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Psychopharmacological treatment before suicide attempt among patients admitted to a Psychiatric Intensive Care Unit

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Psychopharmacological treatment before suicide attempt among patients admitted to a Psychiatric Intensive Care Unit
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  ELSEVIER RE ~ I   N   2 9 \ H r Journal of AffectiveDisorders II3  2009) 37-44 Researchreport  ourn l of  ffective  isorders www.elsevier.comlIocateljad PsychopharmacologicaltreatmentbeforesuicideattemptamongpatientsadmittedtoaPsychiatricIntensiveCareUnit MicheleRaja a,*, Antonel1aAzzoni a, AlexiaE.Koukopoulos b •ServizioPsichiatricodiDiagnosieCura Ospeda/eSantoSpiritoinSassia Rome Italy b DipartimentodiPsichiatria Ospedale S. Andrea Roma.UniversitddegliStudi   Roma Sapienza   Italy Received27February2008;received in revisedfonn27April2008;accepted 28 April2008Availableonline9June2008 Abstract Background: It isdifficulttoassesstheeffectiveness of treatments in loweringsuicideincidence. Methods: To ascertaintheimpact of antidepressants  AD) onsuicidalbehavior,wecomparedthepsychopharmacologicaltreatmenttakenintheprevious3monthsbycaseswhohadmadeornotasuicideattempt SA)justbeforetheiradmissiontoahospital. Results: In comparisonwithnotSAcases,SAcasesweremorelikelytohavereceived AD andbenzodiazepines BZD)beforehospitalization.Onthecontrary,theywerelesslikelytohavereceivedantipsychotics,antiepilepticmood stabilizers, and lithium. Similarresultswereobservedwhentheanalysiswasrestricted to caseswithadiagnosis of MajorDepression,BipolarDepressionorBipolarMixedstate,ScbizoaffectiveDisorder,DepressiveorMixedtype.Previous AD treatmentseemed to benotrelatedtotheseverity of psychopathologyingeneralortotheseverity of depressiveandanxietysymptoms. Conclusions: Theresultssuggestthattheuse of AD inpatientswithmooddisordersisnotassociatedwithareduction of SArate.Rather,itisnotpossible to excludethat AD orBZDcaninduce,worsen,orprecipitatesuicidalbehaviorinsomepatients,especiallyinthoseaffectedbymooddisorderswithDepressiveorMixedfeatures.Theresultsmustbeconsideredpreliminarysincethisisanopen,non-randomized,non-controlledstudythatwascarriedoutatasinglefacility.© 2008 Elsevier B.V. Allrightsreserved.  eywords Antidepressants;BipolarDisorder;MajorDepression;Suicide;Treatment 1. Introduction Suicideisaleading cause of death in the generalpopulation. Since suicideisa complexbehavior related notonly to clinical but also to socialfactors and systems of care, it is difficult to assess the effectiveness of treat ments in lowering suicideincidence. Wemust recognize   Correspondingauthor.ViaPrisciano26,00136,Rome,Italy.Tel.:+393473422158; fax: +39065898721. E-mail addresses:michele.raja@libero.it.michele.raja@fastwebnet.it  M Raja).0165-0327/ -seefrontmatter @ 2008ElsevierB.V.Allrightsreserved.doi:10.1016/j.jad2008.04.024 that not enough is knownabout suicidal behavior tojustify dogmaticconclusions. In the research on suicide, Randomized ControlledTrials  RCT presentstrongbiases,includingthe following:1)patients who areverysevere,psychoticallydepressed, withcomorbid substance abuse or anxietydisorder, or withknown suiciderisk, are generally ex cluded  Zetin and Hoepner,2007); 2 the settingischaracterized by unusually intensive procedures of assessment and treatment; 3) patients and researchersare highly motivated; 4 arelatively low number of patients enterthe studies and the follow up isshort;  38 MRajaet  l / Journal of AffectiveDisorders   2009 7 44 therefore,theincidence of suicidalbehaviorisrare;evenpooling of datafromsevernlhundredRCTmaynothavesufficientpowertodetectclinicallyimportantrisks or benefits;5)mostRCTarefundedbyphannaceuticalcompanies.Alargemeta-analysis(Gunnelletal.,2005) of 477RCT of SelectiveSerotoninReuptakeInhibitors(SSRls)comparedwithplaceboinover40,000adultssubmitted by phannaceuticalcompaniestothesafetyreview of theMedicinesandHealthcareproductsRegulatoryAgencycouldnotruleoutincreasedrisk of suicideandself-hanncausedbySSRls.Theauthorsconcludedthat,because of thelowincidence of suicide,itwasnotpossibletoruleouteitherathreefoldincrease or adecreaseinitsoccurrenceamongpeopletreatedwithSSRls.Accordingtotheseauthors,abouttwomillions of patientsshouldberandomizedtodetectanimportanteffectonrisk.Ontheotherhand, realworld studiesarecharacterized by methodologicalshortcomings. To minimizetheintrinsiclimitations of natumlisticstudies,someprecautionsarewarranted:1)thedatashouldbecollectedblindtotheir future use;2)selection of casesshould be controlled or avoidedatall;3)onlyhighlyreliabledatashould be examined;4)statisticalanalysisshould be cautiousandconservative;5)testing of hypothesisshouldbebasedondifferentandindependentevidences;6)alternativehypothesesshouldbeimplausible;7)cliniciansinvolvedintheresearchshould be expertandhonest;8)sponsorshipshould be avoided.  n ordertoascertaintheimpact of antidepressanttreatmentonsuicidalbehavior, we designedthepresentobservationalstudywhosemainaimswere:1)toevaluatetheCaseswhohadmadeaSAimmediatelybeforetheiradmission(SACASES)toaPsychiatricIntensiveCareUnit(PICU); 2) toascertainwhichpsychopharmacologicaltreatment  if any)theyhadbeenassuminginthe3monthsbeforeadmission;3)tocomparesuchtreatmentwiththetreatmenttakeninthe3months TableISocio-demographic and clinicalcharacteristics of SA and notSAcases beforeadmission by CasesadmittedtothePICUnotafteraSA(NOTSACASES)inthesameperiod of time.  Method ThestudyinvolvedpatientsadmittedtoaPICU of ageneralhospitalprovidingassistancetoanurbancatchmentarea of 210,000inhabitants.AccordingtotheItalianlaw,mostvoluntarypatientsandallinvoluntarypatientswhoresideinthisareaandwhoneedimmediatepsychiatrichospitalizationareadmittedtothisPICD.Somecases,whoareaffected by mildersymptomsandcandelayimmediatehospitalization,aresometimesadmitted to privateclinics.Thisofferstheuniqueopportunitytoobservemost  if notall)cases of seriousSAinanunselectedsample of patients.Withthepossibleexception of fewcases of SAchamcterizedbyminimalmedicalconsequencesandforwhomimmediatehospitalizationwas not warranted,itislegitimatetoassumethatallSAmadeintheconsideredperiodbyresidentsinthecatchmentareaandmanaged by healthservicesenteredthepresentstudy.AdmissionstothePICUexcludepersonsunderage18.Thepatientsexaminedwereallthosedischargedbetween1April2004 and   March2007.Thefollowingdatawereascertainedforeachpatient:sex,age,diagnosis(DSM-IV-TR),type of admission(voluntary or involuntary),length of hospitalization,aggressive or violentbehavior(Morrison,1992),psychopharmacologicaltreatmentinthe3monthsprecedingadmissionandinthecourse of hospitalization,andClinicalGlobalImpression(CGI). We definedSAasapotentiallyselfinjuriousactionwithanon-fataloutcomeforwhichthereisevidence,eitherexplicit or implicit,thattheindividualintendedto k ll himself7herself.Theaction mayor maynotresultininjuries(Moscicki,1997).Previouspsychophannacologicaltreatmentwasassessed by askingpatients,theirrelatives,andtheirtreatingpsychiatrists,andbyexaminingmedicalcharts.   the Age(Years)(±SD)44.9(±15.8)42.1(±14.6)2.055Hospitalizationdays9.9(±11.7)lOA(±11.7)0.462Gender(M/F)Parents(YINIU)Commitment(YIN)PreviousSA(YINIU)SAcases 59 45.7 )nO 54.3 ) 5 (39.5 )/72(55.8 )/6(4.7 )23(17.8 )/106(82.2 )48(37.2 )/49(38.0 Y32(24.8 )Not SA cases647(52.5 )/586(47.5 ) 362  29A )n82 (63.4 )/89  72 ) 258 20.9 )1975 79.1 ) 213(17.3 )/451(36.6 )/569(46.1 )1.8626.1690.50710.620 fd P 1 .1722.046* 1 .4762.001* fd P 1353.040*1360.644 MJF   MaleslFemales; Y/NIU   YeslNolUnavaiIable-Unreliable; SA   SuicideAttempt;*   statisticallysignificant.    Raja el al / Journal   AffeetiveDisorders /13  2009 7 44 39 Table2Diagnoses inSAand notSA cases Diagnosis SAcases NotSA cases t- fd P Schizophrenia1 (0.8 )59 (4.8 ) 3.558 1.059SchizoaffectiveDisorder(all)7 (5.4 )210 (17.3 )10.8921.000*SchizoaffectiveDisordermanic 0(0 ) 119 (9.7 ) 12.4591.000*SchizoaffectiveDisorderDepressive4(3.1 ) 26(2.1 )0.172 1 .678 SchizoaffectiveDisorder Mixed 3 (23 ) 65 (5.3 ) 1.5611 .212Unipolar Depression 20 (15.5 ) 26 (2.1 )60.1731.000* Bipolar Disorder(all) 85(65.9 ) 738(59.9 )1.5371.215 Mania 2(1.6 ) 361(29.3 ) 44.522 1.000* Bipolar Depression 27(20.9 ) 80 (6.5 )31.682 1.000* BipolarMixed55 (42.6 )292(23.7 ) 21.109 1.000*Bipolar NOS 1(0.8 )5(0.4 ) 0.009 1.924Psychosis NOS 4(3.1 )92(7.5 ) 2.757 1.097AtypicalDepression7 (5.4 ) 15 (1.2 ) 10.5091.001* Other 5(3.9 )93(7.5 ) 1.834 1.176 SA = SuicideAttempt; * = statisticallysignificant; NOS = Not OtherwiseSpecified. patientwastakingadrugatthetime of admission,aminimwn of 3days of asswnptionswasrequiredtoconsiderthepatient on treabnentwiththatdrug.   thepatienthadsuspendedadrug in thepreviousmonth,aminimwn of15 daysoftreabnentwas required toconsiderthepatient  on treabnent withthatdrug.   asmany Table3 Clinical assessmentsin SAand not SA CASESwithadiagnosis of UnipolarDepression, Bipolar Depression or Bipolar Mixed state,Schizoaffective Disorder Depressive or Mixedtype Number of cases SA CASES NotSA CASES I-test fd P 109489 Age (Years)(:l:SD) 45.4  I 15.8) (l09] 42.6(:1:15.1)[489]1.736 596 .083Hospitalization days 10.2(:1:12.0)[109]10.9(:1:(10.9)[489] 0.595596 .552 GAF (current)15.6(:1:4.7)26.5(:1:8.0)[453] -13.310 554 .000* GAF Oast year best) 56.7  I 10.8)52.2  I 11.9)[368] 3.047 442.002* BPRS57.6  I 11.3)[71]61.4(:1:13.5)[263] -2.174 332 .030* BPRS Anx-Dep. 13.6(:1:2.9)[71]11.9(:1:3.5)[264] 3.844 333.000* BPRSThought Dis. 7.4 (:1:3.6)[71]10.3(:1:4.7)[264] -4.788 333 .000* BPRS Host-agit 5.5(:1:2.8)[71]7.6(:1:3.4)[263] -4.803 332 .000* BPRSExcitement6.8 (:1:2.8)[71]7.7(:1:3.7)[264] -1.866 333.063 BPRS Retirement 6.4 (:1:3.9)[71]7.2(:1:3.9)[264] -1.462 333.145SAPS14.8(:1:13.4)[71]29.5(:1:22.2)[263] -5.320 332 .000* SANS 33.1(:1:22.7)[71]43.7(:1:23.4)[263] -3.470 332 .000* MMSE27.4 (:1:2.6)[66]27.3(:1:2.7)[250] 0.215 314 .830 t- fd p Gender  M/F 49 (45.0 )160(55.0 )215(44.0 /0)/274 (56.0 )0.007 1.935Parents(YIN/U) 46 (42.2 )/60(55.0 )13 (2.8 ) 189(38.6 )/281(57.5 )119(3.9 ) 0.689 2.709 Commitment (YIN)19(17.4 )/90(82.6 ) 56 (11.5 )1433(88.5 ) 2.386 1.122Previous SA (YIN/U) 43 (39.5 )/41(37.6 )/25(22.9 )129(26.4 )1195(39.9 )1165(33.7 )8.6852.013* CGI score:42(1.8 )12(2.5 ) CGI score:5 26 (23.9 ) 92(18.8 ) CGI score:6 79 (72.5 ) 376 (76.9 ) CGI score:72 (1.8 ) 9(1.8 )8.0963.057 Number of comparedcases in squarebrackets; M = Males/Females; Y U = YeslNolUnavailahle-Unreliable; SA = SuicideAttempt; * = statistically significant Anx-Dep. = Anxiety-Depression;BPRS = Brief PsychiatricRatingScale; CGI = ClinicalGlobalImpression; GAF = GlobalAssessment of FunctioningScale; Host-agit. = Hostility-agitation; MMSE = MiniMentalStateExamination; SANS = ScalefortheAssessment of Negative Symptoms;SAPS = Scale for theAssessment of PositiveSymptoms; Thought Dis. = Thought Disorder.  40 M.Rajaetal. / Journal   AffectiveDisorders 113  2009) 37 44 patientsaspossible, on admission, we assessedclinicalconditions by theBriefPsychiatricRatingScale(BPRS),including 24 items,theScalefortheAssessment of PositiveSymptoms(SAPS),theScalefortheAssessment of NegativeSymptoms(SANS),the Mini MentalStateExamination(MMSE),theGlobalAssessment of FunctioningScale(GAF). For purposes of dataanalysis, we combinedtheBPRSitemsintofivesummaryscores: 1 Psychoticcluster whichincludes Conceptualdisorganization,Grandiosity,Hallucinatorybehavior, and Unusualthoughtcontent; 2) Withdrawal-Retardationcluster whichincludes Motorretardation,Emotionalwithdrawal, and Bluntedaffect; 3) Hostility-Suspiciousnesscluster whichincludes Hostility,Suspiciousness, and Uncooperativeness; 4) Anxiety-Depressioncluster whichincludes Anxiety,Depression, and Guilt; 5) GrandiosityExcitementcluster whichincludes ElevatedMood,Grandiosity,Excitement, and MotorHyperactivity. Theduration of thetimeframeforassessmentwas 7 daysfortheBPRS,SAPSandSANS.Clinicalevaluationsweremade by seniorpsychiatrists (MR.   withover 20- years of professionalexperience.Finallongitudinalbestestimateassessmentwasgenerated by authors consensus.The X 2 testwasusedtoanalyzecategoricalvariables. t- testwasperformedforcontinuousvariables.All p valuesweretwotailed,andstatisticalsignificancewassetat p<0.05. 3.Results 3.1.Entiresample In theconsideredperiod,SACASESwere 129(9.5 ), while NOTSA CASESwere 1233(90.5 ). Thedifferencesbetweenthetwogroups are showninTables 1 and 2. Inthe 3 monthsprecedinghospitalization,incomparisonwith NOT SACASES, SA CASESweremorelikely to havereceived AD [50/129(38.8 ) vs 191/1233(15.5 ); cr=41.834; fd= 1; p=.OOO ] andBenzodiazepines(BZD) [56/129(43.4 ) vs 289/1233  23.4 ); x2=23.584;fd= l;p= .000)]. On thecontrary,theywerelesslikely to havereceivedantipsychotics [42/129(32.5 ) vs 622/1233(50.4 );  x2=14.249; fd= 1; p=.OOO ] antiepilepticmoodstabilizers [29/129(22.5 ) vs 431/1233(34.9 );  x2=7.577; fd=l; p=.006)], and lithium [3/129(2.3 ) vs 191/1233  10.5 );  x2=7.929;fd= 1; p=.005)]. Table4Clinicalassessments in SACASESwithadiagnosis of UnipolarDepression,BipolarDepression or BipolarMixedstate,SchizoaffectiveDisorderDepressiveorMixed type whohadbeentreatedwithantidepressants in the3monthsprecedinghospitalization(SAADCASES)or not (SAnotADCASES)Number of casesSAADcases SANotAD cases t-test fd P 4564GAF(cunent)16.3(±4.4)[43]15.0(±4.9)[60]1.396 1 1 .166GAF(lastyearbest)57.2(±10.9)[30]56.4(±10.9)[46]0.30874.759BPRS58.2(±12.1)[31]57.3(±10.9)[41]0.32870.744BPRS Anx-Dep. 14.3(±2.2)[31]13.1(±3.3)[41]1.74470.086BPRSThoughtDis.6.8(±3.3)[31]7.9(±3.8)[41] -1.319 70.192BPRS Host-agit 5.8(±3.3)[31]5.5(±2.3)[41]0.41870.678BPRSExcitement6.9(±2.4)[31]6.8(±3.1)[41]0.19170.849BPRSRetirement6.2(±3.8)[31]6.5(±4.0)[41] -0.329 70.743SAPS12.3  ±i2.0) [31J17.3(±14.3)[41] -1.582 70.118SANS33.2(±22.7)[31]32.7(±22.7)[41]0.08370.934MMSE27.6(±2.6)[28]27.2(±2.6)[38]0.55164.584 t fd   CGlscore:41(2.2 )1(1.6 )COlscore:510(22.2 ) 16 (25.0 )CGIscore:6 34 (75.6 )45(70.3 )CGIscore:7 0 0 ) 2(3.1 )1.6553.886Number of comparedcasesinsquarebrackets.SA = SuicideAttempt;Anx-Dep. = Anxiety-Depression;BPRS = Brief PsychiatricRatingScale; COl = ClinicalGlobalImpression;GAF = GlobalAssessment of FunctioningScale; Host-agit = Hostility-agitation;MMSE = MiniMentalStateExamination;SANS = ScalefortheAssessment of NegativeSymptoms;SAPS = ScalefortheAssessment of PositiveSymptoms;ThoughtDis. = ThoughtDisorder.  = statisticallysignificant.  M. Rajaetal. / Journal of AffectiveDisorders 113  2009)37-44 41 Thirty-eight SA CASES 29.5 )and377NOTSACASES 30.6 )didnottakeanypsychophannacologicaltreatment in the3monthsprecedinghospitalization.Thedifference is notsignificant  :i=2.642;fd=2;p=.267 . 3.2.ComparisonbetweenSAand NOT SACASESwithamooddiagnosis To comparemorehomogeneousgroupsandtofocustheanalysisonthecasesmorerelevantwithrespecttothe aims of thestudy,weconsideredonlycaseswithadiagnosis of MajorDepression,BipolarDepression BipolardisordertypeIor   orBipolarMixedstate,SchizoaffectiveDisorder,DepressiveorMixedtype.Fivehundredninety-eightcasesmetcriteriaforthesediagnoses.Amongthem, SA CASESwere109 18.2 ),andNOTSACASES489 81.8 ).Thedifferencesbetweenthetwogroupsareshown in Table3. In comparisonwithNOT SA CASES,SACASESweremorelikelytoreceiveadiagnosis of UnipolarDepression,BipolarDepression,orDepressiveSchizoaffectiveDisorder[51/109 46.8 )vs132/489 27.0 );   7.415, DF=I; p=.006] andreceivedhigherscores of BPRS Anxiety-Depressioncluster  Table3),reflectingmoreseveresymptoms of depressionoranxiety.NOTSACASESreceivedworsescoresonmost of thescales,withtheexception of currentGAF whereSACASESreceivedaworsescoredeterminedbytheirSA)andBPRS Anxiety-Depressioncluster  whereSACASESreceivedhigherscoresreflectingmoreseveresymptoms of depressionoranxiety). In the3monthsprecedinghospitalization, in comparisonwithNOTSACASES,SACASESweremorelikelytohavereceivedAD[45/109 41.3 )vs122/489 24.9 );  X 2   11.019; fd= 1; p=.OOO ] andBZD[49/109 44.9 )vs143/489  29.2 );  r=9.385;fd= l;p=.002)]. Onthecontrary,theywerelesslikelytohavereceivedantipsychotics[38/109 34.9 )vs269/489 55.0 );  X 2 = 13.688; fd = 1; P =.000)],antiepilepticmoodstabilizers[28/109 25.7 )vs205/489 41.9 );  r=9.207; fd= 1; p= .002)],andlithium[3/109 2.7 )vs64/489 13.1 );  X 2 =8.560;fd= 1; p=0.003)]. 3.3.ComparisonbetweenSACASESwithadiagnosis of BipolarandUnipolarDepression EightcaseswithUnipolarDepression 40 )and 13 withBipolarDepression 47 )hadbeentreatedwith Table5Clinicalassessmentsinnot SA CASESwithadiagnosis of UnipolarDepression,BipolarDepression or BipolarMixedstate,SchizoaffectiveDisorderDepressive or Mixedtypewhohadbeentreatedwithantidepressants in the3monthsprecedinghospitalization notSAADCASES) or not not SA not AD CASES)Number of casesNotSA AD cases NotSA Not AD cases t-test fd P 122367GAF current)28.2  :1:9.0 [116]25.9  :1:7.5 [337]2.712451.007*GAF lastyearbest)54.8  :1:11.1 [93]51.3  :1:12.0 [275]2.462360 .014· BPRS58.5  :I: 14.4)[73]62.5  :I: 12.9)[190]  2.163 261.031*BPRS Anx Dep. 12.5  :1:3.6 [73]11.7  :1:3.4 [191]1.710262.088BPRSThoughtDis.8.4  :1:4.1 [73)11.0  :1:4.7 [191]  4.173 262.000*BPRS Host agit 6.8  :1:3.2 [73]8.0  :1:3.4 [190]  2.444 261.015*BPRSExcitement7.0  :1:3.2 [73]7.9  :1:3.8 [191]  1.937 262.054BPRSRetirement7.5  :1:4.0 [73] 7.1  :1:3.9 [191]0.756262.450SAPS20.5  :1:18.1 [73]33.0  :1:22.6 [190]  4.198 261.000*SANS44.4  :1:24.3 [73]43.4  :1:23.0 [190]0.308261.759MMSE27.1  :1:3.1 [69]27.4  :1:2.6 [181]  0.756 248.451 t- fd   CGIscore:457CGIscore:5 3161 CGIscore:686290CGIscore:7099.403.031*Number of comparedcasesinsquarebrackets.SA = SuicideAttempt; Anx Dep. = Anxiety-Depression;BPRS = Brief PsychiatricRatingScale;CGI = ClinicalGlobalImpression; GAF = GlobalAssessment of FunctioningScale; Host agit = Hostility-agitation;MMSE = MiniMentalStateExamination;SANS = ScalefortheAssessment of NegativeSymptoms;SAPS   ScalefortheAssessment of PositiveSymptoms;ThoughtDis.   ThoughtDisorder.   statisticallysignificant
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