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A naturalistic study of suicidal adolescents treated with an SSRI: suicidal ideation and behavior during 3-month post-hospitalization period

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Describe suicidal ideation and suicide related/other emergencies (SRE), among depressed and acutely suicidal adolescents during a 3-month period following psychiatric hospitalization. One hundred twenty adolescents, who were both depressed and
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  A   naturalistic   study   ofsuicidaladolescents   treated   with   an   SSRI:Suicidal   ideation   andbehavior   during   3-monthpost-hospitalizationperiod § NeeraGhaziuddin a, *,ChristopherMerchant b,1 ,   RichardDopp a ,CherylKing a a University   of    Michigan,    Ann    Arbor,   United   States b Northeastern   Illinois   University,   Chicago,   United   States 1.   Introduction The   overall   aimofthe   present   study   was   to   describe   suicidalideation   and   suicide-related   and   other   emergencies   during   a   3-month   post-hospitalization   period   among   depressed   and   suicidaladolescents   who   were   receiving   SSRIs.   A   secondary   aim   ofthestudy   was   to   describe   variability   inoutcome   among   subgroups   of participants   receiving   SSRIs   alone   or   in   combination   withantipsychotic   and/or   an   anti-epileptic   mood   stabilizer   medication.Theclinical   significance   ofthis   study   is   considerable   becausesuicidal   thoughts   and/or   behaviors   are   common   amongdepressed   adolescents   (Cash   and   Bridge,   2009),and   treatmentofthese   adolescents   has   become   increasingly   challenging   duetoconcerns   of    increased   suicidal   ideation   and/or   behavior   inassociation   with   SSRIs.   Published   literature   to   date   hasaddressed   several   important   questions   related   to   theassociation   between   suicidal   ideation   and/or   behaviors   and   SSRIs.However,   few   studies   have   examined   associations   betweenSSRIs   and   suicidal   thoughts   and   behaviors   among   adolescentswhoare   already   suicidal.   Furthermore,   there   is   scantinformation   regarding   these   outcomes   when   SSRIs   are   concur-rentlyprescribed   with   antipsychotics   and/or   anti-epilepticmoodstabilizers   to   depressed   and   simultaneously   suicidaladolescents. Asian    Journal   ofPsychiatry   xxx   (2014)   xxx–xxx A   R    T   I   C   LE   I   N   F   O  Articlehistory: Received   11   November   2013 Receivedinrevisedform22March2014 Accepted   31   March   2014 Availableonlinexxx Keywords: AdolescentsSuicideSSRI A   BS   T   RA   C   T Objective: Describe   suicidalideationandsuiciderelated/otheremergencies   (SRE),amongdepressedandacutelysuicidaladolescentsduringa3-monthperiodfollowingpsychiatrichospitalization. Methods: Onehundred   twentyadolescents,whowereboth   depressedand   suicidal,   were   receivinganSSRIeitheralone   orin   combinationwithothermedications,remainedonaconsistent   medicationregimenbetweenbaselineandat3-monthsandtheir3-monthoutcomedatawereavailable.Theparticipantswere   dividedinto   fourmedicationgroups:SSRIantidepressant   only   ( n =71);SSRI   plusmoodstabilizer   ( n   =   17);SSRIplusantipsychotic( n   =20);andSSRIplus   antipsychoticandmoodstabilizer( n =   12).   Standardizedinstrumentswereused. Results: Meanage=   15.5    1.3,   Caucasian=   80.8%,female=   74.2%,   meanCDRS-R    =   61.7  12.1,   suicideattempt   duringmonth   prior   tohospitalization   =   58.6%.   During   the   3-month   post-hospitalization   period:   (1)there   wereno   suicides,sixparticipants   (5%)attempted   suicide   and   21   (17.5%)experienced   anSRE;   (2)declinein   suicidalideation   anddepressionseveritywasnoted;   (3)   SSRI   plus   anantipsychoticgroupreported   thehighest   number   of    SREs;   (4)higher   baselinehopelessness   andaggression   scoreswereassociatedwith   greaterreduction   in   suicidal   ideation   at   3-months. Conclusion: Declinesinsuicidalideation,depressionseverity,and   suicide   attemptswere   noted,irrespectiveofpsychotropic-combinationreceived.A   higherrateof    SREswasassociatedwith   receivinganantipsychoticagentincombinationwithanSSRI.Givennaturalisticdesignofstudy,cause-effectconclusionscannotbedrawn.Thelackofan   objectivemeasureto   identifymedicationadherenceisastudylimitation.    2014ElsevierB.V.All   rightsreserved. § The   study   was   supported   by   theGrant   NIMH   R01   MH63881   andK24MH077705.* Corresponding   author.   Tel.:   +1   734   764   7562;   fax:   +1   734   936   8907. E-mail   addresses:   neerag@med.umich.edu   (N.   Ghaziuddin),C-Merchant@neiu.edu   (C.Merchant),   dopp@med.umich.edu   (R.   Dopp),kingca@umich.edu   (C.King). 1 He   was   adoctoral   student   at   the   University   ofMichigan   when   this   study   wasconducted. G   Model AJP-582;   No.   of    Pages   7 Please   cite   this   article   in   press   as:   Ghaziuddin,   N.,   et   al.,   Anaturalistic   study   of    suicidal   adolescents   treated   with   an   SSRI:   Suicidalideation   and   behavior   during   3-month   post-hospitalization   period.   Asian    J.Psychiatry   (2014),   http://dx.doi.org/10.1016/ j.ajp.2014.03.014 Contents   lists   available   at   ScienceDirect AsianJournalof    Psychiatry jou   rn   al   h   om   epage:   ww   w.els   evier.co   m/locate/ajp http://dx.doi.org/10.1016/j.ajp.2014.03.0141876-2018/    2014   Elsevier   B.V.   All   rights   reserved.  Suicidality   (completed   suicide,   suicide   attempt,   preparationtoward   imminent   suicidal   behavior,   suicide   ideation)   is   aproblemintimately   associated   with   adolescent   depression   and   is   aleadingcause   of    death   in   this   age   group,   ranked   third   in   the   United   Statesbehind   accidents   and   malignancies   (Gibbons   et   al.,   2006).Treatment   of    adolescent   depression   has   beencomplicated   by   aconcern   raised   in   2003   regarding   a   possible   association   betweensuicidality   and   SSRIs,   which   was   followed   by   ablack-box   warningissued   in   2004   by   the   Food   and   DrugAdministration   (FDA).Thewarning   states   that   ‘‘antidepressants   increased   the   risk   forsuicidal   thinking   and   behavior   in   children,   adolescents,   andyoung   adults   in   short-term   studies   of    major   depressive   disorder’’(http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm09273.htm).   This   regulatory   decision   by   the   FDA   was   based   onameta-analysis   of    24trials   involving   over   4500   patients,which   found   agreater   risk   ofsuicidality   (risk   ratio   =   1.95;   95%CI=   1.28–2.98)   during   the   first   few   months   of    initiating   antide-pressant   treatment   (Hammad   et   al.,   2006).A   summary   of    relevant   publications   related   to   this   suspectedassociation   between   antidepressants   and   suicidality   is   as   follows:children   and   adolescents   treated   with   an   SSRI   may   experience   amodest   increase   in   suicidal   ideation   and   behaviors   –   noted   in   ameta-analysis   of    24   trials   (the   majority   sponsored   by   pharmaceu-ticalcompanies   with   the   exception   of    the   TADS   multicenter   trial)(Hammad   et   al.,   2006).However,   another   meta-analysis   of    27   trialsinvolving   adolescents   with   MDD,   non-OCD   anxiety   or   OCD(trialsconducted   between   1988   and   2006),   found   only   a   non-significantincreased   risk   in   suicidal   ideation   and   behaviors   among   those   whohad   received   an   SSRI   compared   with   placebo,   irrespective   of diagnosis   (Bridge   et   al.,   2007).   A   case-control   study   of    medicaidrecipients   who   were   depressed,   found   that   children   and   adoles-cents   receiving   an   SSRI,   but   notadults,   are   more   likely   to   attemptsuicide   (OR    1.52;   95%   CI)   or   die   by   suicide   (OR    15.62;   95%CI).Several   explanations   havebeen   offered   about   thisassociation.   Oneof    these   was   the   result   of    a   re-analysis   of    randomized   controlledstudies   of    fluoxetine   in   youth,   which   found   that   althoughdepressive   symptoms   improved   following   fluoxetine,   suicidalthoughts   or   behaviors   did   notimprove   in   thisage   group   (Gibbonset   al.,   2007,   2012;   Nemeroff    et   al.,   2007;   Valluri   et   al.,   2010;   Valucket   al.,   2004).Another   study   suggested   that   adolescents   who   engage   insuicidal   behaviors   had,   in   fact,   not   received   adequate   treatmentwith   antidepressants   (Dudley   et   al.,   2010).Along   similar   lines,   oneother   study   found   that   pre-treatment   patient   characteristicslargelyaccounted   for   increased   suicidality   (Kubaet   al.,   2011),while   others   have   stated   that   the   studies   which   formed   the   basis   of the   FDA   regulatory   decision   were   limited   due   to   the   exclusion   of suicidal   adolescents   in   clinical   trials   (Antonuccio,   2008;    Jureidiniand   McHenry,   2009)Inaddition   to   the   concern   regarding   the   safety   of    antidepres-sants,   the   FDA   recently   introduced   a   warning   regarding   anincreased   risk   of    suicidal   thoughts   and   behaviors   associated   withseveral   anti-epileptic   drugs   (AEDs).   Thisrisk   involving   AEDs   ispertinent   to   psychiatrists   because   these   agents   are   often   pre-scribed   as   mood   stabilizers.   Although,   thiswarning   does   notspecifically   involve   adolescents,   it   adds   to   the   concern   due   to   theoverall   higher   risk   of    suicidality   among   adolescents.   The   FDA’swarning   regarding   AEDs   was   based   on   a   review   of199trialsinvolving   eleven   different   agents;   four   participants   receiving   anactive   agent   had   died   by   suicide.   Because   of    concerns   involvingboth   SSRIs   and   AEDs,   it   is   pertinent   to   examine   the   effect   of    AED-moodstabilizers   on   suicidal   ideation   and   behavior   and   whetherthese   agents   may   add   to   the   risk   ofsuicidality,   when   received   inconjunction   with   SSRIs.   Thisclass   of    agents   (valproate,   carbamaz-epine,   oxycarbmazepine   (to   name   a   few)   is   often   prescribed   formood   stabilization   to   adolescents   who   either   do   not   respond   toSSRIs   alone,   or   present   with   symptoms   that   may   be   responsive   tothese   agents.Are-examination   of    the   suicide   rates   during   the   past   decade   hasshown   apuzzling   increase   with   the   United   States   (US)   experienc-ing   its   largest   ever   year-to-year   increase   (14%   between   2003   and2004)   since   the   Center   for   Disease   Control   (CDC)   firststartedsystematic   collection   ofsuicide   data   in   1979.   Similarly,   theNetherlands   had   experienced   adramatic   increase   of    49%for   thesame   period   (Gibbons   et   al.,   2007).Further,   independent   research-ersfound   that   the   rise   in   adolescent   suicide   rate   for   period   2003–2004   remained   largely   unchanged   for   2005   (Bridge   et   al.,   2008),which   bolstered   the   initial   concerns   that   the   increased   suicidalitynoted   during   2003–2004   was   possibly   associated   with   achange   inantidepressant-prescribing   practice.   However,   adecline   in   thesuicide   rate   in   2006   and   2007   to   6.9   per   100,000   has   beenreassuring.   Nevertheless,   longer   term   data   are   necessary   tounderstand   these   fluctuations   and   whether   the   FDA   warninghad   indeed   resulted   in   atemporary   change   in   clinical   practice   thatwasassociated   with   an   increased   suicide   rate   in   the   US   and   abroad.Clearly,   the   pharmacotherapy   of    adolescent   depression   continuestobe   fraught   with   concerns.Although,   it   is   beyond   the   scope   of    this   study   to   clarify   theoverall   association   between   suicidality   and   SSRIs,   we   describe   heresuicide-related   events   (SREs)   among   depressed   adolescents   whowere   acutely   suicidal   at   study   entry   and   were   receiving   aSSRIduring   a   3-month   period   following   apsychiatric   hospitalization.Additionally,   in   keeping   with   our   secondary   objective,   we   examinevariability,   if    any,   in   SRE-rates   among   subgroups   ofadolescentsreceiving   an   SSRI   alone,   or   in   combination   with   other   psychotropicmedications. 2.Methods  2.1.   Participants   and   study   design Data   were   extractedfromhospitalizedsubjectswho   hadparticipated   in   an   IRBapprovedpsychosocialinterventionstudy(YouthNominatedSupport   Team   –II,fundedbyNationalInstitute   ofMental   Health   [R01MH63881]; n =   448).Theinclusioncriteria   fortheparent   study   were:   (1)arecentsuicideattempt(during   the   pastmonth),orsevere,unrelentingsuicidalideation,   (2)   ages13–17years,   and   (3)parent   or   guardianinformedconsent   andadolescentassent.   Exclusion   criteriawere:   (1)severe   cognitive   impairmentand/oractivepsychosis,(2)direct   transferto   medical   unit,   (3)transfertoresidentialplacement,(4)lived > 40   miles   oronehour   driving   time   fromhospital(King   et   al.,2009).Fromthislarger   grouprecruitedfortheparent   study,additionaldata   were   extractedfor   asubgroup( n =   120)that   metthecriteria   forthepresentstudy:   (1)diagnosisof    anydepression,   based   on   theSchedulefor   AffectiveDisordersandSchizophreniaforSchool-AgeChildren   (definite,partiallyremittedor   probable   diagnoses   formajordepression,dysthymia,or   depressivedisorder   NOS)(KSADS-PL;Kaufmanetal.,1997);   (2)receiving   an   SSRI(either   aloneor   incombinationwith   other   psychotropic   agents,   butnotanothertypeof    antidepressant;i.e.,   tricyclic   antidepressant   and/orMAOI);(3)receiving   a   consistentmedication   regimen   duringthe3-month   follow-upstudyperiod.Although   220participantsinitiallymetthe   inclusioncriteria   for   thepresentstudy,   75(34.1%)   were   excluded   from   thefollow-up   analysesbecause   of lackof3-month   data,while25   (11.4%)   were   examinedseparatelybecause   of    changesmade   to   theirmedicationregimen.   Reasonswhy   or   thetimingwhen   the   SSRI,moodstabilizeror   an   antipsychotic   wereinitiated   were   notrecordedduring   thedata   collection.Alsonotavailable   were   theage   of onset   ofthedepressivedisorder. N.Ghaziuddin   et    al.    /     Asian    Journal   of    Psychiatry    xxx   (2014)    xxx–xxx 2 GModel AJP-582;   No.   of    Pages   7 Please   cite   this   article   in   press   as:   Ghaziuddin,   N.,   etal.,   Anaturalistic   study   of    suicidal   adolescents   treated   with   an   SSRI:Suicidalideation   and   behavior   during   3-month   post-hospitalization   period.   Asian    J.Psychiatry   (2014),   http://dx.doi.org/10.1016/ j.ajp.2014.03.014  The75participantslost   tofollow-upat   3monthswerecomparedto   the145adolescents   with   3-monthfollow-updata.Nosignificantdifferenceswere   foundbetween   the   retainedandthe   lost-to-follow-up   groupsinterms   ofdemographics,   thetypeor   theseverityof    psychiatricsymptoms.Of    the145adolescents   forwhom   wehadfollow   up   data,25   didnotremainin   thesame   medicationgroupthattheyhadstartedin.Therefore,thefinalgroup   consistedof    120   who   remainedonaconsistent   treatmentregimen,   in   additiontomeetingotherstudyrelatedcriteria.These   final   120   adolescents   were   grouped   on   the   basis   of    otherpsychotropic   medications   received   atstudy   entry,   in   addition   toanSSRI:   SSRIs   alone   (SSRI;   n =   71),   SSRI   combined   with   amoodstabilizer   (SSRI   +   MS;   n   =   17),   SSRI   combined   with   an   antipsychotic(SSRI   +AP;   n   =   20)   and   SSRI   combined   with   amood   stabilizer   andanantipsychotic   (SSRI   +   BOTH;   n   =12).   Adolescents   were   notexcluded   based   on   their   usage   of    ADHD   medication   (stimulant   ornon-stimulant)   or   a   benzodiazepine.  2.2.   Standardized   measures All   standardized   instruments   described   below,   except   forthe   Services   Assessment   Record   (SARS;    Jensen   et   al.,   2004   andtheCritical   Incident   Check   (CIC;   King,   2000,   unpublished)   werecompleted   at   study   entry.   These   two   instruments   (CIC   and   theSARS)   were   only   completed   at   3months.   Instruments   that   wererepeated   at   3   months   included   the   Children’s   Depression   Scale-Revised   (Poznanski   et   al.,   1984)   and   the   Suicidal   IdeationQuestionnaire   (Reynolds,   1988).The   KSADS-PL    (Kaufman   et   al.,   1997)   isa   semi-structuredclinical   interview,   designed   to   assess   the   presence   of    DSM-IVmental   disorders.   Interviewers   were   trained   mental   healthprofessionals   who   completed   20   hours   of    KSADS-PL    training   andestablished   inter-rater   reliability   with   asenior   diagnostician   onfour   consecutive   interviews   prior   to   study   onset.The   Children’s   Depression   Rating   Scale-Revised   (CDRS-R;Poznanski   and   Mokros,   1996)is   asemi-structured   interviewconducted   with   adolescents   to   assess   the   severity   of    depressivesymptoms   within   the   previous   two   weeks.   Inter-rater   reliability   inthe   study   was   high   (mean   alpha   across   raters   =   98).TheBeck   Hopelessness   Scale   (BHS;   Beck,   1988):   This   is   aself-report   measure   that   has   been   shown   to   have   good   internalconsistency   (with   a   KR-20   coefficient   of    0.86),   strong   concurrentvalidity   (indicated   by   apositive   correlation   with   depression[ r    =0.53],   and   a   negative   correlation   with   reasons   for   living[ r  =  0.65]   among   adolescent   psychiatric   inpatients.The   Suicidal   Ideation   Questionnaire-Junior   (SIQ-JR;   Reynolds,1988):   This   is   a15-item   self-report   questionnaire   for   assessing   thefrequency   of    suicidal   thoughts.   Higher   total   scores   indicate   higherseverity   of    suicidal   ideation.   Total   scores   on   the   SIQ-JR    haveshownhigh   internal   consistency   ( r  a  =   0.91)   and   test–retest   reliability( r  tt   =0.91)   (Mazza   and   Reynolds,   1999).TheYouth   Self-Report(YSR;Achenbach,   1991):   Thisisa   112-itemscalethat   assesses   a   broad   range   ofpsychopathology.   Ithastwo   broadbandscales(internalizing   and   externalizing)thathavedemonstratedgood   construct   validityandcorrelationswithrelatedself-report   measures(ThurberandHollingsworth,1992).   Forthesample   fromwhich   theseparticipants   wereselected(YST–IIstudy),internalconsistencywas   0.89fortheinternalizingscale   and0.86fortheexternalizing.Additionally,thereareeightnarrowbandsubscales(social   problems,thoughtproblems,attention   problems,   withdrawn,somaticcomplaints,anxious/depressed,delinquentbehavior,andaggres-sivebehavior).The   Multidimensional   Anxiety   Scale   for   Children   (MASC;   Marchetal.,   1997):   This   is   a   39-item   rating   scale,   completed   by   achild   oran   adolescent   toassess   abroad   spectrum   ofanxiety   symptoms.Each   item   is   scored   on   afour-point   Likert   scale.   The   MASC   hasdemonstrated   excellent   test–retest   reliability,   with   correlationcoefficients   among   adolescents   ranging   from   0.75   for   thePerfectionism   subscale   to   0.90   for   the   tense   subscale   (Marchand   Sullivan,   1999).The   Childand   Adolescent   SocialandAdaptive   FunctioningScale(CASAFS;   Priceet   al.,2002)is   a24   item   self-reportinventory   developedspecificallyto   examine   socialandadaptivefunctioning.Findingssupport   thescale’sreliability,   validity,   andsensitivitytothe   impactofa   depressivedisorder.   Subscalesincludeschool   performance,peerrelationships,family   relation-ship,andhome   duties/self-care.   Higherscores   indicatebetterfunctioning.The   Services   Assessment   Record   –Parent   Interview   (SAR;Preuss   and   King,   unpublished)   was   specifically   developed   to   assesstreatment   adherence   during   intervention   and   follow-up   periods.Its   structure   and   format   was   adapted   from   the   Services   Assessmentfor   Children   and   Adolescents   –   Parent   Interview   ( Jensen   et   al.,2004).The   SARS   was   used   to   obtain   information   at   3-monthfollow-up   assessment   regarding   medications,   medication   changes,psychosocial   treatments,   use   of    intensive   services   (e.g.,   psychiatrichospitalizations),   and   number   of    appointments   attended   formedication   and/or   psychosocial   treatment.The   Critical   Incidents   Checklist   (King,   2000,   unpublished)   isa15-item   self-report   measure   about   the   presence   and   number   of    avariety   of    adverse   events   for   the   interval   since   the   participant’s   lastcontact   with   the   study   team.   This   measure   includes   questionspertaining   to   history   of    abuse   with   responses   coded   as   a   ‘‘yes/no’’.The   Diagnostic   Interview   Schedule   for   Children-IV   (DISC-IV;Shaffer   et   al.,   2000)   records   suicide   attempts   in   the   past   year   andtheadolescent’s   lifetime.Suicide   Related   and   other   Emergency   (SRE)   is   a   compositecritical   incident   variable,   which   was   created   for   assessment   at   3-month   follow-up.   This   variable   is   based   on   aparent’s   or   theadolescent’s   report   about   asuicide   attempt,   psychiatric   hospitali-zation   (forany   reason),   or   suicide-related   visit   to   the   emergencydepartment.   This   variable   was   created   from   items   on   the   CICandtheDISC-IV.   It   is   important   to   note   that   the   YST-II   intervention(parent   study)   was   not   associated   with   areduction   in   adolescentsuicide   attempts   (King   et   al.,   2009).  2.3.   Data   analyses   and   results Analysesofbaselineclinicalfeatureswere   conducted   forthe220participantswho   hadmetthe   studycriteriainitially(regardless   of3-month   outcomedataor   consistency   ofmedica-tioncombination).Withinthis   sample,themedicationgroupsdifferedsignificantlyonbaseline   aggressivebehavior   ( F  [3]=   2.713,    p   =0.046)andbaselinethoughtproblems   ( F  [3]=   5.631,    p   =0.001)identified   on   YSR    subscales.Participantswhowere   prescribedSSRI+   AP   reportedsignificantlygreaterthoughtproblemsthanthoseprescribedSSRI   alone   or   SSRI   +   MS;however,thisgroup(SSRI   +   AP)   didnotsignificantly   differfromSSRI   +   BOTH.   Problems   with   aggressivebehavior   were   signifi-cantlymore   common   among   thoseprescribed   SSRI+   BOTH,thanamong   thoseprescribedan   SSRI   alone.There   were   no   other   groupdifferenceson   theYSR.Additionally,therewere   no   medicationgroupdifferences   for   theMASC   subscales,BHS,SIQ-JR,   CASAFS   orCDRS-R.Itshouldbe   noted   thatthesegroupdifferences(relatedtothoughtproblemsoraggression)were   notdetectedamong   the120whowere   furtherselectedforthe3-monthfollow   upanalyses;thiswas   possiblyrelatedtothesmallernumberof participants   ineach   group   andreducedstatisticalpower.   Forthepurposeof    thisstudy,thisgroupof    120is   designatedas   the‘‘consistentmedication   sample.’’ N.Ghaziuddin   et    al.    /     Asian    Journal   of    Psychiatry    xxx(2014)    xxx–xxx   3 G   Model AJP-582;   No.   of    Pages   7 Please   cite   this   article   in   press   as:   Ghaziuddin,   N.,   et   al.,   Anaturalistic   study   of    suicidal   adolescents   treated   with   an   SSRI:   Suicidalideation   and   behavior   during   3-month   post-hospitalization   period.   Asian    J.Psychiatry   (2014),   http://dx.doi.org/10.1016/ j.ajp.2014.03.014   2.4.   Consistent    medication   sample There   were   120   participants   who   continued   to   be   prescribedthesame   medication   combinations   during   the   3-month   post-hospitalization   period   (consistent   medication   groups).   Chi-squareand   ANOVA   analyses   indicated   no   difference   by   medication   groupfor   any   demographic   variables.   Among   this   group,   the   majority(90.8%)   was   participating   in   individual,   family,   or   group   therapy   atbaseline;   with   an   average   of    5.2   sessions   between   baseline   and   3-month   follow-up.   There   were   no   differences   between   themedication   groups   in   either   the   proportion   of    adolescents   intherapy   or   inthe   average   number   of    sessions   received.   See   Table   1for   racial/ethnic   breakdown,   parental   income,   education   andpsychotherapy   information   for   the   sample   and   by   medicationgroup. T  -Test   and   chi-square   analyses   revealed   no   differences   inage,sex,   or   race   between   the   120   (consistent   medication   group)adolescents   and   the   25   who   were   inconsistent   (non-consistentmedication   group;   medication   changes   weremade   at   request   of the   patient,   the   family   or   were   physician-directed).   Additionally,these   groups   did   not   differ   on   past   history   of    physical   [ x 2 (3)   =   2.77,  p =   0.429]   or   sexual   abuse   [ x 2 (3)   =   6.13,    p   =   0.106]   orbypsychiatric   hospitalization   in   either   parent.   However,   participantsin   the   non-consistent   medication   group   were   more   likely   to   be   infamilies   receiving   public   assistance   (16.7%   vs.   3.4%;   x 2 [1]   =   6.53,  p =   0.011)   and   scored   significantly   higher   on   MASC   total   scores   of adolescent   anxiety   ( t    [142]   =    2.32,    p   =   0.022).   The   mean   MASCscore   for   the   non-consistent   group   was   55.2   compared   with   45.7forthe   consistent   group.   There   were   no   other   differences   onany   other   measures   ofpsychopathology   (SIQ-JR,   CDRS-R,   BHS   andYSR-INT,   YSR-EXT).   Further,   there   were   no   differences   between   theconsistent   and   non-consistent   groups   in   terms   of    the   presence   of SREs   (attempts   or   hospitalizations)   at   the   3-month   time-point.  2.5.Differences   within   consistent-medication    groups Table   2presents   baseline   clinical   features   for   the   entireconsistent   medication   sample,   including   past   history   of    suicideattempts,   and   features   for   eachmedication   group   within   thislargergroup.   No   significant   group   differences   were   found   in   baselineclinical   features   or   suicide   attempt   history.   Table   3presents   co-morbid   diagnoses   for   the   overall   consistent   medication   group   andfor   each   medication   sub-group.   Specifically,   we   report   on   thepresence   of    any   anxiety   disorder,   PTSD   or   acute   stress   disorder,any   disruptive   behavior   disorder,   and   anysubstance   use   disorder.Chi-square   analyses   revealed   no   differences   in   the   presentation   of comorbid   diagnoses   between   the   medication   groups.  2.6.    3-Month   critical   incidents   and   outcomes Table   4   presents   descriptive   statistics   for   Suicide   RelatedEmergencies   (SREs),   3-month   SIQ-JR    scores,   and   the   3-monthchange   in   SIQ-JR    scores   for   eachof    the   consistent   medication   subgroups   and   the   overall   group.   For   the   overall   group   and   within   eachgroup,   there   was   a   decline   in   the   mean   3-month   SIQ-JR    scoresrelative   to   atstudy   entry   (SIQ-JR    for   overall   group   =47.15      20.04and   post   SIQ-JR    at   3   months   foroverall   group   =21.75    16.25;   seeTables   2   and   4   for   details).   Similarly   suicide   attempts   reported   by   the  Table   1 Demographic   characteristics   of    sample:   overall   and   bymedication   group.Overall n   =   120SSRI n   =   71MS n   =17AP n   =20BOTH n   =12Sex(%female)   74.2   74.682.4   60.0   83.3Race(%)White   (non-Hispanic)   80.8   78.976.5   85.0   91.7Black   (non-Hispanic)   5.05.6   11.8   0.0   0.0Other(non-Hispanic)   7.5   9.9   5.9   5.0   8.3Hispanic   5.8   5.6   5.9   10.0   0.0Age(mean   (SD))   15.51   (1.26)   15.60   (1.08)   15.72   (1.58)   15.12   (1.62)   15.30   (1.06)Income   (%) < $40,000   17.9   23.0   11.7   15.8   0.0$40–$80,000   35.7   36.935.3   31.6   36.4 > $80,000   46.4   40.0   52.9   52.7   63.6Family   on   public   assistance?   (%yes)   3.4   4.3   0.05.0   0.0Youthin   individual,   group,   or   family   therapy?   (%   yes   [mean   number   ofsessions])   95.4   (4.77)   93.8(4.35)   88.2   (6.53)   90.0   (4.59)   90.9   (4.91) Notes .SSRI   =   SSRI   alone,   MS=   SSRI   +mood   stabilizer,   AP   =SSRI   +   antipsychotic,   BOTH   =SSRI   +mood   stabilizer   and   aantipsychotic.  Table   2 Baseline   psychopathology   variables   for   consistent   medication   sample:   overall   and   bygroup.Overall n   =   120Mean   (SD)SSRI n =71Mean   (SD)MS n   =17Mean   (SD)AP n   =   20Mean   (SD)BOTH n =12Mean   (SD)SIQ-JR    47.15   (20.04)   46.65   (21.10)   44.53   (15.32)   50.65   (20.18)   48.00   (20.78)CDRS-R61.70   (12.08)   62.08   (12.62)   58.41   (10.83)   62.35   (12.08)   63.00   (11.10)MASC45.65   (18.87)   45.04   (18.76)   42.06   (17.34)   48.45   (21.97)   49.58   (16.95)BHS9.19(5.75)   9.30   (5.69)   6.53   (5.63)   10.65   (5.27)   9.92   (9.46)YSRinternalizing   28.30   (10.30)   27.88   (10.87)   26.12   (9.92)   31.15   (9.16)   29.00   (9.32)YSRthought   disruption   4.14(3.12)   3.84   (3.13)   3.53   (2.81)   5.65   (3.17)   4.25   (2.99)YSRexternalizing   19.78   (9.31)   18.63   (9.20)   19.76   (10.69)   21.65   (9.43)   23.42   (7.03)YSRaggression   problems   12.92   (6.49)   11.94   (6.13)   13.29   (8.05)   14.35   (7.03)   15.75   (4.29)Hasthe   youth   attempted   suicide   in   the   past   month?   (%   yes)   58.663.1   58.8   50.0   45.5Suicideattempts   –lifetimeNo   attempt   (%)   25.825.4   17.6   40.0   16.7Single   attempt   (%)   35.038.0   35.3   20.0   41.7Multiple   attempts   (%)   39.236.6   47.1   40.0   41.7 Notes .SSRI   =   SSRI   alone,   MS=SSRI   +   mood   stabilizer,   AP   =SSRI+   antipsychotic,   BOTH   =SSRI+   mood   stabilizer   and   aneuroleptic;   suicide   attempt   questions   are   based   on   childreporton   the   DISC. N.Ghaziuddin   et    al.    /     Asian    Journal   of    Psychiatry    xxx   (2014)    xxx–xxx 4 GModel AJP-582;   No.   of    Pages   7 Please   cite   this   article   in   press   as:   Ghaziuddin,   N.,   etal.,   Anaturalistic   study   of    suicidal   adolescents   treated   with   an   SSRI:Suicidalideation   and   behavior   during   3-month   post-hospitalization   period.   Asian    J.Psychiatry   (2014),   http://dx.doi.org/10.1016/ j.ajp.2014.03.014  entire   group   during   the   month   prior   tostudy   entry   declined   from58.6%   to   5%   reported   at3-month   follow   up   (Tables   2   and   4).   Chi-squared   analyses   revealed   significant   differences   between   medica-tion   groups   in   the   number   of    adolescent   or   parent   reportedpsychiatric   hospitalizations   ( x 2 [3]   =   16.41,    p   =0.001)   and   thenumber   of    overall   SREs   ( x 2 [3]   =   10.32,    p   =   0.016).   A   series   of    2    2Chi-square   tests   were   conducted   posthoc   todetermine   the   specificbetween-group   differences.   All   medication   augmentation   groups(SSRI   +   MS,   SSRI   +   AP,   SSRI   +   BOTH)   reported   significantly   elevatedlikelihood   of    apsychiatric   hospitalization   compared   with   thegroupreceiving   an   SSRI   alone,   (17.6%   vs.1.4%   forthe   mood   stabilizer   group, x 2 [1]   =   8.34,    p   =0.004;   30.0%   vs.   1.4%   for   the   antipsychotic   group,   x 2 [1]   =   17.97,    p   =   0.000;   16.7%   vs.1.4%   for   the   group   onBOTH,   x 2 [1]   =   6.86,    p   =   0.009).   Additionally,   those   receiving   an   SSRI   with   anantipsychotic   were   morelikely   to   report   an   SRE   than   those   receivingan   SSRI   alone   (40.0%   vs.   9.9%,   x 2 [1]   =   10.30,    p   =   0.001).   Therewere   noother   statistically   significant   differences   between   the   groups   intermsof    SREs,   hospitalizations,   or   suicide   attempts. Multiple   linear   regression   was   used   to   identify   which   variableshadinfluenced   the   suicidality   related   outcomes   among   themedication   groups.   The   dependent   variable   in   these   analyseswas   change   in   SIQ-JR    from   baseline   to   3   months   (a   negative   changevalue   for   an   individual   indicated   a   decrease   in   SIQ-JR    score).Covariates   were   scores   on   measures   that   differed   betweenmedication   groups   at   baseline   and   scores   on   measures   with   eitherconceptual   or   empirical   association   with   suicidality.   The   covariatesfor   the   test   of    suicidal   ideation   change   weremedication   group,   YSR aggression,   YSR    thought   problems,   hopelessness,   and   baselinereport   of    a   suicide   attempt.   The   overall   model   ( F  [5,117]   =3.27,  p   <   0.01)   accounted   for   12.7%   of    the   variance   in   change   scores.However,   only   two   predictors   individually   accounted   for   signifi-cantvariance   in   change   scores.   Higher   baseline   hopelessness   andaggression   scores   were   associated   with   greater   reduction   insuicidal   ideation   at3-months   (hopelessness:   b   =    1.13,  p <   0.001;   aggressive   behavior:   b   =    0.67,    p   =   0.003). 3.   Discussion The   main   findings   of    the   present   study   are:   (1)   adolescentsreported   adecline   in   suicidal   ideation   and   suicidal   behaviorsduring   a3-month   post-hospitalization   period;   (2)   decrease   insuicidal   ideation   at   3-month   follow   up,   irrespective   ofmedicationgroup,   was   associated   with   higher   baseline   hopelessness   andaggression;   (3)   statistically   higher   number   of    psychiatric   hospi-talizations   were   observed   in   groups   SSRI   +   MS   and   SSRI   +   BOTH,relativeto   SSRI   alone   group;   and   (4)   and   statistically   highernumber   of    SREs   were   found   in   group   SSRI   +   AP,   relative   toSSRIalonegroup.   Based   on   these   data,   although   we   cannot   shed   light   ontheFDAblack   box   warning,   we   concluded   that   suicidality   was   notexacerbated   during   treatment   with   an   SSRI   in   a   group   of adolescents   who   were   simultaneously   depressed   and   acutelysuicidal.   Increased   suicidal   related   outcomes   noted   in   those   whoreceived   combination   medication,   in   particular   those   who   receivedan   antipsychotic   agent   in   conjunction   with   an   SSRI,   most   likelysuggests   agreater   illness   severity   at   baseline.   Our   findings   alsounderscore   aconcern   that   has   been   raised,   thatit   is   important   toinclude   clinical   and   treatment   variables,   or   their   interaction,   whichare   often   excluded   from   the   assessment   of    suicide   relatedoutcomes   (Brent   etal.,   2009).A   major   strength   of    the   presentstudy   is   that   depressed   and   simultaneously   suicidal   adolescents,whoare   often   excluded   from   clinical   trials,   but   frequently   presentin   ‘‘real   life’’   clinic   settings,   were   included.Decline   in   suicide   attempts   reported   at   3-month   follow   uprelative   to   study   entry   should   be   viewed   in   context   of    the   studydesign.   Because   our   sample   comprises   adolescents   who   werepsychiatrically   hospitalized   with   suicide   risk   concerns,   all   medi-cationgroups   include   high   percentages   of    adolescents   who   madesuicide   attempts   in   the   past   month   (ranging   from   45.5%   to   63.1%).Ashas   been   shown   in   multiple   published   follow-up   studies   of suicidal   and   psychiatrically   hospitalized   adolescents   duringtheimmediate   post-hospitalization   period,   the   percentage   of   Table   3 Comorbid   diagnoses   for   consistent   medication   sample:   overall   andbymedication   group.Overall n =   120SSRI n   =71MS n   =17AP n   =   20BOTH n   =   12Presenceof    any   anxiety   disorder a 27.526.8   23.5   30.0   33.3Presenceof    PTSD   or   acute   stress   disorder   25.021.1   41.2   25.0   25.0Presenceof    any   disruptive   behavior   disorder b 37.535.2   29.4   60.0   25.0Presenceof    any   substance   usedisorder? c 16.718.3   17.6   5.0   25.0 Notes .Percentages   presented   aredefinite,   probable,   or   partially   remitted   presence   of    diagnosis,   all   diagnoses   are   based   on   K-SADD   interview. a Any   anxiety   disorder   excludes   PTSD   and   acute   stress   disorder;   includes   separation   anxiety,   panic   disorder,   avoidant   disorder,   simple   phobia,   social   phobia,   agoraphobia,generalized   anxiety   disorder,   andobsessive-compulsive   disorder. b Includes   attention   deficit/hyperactivity   disorder,   conduct   disorder,   oroppositional   defiant   disorder. c Includes   alcohol   andother   substances;   abuse   anddependence.  Table   4 Three-month   outcome.3-Month   analysis   by   groupSSRIMS   AP   BOTH   OverallYouthor   parent   reported   attempt   (%   yes)   5.60.0   10.0   0.0   5.0Youthor   parent   reported   psychiatric   hospitalization   (%   yes)   1.417.6 * 30.0   16.7 * 10.0SRE:Youth   or   parent   reported   suicide-related   emergency   (%   yes)   9.923.5   40.0 ** 16.7   17.53month   SIQ-JR    total   score   [mean   (SD)]   22.16   (17.21)   19.29   (7.78)   22.35   (17.39)   22.17   (18.74)   21.78   (16.25)3month   SIQ-JR    change   score   [mean   (SD)]    24.66   (23.85)    25.24   (16.82)    28.30   (17.35)    25.83   (19.94)    25.47   (21.41) Notes .SSRI   =SSRI   alone,   MS=SSRI   +mood   stabilizer,   AP   =SSRI+antipsychotic,   BOTH   =   SSRI   +   mood   stabilizer   andanantipsychotic,   suicide   attempt,   hospitalization,   andemergency   items   taken   from   the   CIC   andDISC;   negative   SIQ-JR    change   score   indicates   adecrease   insuicidal   ideation. * Significantly   different   from   SSRI   alone   (  p   <   0.01). ** Significantly   different   from   SSRI   alone   (  p <   0.001). N.   Ghaziuddin   et    al.    /     Asian    Journal   of    Psychiatry    xxx(2014)    xxx–xxx   5 G   Model AJP-582;   No.   of    Pages   7 Please   cite   this   article   in   press   as:   Ghaziuddin,   N.,   et   al.,   Anaturalistic   study   of    suicidal   adolescents   treated   with   an   SSRI:   Suicidalideation   and   behavior   during   3-month   post-hospitalization   period.   Asian    J.Psychiatry   (2014),   http://dx.doi.org/10.1016/ j.ajp.2014.03.014
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