchronicdis- eases,beliefsaboutmedicationsaccountedfor19%oftheexplained varianceintreatmentadherence[9].Thesebeliefsmayaffectthe perception that treatmentis necessary, even in theabsence of symptoms.Otherstudiesfoundthatconcernsaboutmedications adverselyaffectedadherence[9,23,24].Themostcommonlycited concernswerefearofAEs,perceivedinadequatesymptomcontrol, afirmbeliefthatunnecessarytreatmentwasforcedonthepatient, andfearofdevelopingglucocorticoiddependency.Theseconcerns areusuallynotcommunicatedtothephysicianbutcancontribute toa decisiontostopthetreatment.Thelinkbetweenrepresen- tationsandadherenceprobablyalsoinvolvesasyetunidentified variables, andfew data havereported factorsthat mayexplain theobservedinter-individualdifferences.Youngageandafemale

predominanceweremajorcharacteristicsofourpopulation.Fur- thermore,ourpatientswereabletoobtainglucocorticoidseasily from pharmacists without a medical prescription. Most of the patientshadalowsocioeconomicstatus,afeaturethatmaycon- tributetoexplainself-medicationwithglucocorticoids,whichare lessexpensivethandisease-modifyinganti-rheumaticdrugs.

Ourstudyhasseverallimitations.Thepatientswererecruitedat ateachinghospitalrheumatologydepartmentandmaynotreﬂect thepopulationofoutpatientsseenbyprimary-carephysicians,in termsofboththeunderlyingdiagnosesandpracticepatterns.Fur- thermore,theperceivedbeneﬁtsofglucocorticoidtherapy were collectedonlyinthepatientswhoreportedself-medication.Fur- therstudiesareneededtoidentifyrepresentationsotherthanthose associatedwiththediseaseortreatment,suchastheexpectations andfearsofthepatients[25–28].

Disclosureofinterest

Theauthorsdeclarethattheyhavenoconﬂictsofinterestcon- cerningthisarticle.

References

[1]VanStaaTP,LeufkensHG,AbenhaimL,etal.Useoforalcorticosteroidsinthe UnitedKingdom.QJM2000;93:105–11.

[2]WalshLJ,WongCA,PringleM,etal.Useoforalcorticosteroidsinthecommunity andthepreventionofsecondaryosteoporosis:acrosssectionalstudy.BMJ 1996;313:344–6.

[3]FardetL,KassarA,CabaneJ,etal.Corticosteroid-inducedadverseeventsin adults:frequency,screeningandprevention.DrugSaf2007;30:861–81.

[4]GabrielSE,SunkuJ,SalvaraniC,etal.Adverseoutcomesofanti-inﬂammatory therapy among patients with polymyalgia rheumatica. Arthritis Rheum 1997;40:1873–8.

[5]Fardet L, Flahault A, Kettaneh A, et al. Corticosteroid-induced clinical adverseevents:frequency,riskfactorsandpatient’sopinion.BrJDermatol 2007;157:142–8.

[6]KayaniS,ShannonDC.Adversebehavioraleffectsoftreatmentforacuteexacer- bationofasthmainchildren:acomparisonoftwodosesoforalsteroids.Chest 2002;122:624–8.

[7]FryeCA,LaceyEH.TheneurosteroidsDHEAandDHEASmayinﬂuencecognitive performancebyalteringaffectivestate.PhysiolBehav1999;66:85–92.

[8]HolsboerF,GrasserA,FriessE,etal.Steroideffectsoncentralneuronsand implicationsforpsychiatric andneurological disorders.AnnNY AcadSci 1994;746:345–59[Discussion359–61].

[9]HorneR,WeinmanJ.Patient’sbeliefsaboutprescribedmedicinesandtheir roleinadherencetotreatmentinchronicphysicalillness.JPsychosomRes 1999;47:555–67.

[10]ReckartMD,EisendrathSJ.Exogenouscorticosteroideffectsonmoodandcog- nition:casepresentations.IntJPsychosom1990;37:57–61.

[11]IsmailK,WesselyS.Psychiatriccomplicationsofcorticosteroidtherapy.BrJ HospMed1995;53:495–9.

[12]FardetL,BlanchonT,Perdoncini-RouxA,etal.Internalmedicinephysicians’

perceptionoffrequencyandimpactofcorticosteroid-inducedadverseevents.

RevMedInt2009;30:113–8.

[13]GenereauT,CabaneJ.Bénéﬁcesdescorticoïdesdansletraitementdelamaladie deHortonetdelapseudopolyarthriterhizomélique:avantagesetincon- vénients.Uneméta-analyse.RevMedInt1992;13:387–91[InFrench].

[14]Noauthorslisted.Acuteadversereactionstoprednisoneinrelationtodosage.

ClinPharmacolTher1972;13:694–8.

[15]KiralySJ,AncillRJ,DimitrovaG.Therelationshipofendogenouscortisolto psychiatricdisorder:areview.CanJPsychiatry1997;42:415–20.

[16]MorrisonE,CrosbieD,CapellA.Attitudeofrheumatoidarthritispatientsto treatmentwithoralcorticosteroids.Rheumatology2003;42:1247–50.

[17]LambertM,ConusP,EideP,etal.Impactofpresentandpastantipsychoticside effectsonattitudetowardtypicalantipsychotictreatmentandadherence.Eur Psychiatry2004;19:415–22.

[18]SullivanPS,CampsmithML,NakamuraGV,etal.Patientandregimencharac- teristicsassociatedwithself-reportednonadherencetoantiretroviraltherapy.

PLoSONE2007;2:e552.

[19]ByerB, MyersLB. Psychologicalcorrelates ofadherenceto medicationin asthma.PsycholHealthMed2000;5:389–93.

[20]JessopDC,RutterDR.Adherencetoasthmamedications:theroleofillness representations.PsycholHealth2003;18:595–612.

[21]HarrisGS,ShearerAG.Beliefsthatsupportthebehaviourofpeoplewith asthma:aqualitativeinvestigation.JAsthma2001;38:427–34.

[22]OhmR,AaronsonLS.Symptomperceptionandadherencetoasthmacontroller therapy?JNursScholarsh2006;43:701–4.

[23]CharlesC,NinotG,SultanS.Patients’illnessperceptionsandadherencetotreat- mentwithinhaledcorticosteroidsinasthma.RevMalRespir2011;28:626–35 [InFrench].

(5)

[24]TarquinioC,TarquinioMP.L’observancethérapeutique:determinationset modèlesthéoriques.PratPsychol2007;13:1–19[InFrench].

[25]LeherP,FeldemJ,GiardinoN,etal.Psychologicalaspectsofasthma.Psychol 2002;70:691–711.

[26]UlrikCS,BackerV,Soes-PetersenU,etal.Thepatient’sperspective:adherence ornon-adherencetoasthmacontrollertherapy?JAsthma2006;43:967–73.

[27]ChambersCV,MarksonL,DiamondJJ,etal.Healthbeliefsandcompliancewith inhaledcorticosteroidsbyasthmaticpatientsinprimarycarepractices.Respir Med1999;93:88–94.

[28]LewisDA,SmitRE.Steroidinducedpsychiatricsyndromes.Areportof14cases andareviewoftheliterature.JAffectDisord1983;5:319–32.