Clinical use of second-generation antipsychotics in children

77 Scandina ian Jou nal o Child and Adolescen Psychia y and Psychology Vol. 5(2):77-88 (2017) DOI 10.21307/sjcapp-2017-009 Resea ch A icle Open Access Clinical use o second-gene a ion an ipsycho ics in child en Ki si Kakko1*, Leena Pihlakoski1, Raili Salmelin2, Päi i Keskinen3, Kaija Puu a1, Tuula Tamminen4 1Depa men o Child Psychia y, Tampe e Uni e si y Hospi al, Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, Finland; 2Depa men o Child Psychia y, Tampe e Uni e si y Hospi al, Facul y o Social Sciences/Heal h Sciences, Uni e si y o Tampe e, Finland; 3Depa men o Pedia ics, Tampe e Uni e si y Hospi al, Cen e o Child Heal h Resea ch, Uni e si y o Tampe e, Finland; 4Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, Finland *Co esponding au ho : [email p o ec ed] Abs ac Backg ound: The use o second-gene a ion an ipsycho ic (SGA) medica ion among child and adolescen psychia ic pa ien s has inc eased wo ldwide in ecen yea s. The inc ease appea s o ha e been mo e ex ensi e in he USA han in Eu opean coun ies, bu he endency is simila . Howe e , a e a peak he use seems o ha e declined in he USA. Simul aneously wi h he inc easing numbe s, he du a ion o SGA use has leng hened, indica ions ha e b oadened, and o -label use has inc eased. Despi e exis ing ollow-up ecommenda ions and e idence o he me abolic ad e se e ec s o SGAs in child en, esea ch e idence has no ansla ed in o clinical p ac ice. Objec i e: The aim o his s udy was o assess he clinical use and ollow-up p ac ices o SGA medica ion among child psychia ic pa ien s o one uni e si y hospi al in Finland. Me hod: This e ospec i e pa ien epo -based s udy was conduc ed a he Child Psychia ic Clinic o Tampe e Uni e si y Hospi al, Finland. The s udy sample consis ed o 133 pa ien s who we e younge han 13 yea s when ini ia ing SGA ea men and had an ongoing SGA medica ion du ing he s udy pe iod. The s udy sample was di ided in o wo g oups acco ding o diagnosis o examine whe he he e we e di e ences be ween pa ien s wi h an au is ic o a de elopmen al diso de (F83-84) and pa ien s wi h o he psychia ic diagnoses. Resul s: This s udy showed ha SGA use in child en younge han 13 yea s was mainly o -label. I espec i e o diagnosis, he mos common indica ion was agg ession. Especially child en wi h psychia ic diagnoses o he han de elopmen al diso de s had mul iple socio-demog aphic isk ac o s and ad e se li e expe iences in hei backg ound. The ollow-up p ac ices we e di e se and pa ly i egula . Conclusions: A need o sys ema ic SGA moni o ing p ac ices and dialogue be ween he medical speciali ies ea ing child en and hei amilies is e iden . Keywo ds: an ipsycho ic medica ion; second-gene a ion an ipsycho ic; child en; ollow-up p ac ices; ad e se li e e en s In oduc ion The use o second-gene a ion an ipsycho ic (SGA) medica ion among child and adolescen psychia ic pa ien s has inc eased wo ldwide in ecen yea s (1- 5). The inc ease appea s o ha e been mo e ex ensi e in he USA han in Eu opean coun ies, bu he endency is he same (3,6). Howe e , a e a peak, SGA use seems o ha e declined in he USA (7,8). A he same ime, he du a ion o SGA use in child en has leng hened, indica ions ha e b oadened, and o - label use has inc eased (3,9,10). The use o SGAs in child en and adolescen s seems o be inc easing om he age o 7 o 8 yea s onwa ds, p edominan ly in male pa ien s (2-5). In Finland, he p e alence o an ipsycho ic use among child en and adolescen s unde he age o 18 yea s has inc eased om 4.3 o 6.7/1000 be ween 2008 and 2015 (5). Simul aneously, he p opo ion o child en and adolescen s in his age g oup using an ipsycho ic medica ion and ha ing a diagnosis o a psycho ic diso de o psycho ic symp oms dec eased om 19% o 11% (5). Acco ding o he s a is ics o Second-gene a ion an ipsycho ics in child en 78 he Social Insu ance Ins i u ion o Finland, du ing he same pe iod, p e alence o use among child en younge han 13 yea s inc eased om 1.7 o 2.8/1000. The h ee mos commonly used SGAs in his age g oup we e ispe idone, a ipip azole, and que iapine. The numbe o child en younge han 13 yea s using hese d ugs in Finland has s eadily inc eased in ecen yea s, and he inc ease is mos appa en o a ipip azole (14- old) and ispe idone (1.5- old). Howe e , he p opo ion o child en younge han 13 yea s among all SGA use s in Finland has emained qui e s eady (1.4% o 1.6%) as he numbe o all use s has also inc eased (Figu e 1). Acco ding o a ecen Finnish s udy, SGAs we e he mos common medica ion among child psychia ic u gen -ca e in-pa ien s a Kuopio Uni e si y Hospi al, and he use was mos ly o -label (11). Yea 2008 2010 2012 2014 Numbe o use s 0 1000 2000 3000 100000 120000 140000 160000 Que iapine Rispe idon A ipip a zole All Q, R & A use s FIGURE 1. Second-gene a ion an ipsycho ic use o 0 o 12-yea -old child en and all use s in Finland (2008 o 2015) The o icial c i e ia o SGA use by child en younge han 13 yea s a y o some ex en among coun ies. In he USA, he Food and D ug Adminis a ion (FDA) app o es a ipip azole, que iapine, and ispe idone o he ea men o bipola diso de among child en olde han 10 yea s (12). A ipip azole and ispe idone a e also app o ed o he ea men o i i abili y associa ed wi h au ism (12). In Finland, only ispe idone and zip asidone a e app o ed o child en younge han 13 yea s. Zip asidone is app o ed o manic episodes o bipola disease in child en olde han 10 yea s and ispe idone o sho - e m use (≤6 weeks) in he ea men o conduc p oblems in child en olde han i e yea s wi h de elopmen al diso de s o men al e a da ion. As o icial indica ions o SGA use a e sca ce, use among child en is mos ly o -label (2). Child en and adolescen s wi h au ism spec um diso de s and in ellec ual disabili y ep esen an inc easing popula ion ea ed wi h SGAs (13). SGA use is also common among child en wi h a en ion de ici hype ac i i y diso de o dis up i e beha iou diso de s (2,3). SGA medica ion is also used o child en and adolescen s wi h a ious o he diagnoses – such as psychosis, mood and ic diso de s, and obsessi e compulsi e diso de – and in symp oma ic ea men o agg essi e beha iou despi e he p ima y diagnosis (1,2,8,10,14). When looking a he socio-demog aphic backg ound ac o s o paedia ic pa ien s using SGAs in he USA, s udies show ha he inc ease in SGA use has occu ed disp opo iona ely mo e o en among publicly han p i a ely insu ed pa ien s (1,7). Those in os e ca e seem o be especially p one o an ipsycho ic p esc ip ions among publicly insu ed child en (7). Child en in os e ca e ha e o en expe ienced auma ic li e e en s, which a e, among o he indi idual and en i onmen al ac o s, known isk ac o s o se e al men al heal h dis u bances (15-17). These kinds o expe iences a e p obably mo e common in child en and adolescen s ea ed by psychia ic se ices han in he gene al popula ion. Fo example, ad e se li e e en s we e equen among adolescen -aged psychia ic in-pa ien s su e ing om bipola diso de ype I (58%) and ca a onia (57%) (18). In a s udy by Fo d e al. (19), in a clinical sample o child psychia y ou -pa ien s aged ou o 18 yea s, one in h ee pa icipan s had a his o y o exposu e o in e pe sonal iolence. The e is some e idence o he bene i s o SGA use in child en. SGAs, pa icula ly ispe idone and a ipip azole, ha e shown o be e icien in he ea men o i i abili y, agg ession, sel -inju y, and possibly s e eo ypic beha iou in au ism (20-24). SGAs also appea o educe challenging beha iou in he sho e m among child en wi h in ellec ual disabili ies (25). The e is some e idence ha ispe idone has an e ec on dis up i e and agg essi e beha iou in he sho e m e en among child en and adolescen s wi h a no mal IQ (26,27). Rispe idone and a ipip azole appea o be p omising o ea ing ic symp oms in child en wi h Tou e e synd ome (28,29). Wi h psychosis o schizoph enia, he e icacy o SGAs appea s o be simila in child en, adolescen s, and young adul s (30-32). A ipip azole also appea s o be e ec i e in paedia ic bipola disease (30,33). Howe e , he a ailable s udies mos ly co e only he sho - e m use o SGAs, which seldom i s he clinical eali y. In child en, he he apeu ic p o ile and ad e se e ec s o SGAs seem o di e om hose in adul s, and child en also appea o be mo e ulne able han adul s o some SGA-induced ad e se e ec s (34). Seda ion, hype p olac inemia, and me abolic dis u bances, such as weigh gain, dyslipidaemia, and hype glycaemia, a e known SGA ad e se e ec s ha Second-gene a ion an ipsycho ics in child en 79 can ha e a - eaching consequences h ough me abolic, endoc inological, ca dio ascula , and psychological e ec s (34-38). We also know e y li le abou he long- e m e ec s o SGAs on he de eloping cen al ne ous sys em. The de ec ed inc ease in SGA use has induced a emp s o moni o and imp o e SGA p esc ip ion p ac ices a ound he wo ld (7,39,40). All moni o ing ecommenda ions emphasize on he app op ia e use o psychosocial in e en ions and he egula moni o ing o me abolic and o he ad e se e ec s (41). The guidelines o he Ame ican Academy o Child and Adolescen Psychia y (AACAP), he Canadian Alliance o Moni o ing E ec i eness and Sa e y o An ipsycho ics in Child en (CAMESA), and he Na ional Ins i u e o Heal h and Ca e Excellence (NICE) in he UK include ecommenda ions o moni o ing and managing he ad e se e ec s o SGA in child en (Table 1) (39,40,42). In Finland, he e a e na ional clinical guidelines o he ea men o schizoph enia in adul s, bu no o child en. Psycho opic medica ions a e howe e , ecommended o be ini ia ed o child en in specialis -le el heal h ca e se ices (5), wi h he excep ion o a en ion de ici hype ac i i y diso de medica ion (me hylphenida e). TABLE 1 . Recommenda ions o moni o ing second - gene a ion an ipsycho ic ea men acco ding o Na ional Ins i u e o Heal h and Ca e Excellence (NICE), Ame ican Academy o Child and Adolescen Psychia y (AACAP), and Canadian Alliance o Moni o ing E ec i eness and Sa e y o An ipsycho ics in Child en (CAMESA) (39,40,42) Follow - ups Issued by Baseline 1 2 3 4 NICE Weekly ( i s 6 weeks) 12 weeks E e y 6 mon hs G ow h cha *, WHC, RR, pulse, b- gluc, HbA 1c , lipids, p olac in, MD, nu i ional s a us, die , physical ac i i y G ow h cha , MD, e icacy, side-e ec s G ow h cha , MD, RR, pulse, b-gluc, HbA 1c , lipids, p olac in, physical heal h, e icacy, side e ec s G ow h cha , MD, WHC, RR, pulse, b-gluc, HbA 1c , lipids, p olac in, physical heal h, e icacy, side e ec s – AACAP Regula in e als Family his o y, BMI, WC, RR, pulse, b-gluc, lipids, MD BMI, RR, pulse, b-gluc (HbA 1c i needed), lipids † , MD – – – CAMESA 1, 2, 9 mon hs 3 mon hs 6 mon hs 1 yea G ow h cha , BMI, WC, RR, NEU, b- gluc, insulin, lipids, ASAT, ALAT, TSH (wi h que iapine), p olac in G ow h cha , BMI, WC, RR, NEU G ow h cha , BMI, WC, RR, NEU, b-gluc, insulin, lipids, p olac in G ow h cha , BMI, WC, RR, NEU, b-gluc, insulin, lipids ASAT, ALAT, TSH (wi h que iapine) Same as baseline No e. ECG ecommenda ions a e no included ALAT, alanine amino ans e ase; ASAT, aspa a e amino ans e ase; b-gluc, as ing glucose; HbA1c, glycosyla ed hemoglobin; lipids, blood lipid p o ile; MD, mo emen diso de s; NEU, neu ological examina ion; TSH, hy oid-s imula ing ho mone; RR, blood p essu e; WC, wais ci cum e ence; WHC, wais and hip ci cum e ence *Includes weigh and heigh †I signi ican weigh changes and/o a amily his o y indica ing isk Second-gene a ion an ipsycho ics in child en 80 Recommenda ions and ollow-up p o ocols seem o be help ul in clinical wo k and appea o inc ease moni o ing and possibly ha e an e ec on p esc ibing p ac ices (7,43,44). Despi e he al eady exis ing ecommenda ions, he e has been a lag in he ansla ion o esea ch e idence in o clinical p ac ice (39,45). Ra es o me abolic moni o ing o SGA ha e been low acco ding o se e al s udies. Rodday e al. (46) ound ha 66% o psychia is s epo ed ou inely asking abou he pa ien ’s medical his o y, 92% epo ed moni o ing he pa ien ’s g ow h, 81% epo ed moni o ing he pa ien ’s plasma glucose and lipids, 23% epo ed measu ing he pa ien ’s wais ci cum e ence, and 12% epo ed moni o ing he pa ien ’s ECG. Being able o measu e i al signs, heigh , and weigh on si e was associa ed wi h a highe p obabili y o moni o ing heigh and weigh (46). In an audi pe o med in he UK, Pasha e al. (44) disco e ed ha o in-pa ien s a a child and adolescen men al heal h uni , he pa ame e s measu ed mos o en be o e SGA ini ia ion included BMI and hip- o-wais ci cum e ence; howe e , he moni o ing a e o hese measu emen s was only 60%. In he USA, many moni o ing ini ia i es ha e aken place in he os e ca e sys em, and as a esul , SGA- ea ed child en in os e ca e a e now mo e likely han o he publically insu ed child en o ecei e me abolic moni o ing, and, in addi ion, psychosocial in e en ions (7). Ne e heless, bo h glucose and lipid moni o ing ailed in 72% o hese os e child en and in 82% o o he s (7). Some child en appea o be mo e ulne able han o he s in de eloping me abolic ad e se e ec s, and an impo an goal o an SGA moni o ing p ocedu e should be o iden i y as ea ly as possible hose child en who a e a pa icula isk o ad e se e ec s (36,47). Some speci ic genes ha e al eady been linked wi h he inc eased isk o ad e se e ec s wi h SGAs, bu he e a e no gene es s a ailable ye in e e yday clinical wo k (47,48). In he ligh o cu en e idence, sc eening and moni o ing p ac ices should hus be emphasized. Aims o he s udy The aim o his s udy was o assess he clinical use, indica ions, and ollow-up p ac ices o SGA medica ion among child psychia ic pa ien s a Tampe e Uni e si y Hospi al (TAUH), Finland. This s udy also aims o desc ibe he medical and socio- demog aphic backg ound ac o s o SGA- ea ed child en as well as he possible bene i s and ad e se e ec s o SGA medica ion. Me hod This s udy was conduc ed a he Child Psychia ic Clinic o TAUH and was based on pa ien epo s. Wi h a ca chmen a ea o app oxima ely hal a million people, TAUH is one o i e uni e si y hospi als in Finland o e ing specialis -le el heal h ca e se ices. The Child Psychia ic Clinic gi es in- pa ien and ou -pa ien se ices o child en aged 0 o 12 yea s. Child en aged 13 o 18 yea s a e aken ca e o in adolescen psychia y, which in Finland is a sepa a e speciali y. Child en wi h a diagnosis o men al e a da ion a e e e ed o sepa a e se ices. Child en a e e e ed o TAUH by he heal h ca e cen es and communi y hospi als o he dis ic . Guidelines a e a ailable o he e e al p ac ices o specialis -le el child psychia ic se ices. Du ing he s udy pe iod (1 Oc obe 2013 o 1 Oc obe 2014), 1633 child en we e ea ed a he clinic. The inclusion c i e ia o he s udy we e ha he pa ien was younge han 13 yea s when ini ia ing SGA ea men , ha he medica ion was ini ia ed a he TAUH clinic, and ha he SGA medica ion was ongoing du ing he s udy pe iod. These c i e ia we e me by 133 pa ien s, whose pa ien epo s we e examined un il he da e he medica ion was discon inued, he pa ien was e e ed o ano he clinic, o un il 31 May 2015, whiche e came i s . The i s au ho (K.K.) collec ed in o ma ion om he pa ien epo s and eco ded hem. Selec ed pa ien epo s we e e iewed by he second au ho (L.P.), who also o e ed second opinion on eques om he i s au ho . The da a collec ed om pa ien epo s consis ed o he pa ien ’s age, he conclusion o he cogni i e e alua ion, and o he socio- demog aphic and medical ac o s a he SGA ini ia ion phase. The conclusions o cogni i e e alua ions we e dicho omized as in elligence wi hin no mal a ia ion o below, based on pa ien epo ma kings o ei he he a ending physician o a psychologis . In o ma ion on SGA medica ion use (gene ic name, du a ion, easons o discon inuing o changing medica ion) and o he psycho opic medica ions as well as in o ma ion on he pa ien ’s diagnoses and indica ions (o main symp oms) a ached o he SGA ini ia ion we e collec ed o deduced om he pa ien epo s. The easons o discon inua ion o changing he SGA we e ca ego ized o analyses by he i s au ho as: ad e se e ec , no bene i s, ad e se e ec s mo e signi ican han possible bene i s (un a ou able isk– bene i a io), symp oms diminished so ha he medica ion was no longe needed, and no in o ma ion. In addi ion, in o ma ion on he psychia ic and o he medical his o y o he pa ien and his/he amily was eco ded. The possible bene i s and ad e se e ec s o SGA medica ion we e ex ac ed om he physicians’ e alua ions eco ded in he pa ien epo s. The a ailable in o ma ion o possible bene i s was classi ied as: conside able Second-gene a ion an ipsycho ics in child en 81 bene i , some bene i , unce ain, no bene i , and no in o ma ion. The ad e se e ec s, such as weigh gain, and neu ological, endoc inological (e.g., gynecomas ia, mens ua ion dis u bances), and o he men ioned e ec s we e eco ded sepa a ely. In o ma ion conce ning he ollow-up p o ocols, such as medical e alua ions made du ing he ollow- up pe iod (physical s a us, weigh , and heigh ) and possible consul a ions made by child psychia is s o o he medical special ies (e.g., ca diology o paedia ics) we e eco ded. The pa ien ’s age- adjus ed BMI sco e was calcula ed a he analysis phase om he exis ing weigh and heigh da a (i bo h measu emen s we e a ailable om he same ime poin ) using he ables o he new Finnish g ow h e e ences (49). To examine whe he he e we e any di e ences be ween pa ien s ha ing an au ism spec um o de elopmen al diso de diagnosis and pa ien s wi h o he psychia ic diagnoses, he s udy sample was di ided in o wo g oups based on diagnosis using he In e na ional S a is ical Classi ica ion o Diseases and Rela ed Heal h P oblems, 10 h Re ision (ICD-10) (50). The i s g oup ( he PDD/DD g oup) consis ed o 40 (30%) child en wi h a pe asi e de elopmen al diso de (F84) diagnosis and se en (5%) pa ien s wi h a diagnosis o mixed speci ic de elopmen al diso de s (F83). The second g oup ( he non- PDD/DD g oup) consis ed o 86 (65%) pa ien s wi h a ious o he diagnoses. Resul s o he g oups whe e he e a e s a is ically signi ican di e ences a e epo ed sepa a ely; o he wise, he esul s a e epo ed o he en i e sample. The esul s o ca ego ized a iables a e epo ed as equencies (pe cen ages o numbe o cases, as app op ia e). Fo no mally dis ibu ed con inuous a iables, means (M) and s anda d de ia ions (SD) a e gi en, and o o he con inuous a iables, medians and qua iles (Md, Q 1 , Q 3 ) a e epo ed. Fo es ing he signi icance o di e ences be ween he PDD/DD and non-PDD/DD g oup, Pea son’s chi- squa ed es , Fishe ’s exac es , o he Mann– Whi ney U- es we e used, as app op ia e. A p- alue o less han 0.05 is conside ed signi ican , and a alue be ween 0.05 and 0.10 is conside ed indica i e; alues up o 0.10 a e epo ed. SPSS .23 was used o all s a is ical analyses. Resul s Eigh y-one pe cen o he s udy sample we e boys. The mean age a he ime o SGA ini ia ion was 9.3 yea s (SD, 2.1 yea s). In he PDD/DD g oup, he child en we e younge a he ime o SGA ini ia ion han he child en in he non-PDD/DD g oup (M 8.6 yea s, SD, 2.0; and M, 9.7 yea s, SD, 2.0, espec i ely; p = .002). The age dis ibu ion o he pa ien s showed wo peaks, one du ing he ea ly yea s o school (6 o 8 yea s) and he second a p e-pube y (11 o 12 yea s). Cogni i e e alua ion was pe o med o 85% o he child en, and a conclusion abou in elligence s a us was a ailable o all bu h ee o hem. Eigh y- one pe cen o hose e alua ed had an in elligence p o ile wi hin no mal age a ia ion. One pa ien had a diagnosis o men al e a da ion. In o ma ion on whe he he cogni i e e alua ion was pe o med o no was lacking in ou pa ien epo s. Cogni i e e alua ion was pe o med mo e equen ly in he PDD/DD g oup han in he non-PDD/DD g oup (96% s. 78%, p =.010), bu he e we e no s a is ically signi ican di e ences be ween g oups in he esul s o he e alua ions. Se en y-nine pe cen o he s udy pa ien s had been ea ed a leas once in hei li e ime a a psychia ic in-pa ien wa d. The mos common SGA d ug a ini ia ion was ispe idone (93%). Que iapine (6%) and a ipip azole (2%) we e less common. Rispe idone was indica i ely mo e common han o he SGAs in he PDD/DD g oup han in he non-PDD/DD g oup (98% s. 90%, p = .097). Six een pe cen o he pa ien s had hei medica ion swi ched o ano he SGA once, 6% wice, and wo pa ien s h ee imes. The mos common easons o swi ching he SGA we e ad e se e ec s (52%) and an un a ou able isk– bene i a io – ha is, he a ending physician had judged ha ad e se e ec s we e mo e signi ican han possible bene i s (48%). Thi y- wo pe cen o he pa ien s who had hei SGA swi ched had no bene i s om he ini ia ion d ug. In he PDD/DD g oup, he e we e ewe al e a ions in SGA medica ions han in he non-PDD/DD g oup (17% s. 34%, p = .035), and he eason o swi ching was less equen ly an ad e se e ec (31% s. 73%, p = .032). Pa ien s who discon- inued medica ion Du a ion o SGA medica ion (mon hs; median and qua iles) 0 10 20 30 40 50 60 All pa ien s All Non-PDD/DD PDD/DD All Non-PDD/DD PDD/DD p = 0.036 p < 0.001 FIGURE 2. Du a ion o second-gene a ion an ipsycho ic (SGA) medica ion. Figu es in he “all pa ien s” g oup do no desc ibe he genuine du a ion o SGA medica ion because he du a ion a e he endpoin o he ollow-up is no known Second-gene a ion an ipsycho ics in child en 82 Figu e 2 shows he du a ion o SGA medica ion in his s udy. Almos one- i h o he pa ien s discon inued medica ion comple ely du ing he s udy pe iod. The median du a ion o SGA medica ion among hese pa ien s was 14.4 mon hs. In he PDD/DD g oup, he du a ion o SGA ea men was longe han in he non-PDD/DD g oup (Md, 22.7 s. 10.8 mon hs, p = .036). The mos common easons o discon inua ion we e ha he pa ien ’s symp oms had diminished o a le el whe e medica ion was no longe needed (52%) o ha he isk–bene i a io was conside ed un a ou able (30%). When aking all s udy pa ien s in o accoun , he median du a ion o SGA medica ion by he end o he s udy pe iod was 22.2 mon hs. In he PDD/DD g oup, he du a ion was longe han in non-PDD/DD g oup (Md, 33.7 s. 18.4, p < .001). Howe e , his igu e does no desc ibe he ac ual du a ion o SGA medica ion in his g oup because he du a ion a e he end o ollow-up is no known. TABLE 2. In e na ional S a is ical Classi ica ion o Diseases and Rela ed Heal h P oblems, 10 h Re ision , diagnoses o second - gene a ion an ipsycho ic (SGA)- ea ed child en (n=133) Diagnoses ICD - 10 class % Hype kine ic diso de s F90 50 Conduc /mixed conduc and emo ional diso de F91 - 92 40 Pe asi e de elopmen al diso de s F84 30 Obsessi e compulsi e diso de F42 13 Diso de s o social unc ioning wi h onse speci ic o childhood and adolescence * F94 13 Reac ion o se e e s ess/adjus men diso de s F43 10 Tic diso de s F95 8 Emo ional diso de wi h onse speci ic o childhood F93 7 Diso de s o psychological de elopmen F80 - 82 7 Dep essi e episode F32 6 Bipola a ec i e diso de F31 5 Psycho ic diso de s F23, F29 5 Mixed speci ic de elopmen al diso de s F83 5 O he mood (a ec i e) diso de s F38 5 Phobic and o he anxie y diso de s F40 - 41 3 Dissocia i e (con e sion) diso de s F44 3 O he beha iou al and emo ional diso de s wi h onse usually occu ing in childhood and adolescence † F98 2 Ea ing diso de s F50 1 Unspeci ied men al e a da ion F79 1 No e. Each child could ha e mo e han one diagnosis ICD-10, In e na ional S a is ical Classi ica ion o Diseases and Rela ed Heal h P oblems, 10 h Re ision *Reac i e a achmen diso de F94.1 (n=5), o he childhood diso de s o social unc ioning F94.8 (n=12) †Non-o ganic enu esis F98.0 (n=1), non-o ganic encop esis F98.1 (n=1) Polypha macy was common among he pa ien s in he s udy. Nine pa ien s we e simul aneously using ano he an ipsycho ic medica ion, mos commonly ( i e pa ien s) le omep omazine. The ac ual a e o simul aneous use o wo di e en an ipsycho ic agen s was highe due o c oss- i a ion pe iods when swi ching om one medica ion o ano he . Six y- eigh pe cen o he s udy pa ien s had unde gone a leas a sho - e m ea men ial wi h some o he psycho opic medica ion (no including mela onin) in addi ion o SGA du ing hei ea men a he Child Psychia ic Clinic. Fi y- h ee pe cen had used one medica ion o he han SGA and 14% wo o h ee. The use o me hylphenida e was mo e common in he PDD/DD g oup han in he non- PDD/DD g oup (79% s. 58%, p = .022). Twen y- i e pe cen had had a leas a ial wi h a omoxe ine and 16% wi h selec i e se o onin eup ake inhibi o s. Fou een pe cen o he s udy pa ien s had had benzodiazepines as equisi e medica ion a some poin o hei ea men . Almos wo- hi ds (63%) o he pa ien s had unde gone a leas a sho - e m mela onin ea men o sleep p oblems. All o he s udy child en had a leas one ICD-10 F-ca ego y psychia ic diagnosis (50) a he ime o SGA ini ia ion and 75% had a leas wo F diagnoses, he maximum being ou (Table 2). Child en in he PDD/DD g oup had mo e o en como bid diso de s, 55% o hem ha ing wo F ca ego y diagnoses and 38% ha ing h ee o ou , while he espec i e numbe s in he non-PDD/DD g oup we e 47% and 19% (p = .001). The mos common diagnoses in he non-PDD/DD g oup we e F91-92 (conduc /mixed conduc and emo ional diso de ; 49%, n = 42) and F90 (hype kine ic diso de s; 44%, n = 38). F91-92 and F31 (bipola a ec i e diso de ) diagnoses we e mo e common in he non-PDD/DD g oup han in he PDD/DD g oup (49% s. 23%, p Second-gene a ion an ipsycho ics in child en 83 = .005, and 8% s. none, p = .051, espec i ely). Thi y-nine pe cen o he pa ien s had also a leas one ICD-10 Z diagnosis ( ac o s in luencing heal h s a us and con ac wi h heal h se ices), implying mul iple en i onmen al ac o s in luencing he pa ien ’s men al well-being. The indica ion o SGA ini ia ion was clea ly s a ed in 61% o pa ien epo s. In gene al, indica ions and symp oms we e di e se, and 92% o he pa ien s had wo o mo e indica ions o main symp oms. The mos common indica ions o co e/main symp oms o SGA ini ia ion we e agg ession (in 75% o he pa ien s) and beha iou p oblems (74%) independen o diagnosis. Mood swings we e a mo e common indica ion in he non-PDD/DD g oup (24% s. 9%, p = .035) and sleep p oblems as indica ion indica i ely associa ed wi h he PDD/DD g oup (17% s. 6%, p = .063). The o icially app o ed c i e ia o SGA medica ion (he e ispe idone, which was he mos commonly used SGA in his s udy) use in Finland is sho - e m ea men o conduc p oblems o child en olde han 5 yea s wi h de elopmen al diso de s o men al e a da ion. None o he SGA-medica ed child en in his s udy ul illed all hese c i e ia. Wi h loose in e p e a ion, he 47 (35%) pa ien s in he PDD/DD g oup ul illed he o icial c i e ion o diagnosis o de elopmen al diso de s o men al e a da ion. Fo y- i e o hese pa ien s also ul illed he c i e ion o age (> 5 yea s) and 34 ul illed he indica ion c i e ion o agg ession/agg essi e beha iou , bu in none o he s udy pa ien s was he medica ion sho - e m. TABLE 3. Family backg ound o he second - gene a ion an ipsycho ic - ea ed child en All (%) PDD/DD (%) Non - PDD/DD (%) p Family s a us (n=133) <.001 Biological pa en s 37 57 26 Pa en al sepa a ion 40 36 42 Fos e home 18 6 24 O he (e.g. adop ion) 5 0 8 Numbe o siblings (n=126) NS None 21 23 20 One 38 40 37 Two o mo e 41 36 43 Mo he ’s wo king s a us (n=133) .018 Wo king a leas pa ime 53 68 45 O he o no known 47 32 55 Fa he ’s wo king s a us (n=133) NS Wo king a leas pa ime 57 64 54 O he o no known 43 36 47 Alcohol/d ugs (n=83) 60 44 71 .021 Psychia ic his o y o i s - deg ee ela i es Schizoph enia, bipola disease o o he psychosis (n=67) 33 15 45 .016 Dep ession (n=88) 67 61 72 NS Suicide (n=133) NS Commi ed 2 2 2 A leas one a emp 7 2 9 Child exposed o iolence (n=133) 41 30 48 .065 Exposed o domes ic iolence 11 4 15 Been objec o physical punishmen o o he domes ic iolence 12 13 12 Bo h exposed and been objec 11 6 13 O he kind o iolence exposu e (e.g. wa expe iences) 8 6 8 No e. In a iables conce ning suicide and exposu e o iolence, missing in o ma ion was ca ego ized as “no”. In all o he a iables missing in o ma ion was sepa a ed. The e o e, he o al numbe o cases a y by a iable Second-gene a ion an ipsycho ics in child en 84 The s udy pa ien s had di e se social s ess ac o s and ad e se li e e en s in hei pas (Table 3). Less han 40% o he pa ien s had bo h biological pa en s as ca egi e s a he ime o SGA ini ia ion. Pa en al sepa a ion was common (40%), and 18% o he pa ien s we e in os e ca e. The e was pa en al subs ance abuse in mo e han hal o he amilies. A amily his o y o psychia ic diso de s was eco ded o 84% o he pa ien s (whe eas a amily his o y o soma ic diseases was eco ded o 53% o he pa ien s). The e was a i s -deg ee amily membe who had a diagnosis o schizoph enia, bipola disease, o o he psychosis in one- hi d o he amilies. O e a hal o he pa ien s had a dep essed amily membe and abou one- en h had a amily membe who had a emp ed o commi ed suicide. Exposu e o some kind o iolence was men ioned in 41% o he pa ien epo s. The e e yday unc ioning o he pa ien ’s pa en s in he PDD/DD g oup appea ed o be be e han ha in he non-PDD/DD g oup. Abou hal o he mo he s and a he s o he s udy pa ien s we e wo king a leas pa ime. Howe e , he employmen o mo he s was s a is ically signi ican ly mo e common in he PDD/DD g oup han in he non- PDD/DD g oup, and child en in he PDD/DD g oup also had bo h biological pa en s as ca egi e s mo e o en. In he PDD/DD g oup, ou -o -home placemen s we e a e han in he non-PDD g oup, and he e was signi ican ly less pa en al subs ance abuse and ewe i s -deg ee ela i es wi h bipola o o he psychoses. Exposu e o iolence was also indica i ely less common in he PDD/DD g oup han in he non-PDD/DD g oup (see Table 3). In 36% o he pa ien epo s, he e was no in o ma ion on g ow h his o y a he ime o SGA ini ia ion. When epo ed, g ow h his o y was no mal in 68% o he pa ien s, while he e was some de iance (e.g., o e weigh , slow g ow h) in he emainde p io o SGA ini ia ion. Six pa ien s we e epo ed o ha e been d inking alcohol and i e pa ien s we e epo ed o be smoking. One o he pa ien s had olun a ily old he physician abou expe imen al subs ance use. In gene al, in o ma ion on he pa ien ’s possible subs ance use was missing. In 81% o he cases, he a ending physician epo ed ei he conside able o a leas some bene i due o he SGA medica ion. Th ee pe cen had no bene i s om he SGA medica ion. In 16% o he cases, he possible bene i s emained unce ain o he in o ma ion was lacking. In many cases, he e was also luc ua ion in symp oms despi e he medica ion. In 28% o he cases, he a ending physician epo ed no ad e se e ec s. One ad e se e ec was epo ed in 32% o he pa ien s and 40% had wo o mo e ad e se e ec s. The mos equen ad e se e ec s we e inc eased appe i e and weigh gain, which we e epo ed in 36% and 35% o he cases, espec i ely. Somnolence, usually in he SGA ini ia ion phase, was epo ed in 33% o cases and o he neu ological ad e se e ec s in 10% o he pa ien epo s. All o he epo ed ad e se e ec s (inc eased i i a ion, mammilla y gland symp oms, dis u bances in mens ual cycle, u ina y symp oms, headaches, nosebleeds, abdominal pain o swelling, and loss o appe i e) we e each men ioned a mos in 7% o he pa ien epo s. Numbe o child en 0 20 40 60 80 100 120 140 Labo a o y es s BMI measu emen s Physical examina ion Baseline 0 10 20 30 40 50 60 70 Labo a o y es s BMI measu emen s Physical examina ion 6-12 mon hs Labo a o y es s BMI measu emen s Physical examina ion 0-6 mon hs Numbe o child en 0 10 20 30 40 50 60 70 Labo a o y es s BMI measu emen s Physical examina ion o e 24 mon hs Labo a o y es s BMI measu emen s Physical examina ion 12-24 mon hs 0 1-2 3-5 6-8 > 8 Numbe o measu emen s Du a ion o medica ion FIGURE 3. Physical examina ion, BMI measu emen s, and labo a o y es s pe o med du ing he second-gene a ion an ipsycho ic ea men Figu e 3 shows a summa y o he equency o physical examina ion, labo a o y es s, and BMI measu emen s pe o med du ing he s udy pe iod. A SGA ini ia ion (baseline), some kind o physical examina ion o he han measu emen o heigh o weigh was pe o med on 33% o he pa ien s. Almos he same p opo ion o he pa ien s (29%) had no physical examina ion du ing ollow-up. App oxima ely one- i h o he pa ien s in he longes ea men ca ego y (o e 24 mon hs) had no physical examina ions du ing ollow-up. A baseline, 38% o he pa ien s had hei weigh measu ed and 34% had hei heigh measu ed. Twen y pe cen had Second-gene a ion an ipsycho ics in child en 85 hei heigh measu ed once and 69% had hei heigh measu ed wice o mo e o en du ing he ollow-up. Weigh was measu ed once in 16% o he pa ien s, and 77% had a leas wo weigh measu emen s du ing he ollow-up. Ten (8%) pa ien s had no in o ma ion on weigh and ou een (11%) pa ien s had no in o ma ion on heigh du ing he ollow-up. In some epo s, i was men ioned ha g ow h was ollowed elsewhe e, bu he in o ma ion did no always each he a ending physician. Baseline labo a o y es s we e mo e equen han physical examina ion. A baseline, some labo a o y es s we e pe o med o 67% o he pa ien s and plasma lipids and glucose, as indica o s o me abolic condi ion, we e checked o 55% and 61% o he pa ien s, espec i ely. Twen y- i e pe cen o he pa ien s had one and 10% wo o h ee consul a ions wi h a paedia ic ca diologis du ing he s udy pe iod. A consul a ion was mos o en pe o med as a pape consul a ion. Indica ions o consul a ions we e di e se, bu mos ly in ol ed he in e p e a ion o an ECG i he psychia is conside ed i abe an . The ca diologis did no ind absolu e obs acles o SGA use in any o he consul a ions. Howe e , in wo pa ien s, ca diological ad e se e ec s (p olonged QT in e al) we e men ioned as a eason o discon inuing o swi ching he SGA. O he paedia icians (e.g., neu ologis o endoc inologis ) we e consul ed a leas once o 32% o he pa ien s. Nine pa ien s we e e e ed o a nu i ionis o die a y ad ice. Discussion In his s udy we assessed he clinical use o SGAs in 133 child psychia ic pa ien s aged 12 yea s o younge . Child en in he s udy had mul iple diagnoses, and polypha macy was common. Mos (79%) o he pa ien s had had in-pa ien ea men , e lec ing hei symp om se e i y and poo unc ional capaci y. Como bidi y was common, wi h 75% o all child en ecei ing mo e han one psychia ic diagnosis. Independen ly o he diagnoses, he main SGA a ge symp om was agg ession; howe e , he indica ion was clea ly s a ed in only 61% o he pa ien epo s. The o icial indica ions o SGA medica ion o child en younge han 13 yea s a e ew. Ne e heless, hese medica ions a e equen ly used o a ying indica ions in his age g oup (1,2,8,10,14). In his s udy, he da a we e collec ed om a geog aphically es ic ed a ea in Finland. Howe e , he indings a e in line wi h p e ious s udies (2,10,11). SGA use was mos ly o -label, since none o he pa ien s ul illed all o he o icial indica ion c i e ia. Va ious s udies show ha he signi ican isk o me abolic and o he SGA-induced ad e se e ec s calls o app op ia e moni o ing (34-38). Howe e , he con en and schedule o he physical e alua ions and ollow-up p ac ices o SGA medica ions ha e been di e se in child psychia ic clinical wo k (7,39,44-46), as was also obse ed in his s udy. Only abou one- hi d o he s udy pa ien s had unde gone a physical e alua ion a SGA ini ia ion. App oxima ely one- i h o he pa ien s medica ed o o e 24 mon hs had no physical examina ion a any o he ollow-up isi s. Fu he mo e, in o ma ion on g ow h his o y was lacking o abou one- hi d o he pa ien s. I is also no ewo hy ha in o ma ion on he child’s amily his o y o soma ic diseases, which is o impo ance when assessing isk ac o s associa ed wi h, o example, me abolic diso de s, was o en incomple e and less ho oughly documen ed han he amily his o y o psychia ic illnesses. E alua ing he bene i s and isks o SGA medica ion among child en is complex. SGA ea men o child en is o en associa ed wi h he symp oma ic ea men o de elopmen al o o he diso de s wi h a long du a ion (1,2,8,14,21,22,25). The a e age du a ion o he SGA medica ion was long in his s udy as well: he median du a ion was almos wo yea s. Mos o he SGA- ea ed pa ien s (81%) in his s udy had an imp o emen in hei symp oms a leas o some ex en , bu symp om con ol seemed a imes insu icien . In many cases, he e was luc ua ion in he symp oms despi e he con inuous medica ion and he possible bene i s gained a he beginning did no emain so e iden in he long un. Du ing he ea ly yea s, biopsychosocial de elopmen is apid, and many aspec s a ec he possible symp om de elopmen . The wo peaks in he SGA ini ia ion age obse ed in his s udy – he i s school yea s and p e-pube y – may bo h e lec imes o inc easing en i onmen al and social demands o he child, and hese imes a e also challenging om a amily pe spec i e. The many o he psycho opic medica ion ials obse ed in his s udy may also ha e in luenced symp om imp o emen o de e io a ion. In 16% o he pa ien s in his s udy, he e ec o he medica ion emained unclea . Despi e his, he medica ion was o en con inued. The use o sys ema ic assessmen me hods o examining changes in pa ien s’ unc ioning o esponse o medica ion was no possible in his s udy due o he sou ce o in o ma ion being pa ien eco ds, which a e o en incomple e and somewha unsys ema ic. Fu he s udies on he subjec a e needed, and sys ema ic assessmen o unc ional capaci y a he baseline and du ing ollow-up should be encou aged. In his s udy, he majo i y o child en medica ed wi h an ipsycho ics had ema kable ad e se li e