Antipsicóticos atípicos para los trastornos de conducta desestabilizantes en niños y jóvenes
Appendices
Appendix 1. Rating scales
Scales for aggression (observer rated)
-
Children’s Aggression Scale – Parent’s version (CAS‐P) (Halperin 2002).
-
Children’s Aggression Scale – Teacher’s version (CAS‐T) (Halperin 2003).
-
Overt Aggression Scale (OAS) (Yudofsky 1986).
-
Modified Overt Aggression scale (MOAS) (Sorgi 1991).
-
Overt Aggression Scale Modified (OAS‐M) (Coccaro 1991).
-
Proactive and Reactive Aggression Scale (PRA) (Dodge 1987).
-
Revised Teacher Rating Scale for Reactive and Proactive Aggression (R‐TRPA) (Brown 1996).
-
Vitiello Aggression Questionnaire (VAQ) (Vitiello 1997).
-
Children's Social Behaviour Scale (CSBS) (Crick 1995).
-
General Behavior Inventory (Parent Version) (P‐GBI) (Youngstrom 2001).
-
Life History of Aggression (LHA) (Coccaro 1997).
Scale for aggression (self‐report)
-
Buss‐Durkee Hostility Inventory (BDHI) (Buss 1957).
-
Aberrant Behaviour Checklist (ABC) – Irritability subscale (Aman 1985a).
-
Child Behaviour Checklist (CBCL) – Aggression subscale (Achenbach 1991).
-
Barratt Aggressive Acts Questionnaire (AAQ) (Barratt 1999).
-
Spielberger Anger and Expression of Anger Inventory (STAXI) (Fuqua 1991).
-
Anger, Irritability, and Aggression Questionnaire (AAIQ) (Coccaro 1991).
-
Buss‐Perry Aggression Questionnaire (B‐PAQ) (Buss 1992).
-
Aggression Questionnaire (AQ) (Vitiello 1990; Malone 1998).
Scales for disruptive behaviour disorders or conduct disorder
-
Nisonger Child Behaviour Rating Form (NCBRF) – Conduct Problem subscale (Aman 1996).
-
Connors' Parent Rating Scale – Revised (CPRS‐R) (Conners 1997a).
-
Conners' Teacher Rating Scale – Revised (CTRS‐R) (Conners 1997a).
-
Swanson, Nolan and Pelham scale, Fourth Edition (SNAP‐IV) (Swanson 1992).
-
Vanderbilt ADHD Diagnostic Parent Rating Scale (VADPRS) (Wolraich 2003).
-
Vanderbilt ADHD Diagnostic Teacher Rating Scale (VADTRS) (Wolraich 1998).
-
Achenbach Child Behavior Checklist (CBCL) (Achenbach 1991).
-
Eyberg Child Behaviour Inventory (ECBI) (Eyberg 1999).
-
New York Teacher Rating Scale for Disruptive and Antisocial Behaviour (NYTRS) (Miller 1995).
-
Home and School Questionnaire (HSQ/SSQ) (Barkley 1997).
-
Antisocial Process Screening Device (APSD) (Frick 2001).
-
Sutter‐Eyberg Student Behavior Inventory Revised (SESBI‐R) (Eyberg 1999).
-
Youth Self Report (YSR) (Achenbach 1991).
-
Conners/Wells' Adolescent Self Report of Symptoms (CASS) – conduct problem and anger control problem subscales (Conners 1997b).
-
Parent Daily report (PDA) (Kazdin 1986).
-
Interview for Antisocial Behaviour (IAB) (Chamberlain 1991).
Appendix 2. Search strategies up to 2011
Cochrane Central Register of Controlled Studies (CENTRAL) in the Cochrane Library, which includes the Cochrane Developmental, Psychosocial and Learning Problems Specialised Register
#1 MeSH descriptor Child Behavior Disorders, this term only
#2 MeSH descriptor Attention Deficit and Disruptive Behavior Disorders, this term only
#3 MeSH descriptor Attention Deficit Disorder with Hyperactivity, this term only
#4 MeSH descriptor Conduct Disorder, this term only
#5 conduct NEAR/5 (disorder* or disturb*)
#6 oppositional*
#7 MeSH descriptor Antisocial Personality Disorder, this term only
#8 (antisocial or anti NEXT social) NEAR/5 (behav* or histor* or conduct*)
#9 attention NEAR/5 deficit*
#10 ad/hd
#11 adhd or "ad/hd" or adhkd or addh or adhs
#12 hyperactiv*
#13 MeSH descriptor Hyperkinesis, this term only
#14 hyperkine*
#15 MeSH descriptor Aggression, this term only
#16 aggress*
#17 MeSH descriptor Agonistic Behavior, this term only
#18 agonistic*
#19 MeSH descriptor Anger, this term only
#20 MeSH descriptor Rage, this term only
#21 anger or angry
#22 malic*
#23hostil*
#24 deceit*
#25 cruel*
#26 MeSH descriptor Juvenile Delinquency, this term only
#27 threaten*
#28 (dangerous* or disrupt* ) NEAR/5 (behav* or histor* or conduct*)
#29 MeSH descriptor Impulsive Behavior, this term only
#30 impulse* or impulsiv*
#31 MeSH descriptor Crime explode all trees
#32 criminal* or violen* or unlawful* or delinquen*
#33 MeSH descriptor Violence, this term only
#34 offend* or offence* or offense*
#35 correctional* or penal*
#36 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35)
#37 MeSH descriptor Clozapine, this term only
#38 MeSH descriptor Risperidone, this term only
#39 risperidon*
#40 clozapin*
#41 amisulprid*
#42 amisulpirid*
#43 aripiprazol*
#44 olanzapin*
#45 quetiapin*
#46 sertindol*
#47 ziprasidon*
#48 zotepin*
#49 atypical NEAR/3 (anti next psychotic* or antipsychotic*)
#50(#37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49)
#51 MeSH descriptor Infant, this term only
#52 MeSH descriptor Child explode all trees
#53 MeSH descriptor Adolescent, this term only
#54 MeSH descriptor Minors, this term only
#55 (child* or boy* or girl* or baby or babies or toddler* or infant* or teen* or adolescen* or juvenile* or preschool* or pre next school* or schoolchild*)
#56 youth* or young* people
#57 young* people
#58 (#51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57)
#59 (#36 AND #50 AND #58)
OVID MEDLINE(R)
1 Child Behavior Disorders/
2 Attention Deficit Disorder with Hyperactivity/
3 "Attention Deficit and Disruptive Behavior Disorders"/
4 Conduct Disorder/
5 (conduct adj5 (disorder$ or disturb$)).mp.
6 oppositional$.mp.
7 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
8 Antisocial Personality Disorder/
9 (attention adj5 deficit$).mp.
10 (adhd or "ad/hd" or adhkd or addh or adhs).tw.
11 hyperactiv$.mp.
12 Hyperkinesis/
13 hyperkine$.mp.
14 Aggression/
15 Agonistic behavior/
16 aggress$.mp.
17 agonistic$.mp.
18 Anger/
19 Rage/
20 (anger or angry).mp.
21 malic$.mp.
22 hostil$.mp.
23 ((dangerous$ or disrupt$ or defiant$) adj3 (behav$ or histor$ or conduct$)).mp.
24 deceit$.mp.
25 cruel$.mp.
26 juvenile delinquency/
27 delinquen$.mp.
28 threaten$.mp.
29 Impulsive Behavior/
30 impulsiv$.mp.
31 impulse$.mp.
32 unlawful$.mp.
33 Violence/
34 violen$.mp.
35 exp Crime/
36 criminal$.mp.
37 penal$.mp.
38 (offend$ or offenc$ or offens$).mp.
39 correctional.mp.
40 or/1‐39
41 amisulprid$.mp.
42 amisulpirid$.mp.
43 aripiprazol$.mp.
44 Clozapine/
45 clozapin$.mp.
46 olanzapin$.mp.
47 quetiapin$.mp.
48 Risperidone/
49 risperidon$.mp.
50 sertindol$.mp.
51 ziprasidon$.mp.
52 zotepin$.mp.
53 (atypical$ adj3 (antipsychotic$ or anti‐psychotic)).mp.
54 or/41‐53
55 (child$ or boy$ or girl$ or baby or babies or toddler$ or infant$ or teen$ or adolescen$ or juvenile$ or preschool$ or pre‐school$ or schoolchild$).mp.
56 (youth$ or young$ people).mp.
57 Child/ or Child, preschool/
58 Infant/
59 Adolescent/
60 Minors/
61 or/55‐60
62 40 and 54 and 61
The search terms "iloperidone" "asenapine", "lurasidone" and "paliperidone" were included in the searches from 2015 onwards to reflect the availablity of new drugs.
Embase Ovid
1 behavior disorder/ or attention deficit disorder/ or disruptive behavior/ or impulse control disorder/ or oppositional defiant disorder/
2 (conduct adj5 (disorder$ or disturb$)).mp.
3 oppositional$.mp.
4 antisocial behavior/
5 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
6 ((antisocial$ or anti‐social$) adj personality adj disorder$).mp.
7 (attention adj5 deficit$).mp.
8 (adhd or "ad/hd" or adhkd or addh or adhs).tw.
9 hyperactiv$.mp.
10 hyperkinesia/
11 hyperkine$.mp.
12 exp aggression/
13 aggress$.mp.
14 agonistic$.mp.
15 (anger or angry).mp.
16 malic$.mp.
17 hostil$.mp.
18 ((dangerous$ or disrupt$) adj3 (behav$ or histor$ or conduct$)).mp.
19 deceit$.mp.
20 cruel$.mp.
21 delinquen$.mp.
22 threaten$.mp.
23 impulsiveness/
24 impulse control disorder/
25 (impulsiv$ or impulse$).mp.
26 unlawful$.mp.
27 exp violence/
28 violen$.mp.
29 exp crime/
30 criminal$.mp.
31 penal$.mp.
32 (offend$ or offenc$ or offens$).mp.
33 correctional.mp.
34 or/1‐33
35 exp atypical antipsychotic agent/
36 amisulprid$.mp.
37 amisulpirid$.mp.
38 aripiprazol$.mp.
39 clozapin$.mp.
40 olanzapin$.mp.
41 quetiapin$.mp.
42 risperidon$.mp.
43 sertindol$.mp.
44 ziprasidon$.mp.
45 zotepin$.mp.
46 (atypical$ adj3 (antipsychotic$ or anti‐psychotic$)).mp.
47 or/35‐46
48 (baby or babies or infant$ or toddler$ or child$ or boy$ or girl$ or preschool$ or pre school$ or teen$ or adolescen$ or juvenile$ or minor$ or youth$ or young people).tw.
49 infant/
50 child/
51 school child/
52 preschool child/
53 adolescent/
54 or/49‐53
55 34 and 47 and 54
PsycINFO strategies
During the preparation of the 2012 review the supplier for PsycINFO changed from EBSCOhost to Ovid . The search stategy was therefore adapted in 2011 for the Ovid platform.
PsycINFO EBSCOhost: 2010 search
S52 S47 and S48 and S51
S51 S49 or S50
S50 baby or babies or infant* or toddler* or child* or boy* or girl* or preschool* or pre school* or schoolchild* or juvenile* or minor* or teen* or adolescen* or youth* or young* people
S49 (ZG "adolescence (13‐17 yrs)") or (ZG "childhood (birth‐12 yrs)") or (ZG "infancy (2‐23 mo)") or (ZG "preschool age (2‐5 yrs)") or (ZG "schoolage (6‐12 yrs)")
S48 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 or S33
S47 S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46
S46 atypical* N3 anti psychotic*
S45 atypical* N3 antipsychotic*
S44 zotepin*
S43 ziprasidon*
S42 sertindol*
S41 risperidon*
S40 quetiapin*
S39 olanzapin*
S38 clozapin*
S37 aripiprazol*
S36 amisulpirid*
S35 amisulprid*
S34 DE "Aripiprazole" or DE "Clozapine" or DE "Olanzapine" or DE "Quetiapine" or DE "Risperidone"
S33 impulsiv* or impulse*
S32 DE "Impulsiveness"
S31 (DE "Violent Crime") or (DE "Violence")
S30 DE "Crime"
S29 DE "Criminal Behavior" OR DE "Juvenile Delinquency"
S28 offend* or offenc* or offens*
S27 violen* or criminal* or penal* or correctional*
S26 unlawful*
S25 threaten*
S24 delinquen*
S23 (disrupt* N3 behav* ) or (disrupt* N3 histor*) or (disrupt* N3 conduct*)
S22 (dangerous* N3 behav* ) or (dangerous* N3 histor*) or (dangerous* N3 conduct*)
S21 cruel*
S20 deceit*
S19 hostil*
S18 malic*
S17 anger or angry or rage*
S16 aggress* or agonistic*
S15 hyperkine*
S14 hyperactiv*
S13 adhd or "ad/hd" or adhkd or addh or adhs
S12 attention N5 deficit*
S11 (anti social* N5 behav*) or (anti social* N5 histor*) or (anti social* N5 conduct*)
S10 (antisocial* N5 behav*) or (antisocial* N5 histor*) or (antisocial* N5 conduct*)
S9 oppositional*
S8 (conduct N5 disturb*)
S7 (conduct N5 disorder*)
S6 DE "Anger" OR DE "Hostility"
S5 (DE "Attention Deficit Disorder with Hyperactivity" or DE "Attention Deficit Disorder" or DE "Hyperkinesis" or DE "Impulsiveness" or DE "Oppositional Defiant Disorder")
S4 DE "Aggressive Behavior" or DE "Aggressiveness"
S3 DE "Conduct Disorder"
S2 DE "Behavior Disorders"
S1 (DE "Antisocial Personality Disorder")
PsycINFO Ovid: 2011 search
1 antisocial behavior/
2 Antisocial Personality Disorder/
3 Behavior Disorders/
4 Conduct Disorder/
5 Aggressive Behavior/
6 Aggressiveness/
7 Impulsiveness/
8 Oppositional Defiant Disorder/
9 exp attention deficit disorder/
10 Hyperkinesis/
11 Anger/
12 Hostility/
13 (conduct adj5 (disorder$ or disturb$)).mp.
14 oppositional$.mp.
15 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
16 (attention adj5 deficit$).mp.
17 (adhd or "ad/hd" or adhkd or addh or adhs).tw.
18 hyperactiv$.mp.
19 hyperkine$.mp.
20 aggress$.mp.
21 agonistic$.mp.
22 (anger or angry).mp.
23 malic$.mp.
24 hostil$.mp.
25 ((dangerous$ or disrupt$ or defiant$) adj3 (behav$ or histor$ or conduct$)).mp.
26 deceit$.mp.
27 cruel$.mp.
28 Juvenile Delinquency/
29 delinquen$.mp.
30 threaten$.mp.
31 impulsiv$.mp.
32 impulse$.mp.
33 unlawful$.mp.
34 Violence/
35 violen$.mp.
36 exp Crime/
37 criminal$.mp.
38 penal$.mp.
39 (offend$ or offenc$ or offens$).mp.
40 correctional.mp.
41 or/1‐40
42 Clozapine/
43 clozapin$.mp.
44 exp Olanzapine/
45 olanzapin$.mp.
46 Quetiapine/
47 quetiapin$.mp.
48 Risperidone/
49 risperidon$.mp.
50 sertindol$.mp.
51 ziprasidon$.mp.
52 zotepin$.mp.
53 amisulprid$.mp.
54 amisulpirid$.mp.
55 aripiprazole/
56 aripiprazol$.mp.
57 (atypical$ adj3 (antipsychotic$ or anti‐psychotic$)).mp.
58 or/42‐57
59 (child$ or boy$ or girl$ or baby or babies or toddler$ or infant$ or teen$ or adolescen$ or juvenile$ or preschool$ or pre‐school$ or schoolchild$).mp.
60 (youth$ or young$ people).mp.
61 ("100" or "120" or "140" or "160" or "180" or "200" or "320").ag.
62 59 or 60 or 61
63 41 and 58 and 62
CINAHL EBSCOhost (Cumulative Index to Nursing and Allied Health Literature)
S53 S33 and S47 and S52
S52 (S48 or S49 or S50 or S51)
S51 AG preschool
S50 AG adolescent
S49 AG child
S48 baby or babies or infant* or toddler* or child* or boy* or girl* or preschool* or pre school* or schoolchild* or juvenile* or minor* or teen* or adolescen* or youth* or young* people
S47 S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46
S46 atypical* N3 anti psychotic*
S45 atypical* N3 antipsychotic*
S44 zotepin*
S43 ziprasidon*
S42 sertindol*
S41 risperidon*
S40 quetiapin*
S39 olanzapin*
S38 clozapin*
S37 aripiprazol*
S36 amisulpirid*
S35 amisulprid*
S34 (MH "Aripiprazole") or (MH "Clozapine") or (MH "Olanzapine") or (MH "Quetiapine") or (MH "Risperidone")
S33 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32
S32 impulse* or impulsiv*
S31 (MH "Impulse Control Disorders")
S30 (MH "Violence") or (MH "School Violence") or (MH "Sibling Violence")
S29 (MH "Juvenile Delinquency") or (MH "Juvenile Offenders+")
S28 (MH "Crime")
S27 (MH "Public Offenders")
S26 offend* or offenc* or offens*
S25 violen* or criminal* or penal* or correctional* or unlawful* or threaten*
S24 delinquen*
S23 (disrupt* N3 behav* ) or (disrupt* N3 histor*) or (disrupt* N3 conduct*)
S22 (dangerous* N3 behav* ) or (dangerous* N3 histor*) or (dangerous* N3 conduct*)
S21 cruel*
S20 deceit*
S19 hostil*
S18 malic*
S17 anger or angry or rage*
S16 aggress* or agonistic*
S15 hyperkine*
S14 hyperactiv*
S13 adhd or "ad/hd" or adhkd or addh or adhs
S12 attention N5 deficit*
S11 (anti social* N5 behav*) or (anti social* N5 histor*) or (anti social* N5 conduct*)
S10 (antisocial* N5 behav*) or (antisocial* N5 histor*) or (antisocial* N5 conduct*)
S9 oppositional*
S8 (conduct N5 disorder*) OR (conduct N5 disturb*)
S7 (MH "Anger")
S6 (MH "Aggression")
S5 (MH "Hyperkinesis")
S4 (MH "Disruptive Behavior")
S3 (MH "Antisocial Personality Disorder")
S2 (MH "Attention Deficit Hyperactivity Disorder")
S1 (MH "Child Behavior Disorders")
ClinicalTrials.gov
adhd OR dispruptive OR oppositional OR conduct OR impulsive OR anger OR rage OR antisocial | aripiprazole OR olanzapine OR quetiapine OR sertindole OR ziprasidone OR zotepine OR clozapine OR risperidone OR amisulpride OR amisulpirid | Child, Adult |
CenterWatch
Advanced search: (amisulpride or amisulpiride or aripiprazole or clozapine or olanzapine or quetiapine or risperidone or sertindole or ziprasidone or zotepine ) AND (adhd or disruptive or oppositional or "conduct disorder" or impulsive or anger or rage or antisocial
WHO ICTRP
Intervention| aripiprazole OR olanzapine OR quetiapine OR sertindole OR ziprasidone OR zotepine OR clozapine OR risperidone OR amisulpride OR amisulpiride
metaRegister of Controlled Trials
antipsychotic* AND child* AND behav*
UK Clinical Research Network (UKCRN)
atypical antipsychotics
Appendix 3. Search strategies from 2011 onwards
CENTRAL, in the Cochrane Library, which includes the Cochrane Developmental, Psychosocial and Learning Problems Specialised Register
#1MeSH descriptor: [Child Behavior Disorders] this term only
#2MeSH descriptor: [Attention Deficit and Disruptive Behavior Disorders] this term only
#3MeSH descriptor: [Attention Deficit Disorder with Hyperactivity] this term only
#4MeSH descriptor: [Conduct Disorder] this term only
#5(conduct near/5 (disorder* or disturb*))
#6oppositional*
#7MeSH descriptor: [Antisocial Personality Disorder] this term only
#8((antisocial or anti next social) near/5 (behav* or histor* or conduct*))
#9(attention near/5 deficit*)
#10(adhd or "ad/hd" or adhkd or addh or adhs)
#11hyperactiv* or hyper next activ*
#12hyperkine* or hyper next kin*
#13aggress*
#14agonistic*
#15MeSH descriptor: [Anger] this term only
#16MeSH descriptor: [Rage] this term only
#17(anger or angry)
#18anger or angry
#19malic*
#20hostil*
#21deceit*
#22cruel*
#23(dangerous* or disrupt*) near/5 (behav* or histor* or conduct*)
#24MeSH descriptor: [Impulsive Behavior] this term only
#25impulse* or impulsiv*
#26MeSH descriptor: [Crime] explode all trees
#27criminal* or violen* or unlawful* or delinquen*
#28MeSH descriptor: [Violence] this term only
#29offend* or offence* or offense*
#30correctional* or penal*
#31(offend* or offenc* or offens*)
#32{or #1‐#31}
#33MeSH descriptor: [Risperidone] this term only
#34MeSH descriptor: [Clozapine] this term only
#35amisulpirid*
#36amisulprid*
#37aripiprazol*
#38asenapin*
#39clozapin*
#40iloperidon*
#41lurasidon*
#42olanzapin*
#43paliperid*
#44quetiapin*
#45risperidon*
#46sertindol*
#47ziprasidon*
#48zotepin*
#49atypical near/3 (anti next psychotic* or antipsychotic*)
#50{or #33‐#49}
#51MeSH descriptor: [Infant] this term only
#52MeSH descriptor: [Child] explode all trees
#53MeSH descriptor: [Adolescent] this term only
#54MeSH descriptor: [Minors] this term only
#55(child* or boy* or girl* or baby or babies or toddler* or infant* or teen* or adolescen* or juvenile* or preschool* or pre next school* or schoolchild*)
#56youth* or young* people
#57{or #51‐#56}
#58#32 and #50 and #57
Ovid MEDLINE(R)
1 Child Behavior Disorders/
2 Attention Deficit Disorder with Hyperactivity/
3 "Attention Deficit and Disruptive Behavior Disorders"/
4 Conduct Disorder/
5 (conduct adj5 (disorder$ or disturb$)).mp.
6 oppositional$.mp.
7 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
8 Antisocial Personality Disorder/
9 (attention adj5 deficit$).mp.
10 (adhd or "ad/hd" or adhkd or addh or adhs).tw.
11 hyperactiv$.mp.
12 Hyperkinesis/
13 hyperkine$.mp.
14 Aggression/
15 Agonistic behavior/
16 aggress$.mp.
17 agonistic$.mp.
18 Anger/
19 Rage/
20 (anger or angry).mp.
21 malic$.mp.
22 hostil$.mp.
23 ((dangerous$ or disrupt$ or defiant$) adj3 (behav$ or histor$ or conduct$)).mp.
24 deceit$.mp.
25 cruel$.mp.
26 delinquen$.mp.
27 threaten$.mp.
28 Impulsive Behavior/
29 impulsiv$.mp.
30 impulse$.mp.
31 unlawful$.mp.
32 Violence/
33 violen$.mp.
34 Crime/
35 criminal$.mp.
36 penal$.mp.
37 (offend$ or offenc$ or offens$).mp.
38 correctional.mp.
39 or/1‐38
40 amisulprid$.mp.
41 amisulpirid$.mp.
42 aripiprazol$.mp.
43 asenapin$.mp.
44 Clozapine/
45 clozapin$.mp.
46 iloperidon$.mp.
47 lurasidon$.mp.
48 olanzapin$.mp.
49 paliperidon$.mp.
50 quetiapin$.mp.
51 Risperidone/
52 risperidon$.mp.
53 sertindol$.mp.
54 ziprasidon$.mp.
55 zotepin$.mp.
56 (atypical$ adj3 (antipsychotic$ or anti‐psychotic)).mp.
57 or/40‐56
58 (child$ or boy$ or girl$ or baby or babies or toddler$ or infant$ or teen$ or adolescen$ or juvenile$ or preschool$ or pre‐school$ or schoolchild$).mp.
59 (youth$ or young$ people).mp.
60 Child/ or Child, preschool/
61 Infant/
62 Adolescent/
63 Minors/
64 or/58‐63
65 39 and 57 and 64
Ovid MEDLINE(R) In‐Process & Other Non‐Indexed Citations
1 (conduct adj5 (disorder$ or disturb$)).mp.
2 oppositional$.mp.
3 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
4 (attention adj5 deficit$).mp.
5 (adhd or "ad/hd" or adhkd or addh or adhs).mp.
6 hyperactiv$.mp.
7 hyperkine$.mp.
8 aggress$.mp.
9 agonistic$.mp.
10 (anger or angry).mp.
11 malic$.mp.
12 hostil$.mp.
13 ((dangerous$ or disrupt$ or defiant$) adj3 (behav$ or histor$ or conduct$)).mp.
14 deceit$.mp.
15 cruel$.mp.
16 delinquen$.mp.
17 threaten$.mp.
18 impulsiv$.mp.
19 impulse$.mp.
20 unlawful$.mp.
21 violen$.mp.
22 criminal$.mp.
23 penal$.mp.
24 (offend$ or offenc$ or offens$).mp.
25 correctional.mp.
26 amisulprid$.mp.
27 amisulpirid$.mp.
28 aripiprazol$.mp.
29 asenapin$.mp.
30 clozapin$.mp.
31 iloperidon$.mp.
32 lurasidone.mp.
33 olanzapin$.mp.
34 paliperid$.mp.
35 quetiapin$.mp.
36 risperidon$.mp.
37 sertindol$.mp.
38 ziprasidon$.mp.
39 zotepin$.mp.
40 (atypical$ adj3 (antipsychotic$ or anti‐psychotic)).mp.
41 (child$ or boy$ or girl$ or baby or babies or toddler$ or infant$ or teen$ or adolescen$ or juvenile$ or preschool$ or pre‐school$ or schoolchild$).mp.
42 (youth$ or young$ people).mp.
43 or/1‐25
44 or/26‐40
45 or/41‐42
46 43 and 44 and 45
Embase Ovid
1 behavior disorder/ or attention deficit disorder/ or disruptive behavior/ or impulse control disorder/ or oppositional defiant disorder/
2 (conduct adj5 (disorder$ or disturb$)).mp.
3 oppositional$.mp.
4 antisocial behavior/
5 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
6 ((antisocial$ or anti‐social$) adj personality adj disorder$).mp.
7 (attention adj5 deficit$).mp.
8 (adhd or "ad/hd" or adhkd or addh or adhs).tw.
9 hyperactiv$.mp.
10 hyperkinesia/
11 hyperkine$.mp.
12 exp aggression/
13 aggress$.mp.
14 agonistic$.mp.
15 (anger or angry).mp.
16 malic$.mp.
17 hostil$.mp.
18 ((dangerous$ or disrupt$) adj3 (behav$ or histor$ or conduct$)).mp.
19 deceit$.mp.
20 cruel$.mp.
21 delinquen$.mp.
22 threaten$.mp.
23 impulsiveness/
24 impulse control disorder/
25 (impulsiv$ or impulse$).mp.
26 unlawful$.mp.
27 exp violence/
28 violen$.mp.
29 exp crime/
30 criminal$.mp.
31 penal$.mp.
32 (offend$ or offenc$ or offens$).mp.
33 correctional.mp.
34 or/1‐33
35 exp atypical antipsychotic agent/
36 amisulprid$.mp.
37 amisulpirid$.mp.
38 aripiprazol$.mp.
39 asenapin$.mp.
40 clozapin$.mp.
41 iloperidon$.mp.
42 lurasidone.mp.
43 olanzapin$.mp.
44 paliperid$.mp.
45 quetiapin$.mp.
46 risperidon$.mp.
47 sertindol$.mp.
48 ziprasidon$.mp.
49 zotepin$.mp.
50 (atypical$ adj3 (antipsychotic$ or anti‐psychotic$)).mp.
51 or/35‐50
52 (baby or babies or infant$ or toddler$ or child$ or boy$ or girl$ or preschool$ or pre school$ or teen$ or adolescen$ or juvenile$ or minor$ or youth$ or young people).tw.
53 infant/
54 child/
55 school child/
56 preschool child/
57 adolescent/
58 or/53‐57
59 34 and 51 and 58
PsycINFO Ovid
1 antisocial behavior/
2 Antisocial Personality Disorder/
3 Behavior Disorders/
4 Conduct Disorder/
5 Aggressive Behavior/
6 Aggressiveness/
7 Impulsiveness/
8 Oppositional Defiant Disorder/
9 exp attention deficit disorder/
10 Hyperkinesis/
11 Anger/
12 Hostility/
13 (conduct adj5 (disorder$ or disturb$)).mp.
14 oppositional$.mp.
15 ((antisocial$ or anti‐social$) adj5 (behav$ or histor$ or conduct)).mp.
16 (attention adj5 deficit$).mp.
17 (adhd or "ad/hd" or adhkd or addh or adhs).tw.
18 hyperactiv$.mp.
19 hyperkine$.mp.
20 aggress$.mp.
21 agonistic$.mp.
22 (anger or angry).mp.
23 malic$.mp.
24 hostil$.mp.
25 ((dangerous$ or disrupt$ or defiant$) adj3 (behav$ or histor$ or conduct$)).mp.
26 deceit$.mp.
27 cruel$.mp.
28 Juvenile Delinquency/
29 delinquen$.mp.
30 threaten$.mp.
31 impulsiv$.mp.
32 impulse$.mp.
33 unlawful$.mp.
34 Violence/
35 violen$.mp.
36 exp Crime/
37 criminal$.mp.
38 penal$.mp.
39 (offend$ or offenc$ or offens$).mp.
40 correctional.mp.
41 or/1‐40
42 Clozapine/
43 clozapin$.mp.
44 exp Olanzapine/
45 olanzapin$.mp.
46 Quetiapine/
47 quetiapin$.mp.
48 Risperidone/
49 risperidon$.mp.
50 sertindol$.mp.
51 ziprasidon$.mp.
52 zotepin$.mp.
53 amisulprid$.mp.
54 amisulpirid$.mp.
55 aripiprazole/
56 aripiprazol$.mp.
57 asenapin$.mp.
58 iloperidon$.mp.
59 lurasidone.mp.
60 paliperid$.mp.
61 (atypical$ adj3 (antipsychotic$ or anti‐psychotic)).mp.
62 or/42‐61
63 (child$ or boy$ or girl$ or baby or babies or toddler$ or infant$ or teen$ or adolescen$ or juvenile$ or preschool$ or pre‐school$ or schoolchild$).mp. (829362)
64 (youth$ or young$ people).mp. (94048)
65 ("100" or "120" or "140" or "160" or "180" or "200" or "320").ag.
66 63 or 64 or 65 )
67 41 and 62 and 66
CINAHL Plus EBSCOhost (Cumulative Index to Nursing and Allied Health Literature)
S1 (MH "Child Behavior Disorders")
S2 (MH "Attention Deficit Hyperactivity Disorder")
S3 (MH "Antisocial Personality Disorder")
S4 (MH "Disruptive Behavior")
S5 (MH "Hyperkinesis")
S6 (MH "Aggression")
S7 (MH "Anger")
S8 (conduct N5 disorder*) OR (conduct N5 disturb*)
S9 oppositional*
S10 (antisocial* N5 behav*) or (antisocial* N5 histor*) or (antisocial* N5 conduct*)
S11 (anti social* N5 behav*) or (anti social* N5 histor*) or (anti social* N5 conduct*)
S12 attention N5 deficit*
S13 adhd or "ad/hd" or adhkd or addh or adhs
S14 hyperactiv*
S15 hyperkine*
S16 aggress* or agonistic*
S17 anger or angry or rage*
S18 malic* or hostil*
S19 deceit*
S20 cruel*
S21 (dangerous* N3 behav* ) or (dangerous* N3 histor*) or (dangerous* N3 conduct*)
S22 (disrupt* N3 behav* ) or (disrupt* N3 histor*) or (disrupt* conduct*)
S23 delinquen*
S24 violen* or criminal* or penal* or correctional* or unlawful* or threaten*
S25 offend* or offenc* or offens*
S26 (MH "Public Offenders")
S27 (MH "Crime")
S28 (MH "Juvenile Delinquency") or (MH "Juvenile Offenders+")
S29 (MH "Violence") or (MH "School Violence") or (MH "Sibling Violence")
S30 (MH "Impulse Control Disorders")
S31 impulse* or impulsiv*
S32 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31
S33 (MH "Aripiprazole") or (MH "Clozapine") or (MH "Olanzapine") or (MH "Quetiapine") or (MH "Risperidone")
S34 (MH "Asenapine")
S35 (MH "Iloperidone")
S36 (MH "Paliperidone")
S37 amisulpirid*
S38 amisulprid*
S39 aripiprazol*
S40 asenapin*
S41 clozapin*
S42 iloperidon*
S43 lurasidon*
S44 olanzapin*
S45 paliperid*
S46 quetiapin*
S47 risperidon*
S48 sertindol*
S49 ziprasidon*
S50 zotepin*
S51 (atypical n3 (antipsychotic* or anti‐psychotic*))
S52S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51
S53 S32 AND S52
S54 baby or babies or infant* or toddler* or child* or boy* or girl* or preschool* or pre school* or schoolchild* or juvenile* or minor* or teen* or adolescen* or youth* or young* people
S55 AG child
S56 AG adolescent
S57 AG preschool
S58 S54 OR S55 OR S56 OR S57
S59 S53 AND S58
Cochrane Database of Systematic Reviews (CDSR) in the Cochrane Library
#1 MeSH descriptor: [Child Behavior Disorders] this term only
#2 MeSH descriptor: [Attention Deficit and Disruptive Behavior Disorders] this term only
#3 MeSH descriptor: [Attention Deficit Disorder with Hyperactivity] this term only
#4 MeSH descriptor: [Conduct Disorder] this term only
#5 (conduct near/5 (disorder* or disturb*)):ti,ab,kw
#6 (oppositional*):ti,ab,kw
#7 MeSH descriptor: [Antisocial Personality Disorder] this term only
#8 ((antisocial or anti next social) near/5 (behav* or histor* or conduct*)):ti,ab,kw
#9 (attention near/5 deficit*):ti,ab,kw
#10 (adhd or "ad/hd" or adhkd or addh or adhs):ti,ab,kw
#11 hyperactiv*:ti,ab,kw
#12 hyperkine*:ti,ab,kw
#13 aggress*:ti,ab,kw
#14 agonistic*:ti,ab,kw
#15 MeSH descriptor: [Anger] this term only
#16 MeSH descriptor: [Rage] this term only
#17(anger or angry):ti,ab,kw
#18 malic*:ti,ab,kw
#19 hostil*:ti,ab,kw
#20 deceit*:ti,ab,kw
#21 cruel*:ti,ab,kw
#22 ((dangerous* or disrupt*) near/5 (behav* or histor* or conduct*)):ti,ab,kw
#23 MeSH descriptor: [Impulsive Behavior] this term only
#24 (impulse* or impulsiv*):ti,ab,kw
#25 MeSH descriptor: [Crime] explode all trees
#26 (criminal* or violen* or unlawful* or delinquen*):ti,ab,kw
#27 MeSH descriptor: [Violence] this term only
#28 (offend* or offence* or offens*):ti,ab,kw
#29 (correctional* or penal*):ti,ab,kw
#30 {or #1‐#29}
#31 MeSH descriptor: [Risperidone] this term only
#32 MeSH descriptor: [Clozapine] this term only
#33 amisulpirid*:ti,ab,kw
#34 amisulprid*:ti,ab,kw
#35 aripiprazol*:ti,ab,kw
#36 asenapin*:ti,ab,kw
#37 clozapin*:ti,ab,kw
#38 iloperidon*:ti,ab,kw
#39 lurasidon*:ti,ab,kw
#40 olanzapin*:ti,ab,kw
#41 paliperid*:ti,ab,kw
#42 quetiapin*:ti,ab,kw
#43 risperidon*:ti,ab,kw
#44 sertindol*:ti,ab,kw
#45 ziprasidon*:ti,ab,kw
#46 zotepin*:ti,ab,kw
#47 (atypical near/3 (anti next psychotic* or antipsychotic*)):ti,ab,kw
#48 {or #31‐#47}
#49 MeSH descriptor: [Infant] this term only
#50 MeSH descriptor: [Child] explode all trees
#51 MeSH descriptor: [Adolescent] this term only
#52 MeSH descriptor: [Minors] this term only
#53 (child* or boy* or girl* or baby or babies or toddler* or infant* or teen* or adolescen* or juvenile* or preschool* or pre next school* or schoolchild*):ti,ab,kw
#54 (youth* or young* next people):ti,ab,kw
#55 {or #49‐#54}
#56#48 and #55 and #30
Database of Abstracts of Reviews of Effects (DARE) in the Cochrane Library
#1 MeSH descriptor: [Child Behavior Disorders] this term only
#2 MeSH descriptor: [Attention Deficit and Disruptive Behavior Disorders] this term only
#3 MeSH descriptor: [Attention Deficit Disorder with Hyperactivity] this term only
#4 MeSH descriptor: [Conduct Disorder] this term only
#5 (conduct near/5 (disorder* or disturb*)):ti,ab,kw
#6 (oppositional*):ti,ab,kw
#7 MeSH descriptor: [Antisocial Personality Disorder] this term only
#8 ((antisocial or anti next social) near/5 (behav* or histor* or conduct*)):ti,ab,kw
#9 (attention near/5 deficit*):ti,ab,kw
#10 (adhd or "ad/hd" or adhkd or addh or adhs):ti,ab,kw
#11 hyperactiv*:ti,ab,kw
#12 hyperkine*:ti,ab,kw
#13 aggress*:ti,ab,kw
#14 agonistic*:ti,ab,kw
#15 MeSH descriptor: [Anger] this term only
#16 MeSH descriptor: [Rage] this term only
#17(anger or angry):ti,ab,kw
#18 malic*:ti,ab,kw
#19 hostil*:ti,ab,kw
#20 deceit*:ti,ab,kw
#21 cruel*:ti,ab,kw
#22 ((dangerous* or disrupt*) near/5 (behav* or histor* or conduct*)):ti,ab,kw
#23 MeSH descriptor: [Impulsive Behavior] this term only
#24 (impulse* or impulsiv*):ti,ab,kw
#25 MeSH descriptor: [Crime] explode all trees
#26 (criminal* or violen* or unlawful* or delinquen*):ti,ab,kw
#27 MeSH descriptor: [Violence] this term only
#28 (offend* or offence* or offens*):ti,ab,kw
#29 (correctional* or penal*):ti,ab,kw
#30 {or #1‐#29}
#31 MeSH descriptor: [Risperidone] this term only
#32 MeSH descriptor: [Clozapine] this term only
#33 amisulpirid*:ti,ab,kw
#34 amisulprid*:ti,ab,kw
#35 aripiprazol*:ti,ab,kw
#36 asenapin*:ti,ab,kw
#37 clozapin*:ti,ab,kw
#38 iloperidon*:ti,ab,kw
#39 lurasidon*:ti,ab,kw
#40 olanzapin*:ti,ab,kw
#41 paliperid*:ti,ab,kw
#42 quetiapin*:ti,ab,kw
#43 risperidon*:ti,ab,kw
#44 sertindol*:ti,ab,kw
#45 ziprasidon*:ti,ab,kw
#46 zotepin*:ti,ab,kw
#47 (atypical near/3 (anti next psychotic* or antipsychotic*)):ti,ab,kw
#48 {or #31‐#47}
#49 MeSH descriptor: [Infant] this term only
#50 MeSH descriptor: [Child] explode all trees
#51 MeSH descriptor: [Adolescent] this term only
#52 MeSH descriptor: [Minors] this term only
#53 (child* or boy* or girl* or baby or babies or toddler* or infant* or teen* or adolescen* or juvenile* or preschool* or pre next school* or schoolchild*):ti,ab,kw
#54 (youth* or young* next people):ti,ab,kw
#55 {or #49‐#54}
#56#48 and #55 and #30
ClinicalTrials.gov
Interventional Studies | antisocial OR disruptive OR conduct OR oppositional OR attention deficit OR adhd | aripiprazole OR olanzapine OR quetiapine OR sertindole OR ziprasidone OR zotepine OR clozapine OR risperidone OR amisulpride OR amisulpirid OR asenapine OR iloperidone OR lurasidone OR paliperidone OR atypical | Child |
WHO ICTRP
Condition: antisocial OR disruptive OR conduct OR oppositional OR attention OR adhd AND Intervention: aripiprazole OR olanzapine OR quetiapine OR sertindole OR ziprasidone OR zotepine OR clozapine OR risperidone OR amisulpride OR amisulpirid OR asenapine OR iloperidone OR lurasidone OR paliperidone OR atypical AND Clinical Trials in children= selected AND Recruitment status =all
Appendix 4. Search summary 2011 onwards
| Database | Search date | Database date range or issue | Number of records | Limits applied |
| Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library and which includes the Cochrane Developmental, Psychosocial and Learning Problems Specialised Register | 26 January 2015 | 2014, Issue 12 (December) | 42 | Limited to 2011‐2015 and new drugs for all years |
| 17 February 2016 | 2016, Issue 1 | 12 | Limited to 2015‐2016 | |
| 19 January 2017 | 2016, Issue 11 | 19 | Limited to 2015‐2017 and de‐duped with previous records | |
| Ovid MEDLINE | 23 January 2015 | 1946 to January Week 3 2015 | 158 | ED=20110801‐20150123 and new drugs for all years |
| 17 February 2016 | 1946 to February Week 1 2016 | 47 | ED=20150101‐20160204 | |
| 19 January 2017 | 1946 to December Week 1 2016 | 52 | ED=20150101‐20161114 and de‐duped with previous records | |
| Ovid MEDLINE(R) In‐Process & Other Non‐Indexed Citations | 23 January 2015 | 22 January 2015 | 56 | No limits |
| 17 February 2016 | 16 February 2016 | 70 | No limits | |
| 19 January 2017 | 18 January 2017 | 53 | De‐dupedlicated with previous records | |
| Embase Ovid | 28 January 2015 | 1980 to 2015 Week 03 | 721 | 2011 to current and new drugs for all years |
| 17 February 2016 | 1980 to 2016 Week 07 | 311 | 2015 to current | |
| 19 January 2017 | 1980 to 2017 Week 03 | 240 | 2015 to current. De‐duped with previous records | |
| PsycINFO Ovid | 23 January 2015 | 1806 to January Week 3 2015 | 245 | UP=20110801‐20150115 and new drugs for all years |
| 17 February 2016 | 1806 to February Week 1 2016 | 67 | UP=20150115‐20160201 | |
| 19 January 2017 | 1806 to January Week 2 2017 | 60 | UP=20150115‐20170109 de‐duped with previous records | |
| CINAHL Plus EBSCO (Cumulative Index to Nursing and Allied Health Literature) | 27 January 2015 | 1937 to current | 73 | EM = 2011801 onwards plus new drugs for all years |
| 17 February 2016 | 1937 to current | 29 | EM = 20150101 onwards | |
| 19 January 2017 | 1937 to current | 17 | EM 20150101onwards . De‐duped with previous records | |
| Cochrane Database of Systematic Reviews (CDSR), part of the Cochrane Library | 26 January 2015 | 1 of 12 2015 | 5 | No date limits. Not searched in 2011 |
| 17 February 2016 | 2016 Issue 2 (February) | 0 | 2015‐2016 | |
| 19 January 2017 | 2017, Issue 1 (January) | 1 | 2016‐2017 | |
| Database of Abstracts of Reviews of Effect (DARE), part of the Cochrane Library | 26 January 2015 | 2014 Issue 4 (October) | 5 | No date limits; not searched previously |
| 17 February 2016 | 2015 Issue 2 (April) | 0 | 2014‐2015. Not searched in later years because there is no new content after 2015 Issue 2 | |
| ClinicalTrials.gov (clinicaltrials.gov) | 26 January 2015 | All available years | 6 | Limited to trials registered since 1 August 2011 |
| 18 February 2016 | All available years | 42 | No limits | |
| 20 January 2017 | All available years | 12 | Limited to trials received from 18 February 2016 to 20 January 2017 | |
| World Health Organisation International Clinical Trials Registry Platform (WHO ICTRP;apps.who.int/trialsearch) | 27 January 2015 | All available years | 8 | Limited to trials registered since 1 August 2011 |
| 18 February 2016 | All available years | 32 | No limits | |
| 20 January 2017 | All available years | 7 | Limited to trials registered since 18 February 2017 | |
| Total records | 2390 | |||
study flow diagram
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Risperidone versus placebo, Outcome 1 Aggression: ABC irritability (mean change scores).
Comparison 1 Risperidone versus placebo, Outcome 2 Aggression: OAS‐M, ABS Reactive subscale (final scores).
Comparison 1 Risperidone versus placebo, Outcome 3 Aggression: OAS‐M, ABS Proactive subscale (final scores).
Comparison 1 Risperidone versus placebo, Outcome 4 Conduct: NCBR‐CP (mean change scores).
Comparison 1 Risperidone versus placebo, Outcome 5 Weight gain (antipsychotic only): Kg (mean change scores).
Comparison 1 Risperidone versus placebo, Outcome 6 Weight gain (antipsychotic and stimulant): Kg (mean change scores).
| Risperidone compared to placebo for disruptive behaviours in children and youths | ||||||
| Patient or population: Disruptive behaviours in children and youths | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
| Risk with placebo | Risk with risperidone | |||||
| Aggression | The mean aggression ABC‐I score ranged across control groups from −4.40 to 0.10 | The mean aggression ABC‐I score in the intervention groups was, on average, 6.49 lower (8.79 lower to 4.19 lower) | ‐ | 238 | ⊕⊕⊝⊝ | Included studies: Aman 2002; Snyder 2002; Van Bellinghen 2001 |
| Aggression | The mean aggression OAS‐M and ABS Proactive score ranged across control groups from 8.10 to 15.10 | The mean aggression OAS‐M and ABS Proactive score in the intervention groups was, on average, 1.12 lower (2.30 lower to 0.06 higher) | ‐ | 190 | ⊕⊕⊕⊝ | Included studies: Buitelaar 2001; TOSCA study |
| Conduct | The mean conduct score ranged across control groups from −6.20 to 25.80 | The mean conduct score in the intervention groups was, on average, 8.61 lower (11.49 lower to 5.74 lower) | ‐ | 225 | ⊕⊕⊕⊝ | Included studies: Aman 2002; Snyder 2002 |
| Weight gain (treatment with antipsychotic only) | The mean weight gain (treatment with antipsychotic only) score in the control groups ranged from 0.74 to 0.90 | The mean weight gain score in the intervention groups was, on average, 2.37 higher (0.26 higher to 4.49 higher) | ‐ | 138 | ⊕⊕⊕⊝ | Included studies: Aman 2002; Findling 2000 |
| Weight gain (treatment with antipsychotic and stimulant) | The mean weight gain (treatment with antipsychotic and stimulant) score in the control groups ranged from −1.20 to 0.90 | The mean weight gain score in the intervention groups was, on average, 2.14 higher (1.04 higher to 3.23 higher) | ‐ | 305 | ⊕⊕⊝⊝ | Included studies: Aman 2002; Findling 2000; TOSCA study |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ABS: Antisocial Behavior Scale;CI: Confidence interval; MD: Mean difference;OAS: Overt Aggression Scale;OAS‐M: Overt Aggression Scale ‒ Modified; RCT: Randomised controlled trial; SMD: Standardized mean difference | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels because of unclear risk of bias due to lack of information on selection bias and detection bias in 2 studies, and unclear risk of bias due to lack of information and poor reporting standards in 1 study. 2 trials assessed outpatients, 1 trial assessed patients in residential care. 2 Unclear allocation concealment and unclear blinding of outcome assessment for 1 study and potential reporting bias in both studies. 3 Downgraded 1 level because of unclear allocation concealment and unclear blinding of outcome assessment for both studies and unclear attrition and potential reporting bias. 4 Downgraded 1 level because of unclear blinding of outcome assessment and potential reporting bias. Heterogeneity: Tau² = 2.22; Chi² = 20.77, df = 1 (P < 0.00001); I² = 95%. 5 Downgraded 2 levels because of unclear blinding of outcome assessment in 2 studies, potential reporting bias in 3 studies, and potential attrition bias in 2 studies. Heterogeneity: Tau² = 0.85; Chi² = 23.32, df = 2 (P < 0.00001); I² = 91%. | ||||||
| Analysis | Method |
| Measures of treatment effect | For dichotomous data, we planned to analyse data on the intention‐to‐treat principle with dropouts included in the analysis. Out of the 10 studies, 1 used dichotomous outcomes (Armenteros 2007), therefore we were not able to perform further analyses. |
| Unit of analysis issues | For cross‐over trials, we planned to do paired analysis if data were presented. Otherwise, we planned to take all measurements from intervention periods and all measurements from control periods and analyse these as if the trial was a parallel‐group trial, acknowledging that there might be unit of analysis errors that could underestimate the precision of the estimate of the treatment effect (Deeks 2011). However, no cross‐over trials were identified. Also, there were no cluster‐randomised controlled trials, so we did not have to take this into account in our analyses. |
| Dealing with missing data ‒ missing participants | We intended to calculate the best‐ and worst‐case scenarios for the clinical response outcome, if possible. For example, the best‐case scenario assumed that dropouts in the intervention group had positive outcomes and those in the control group had negative outcomes. In the worst‐case scenario, dropouts in the intervention group had negative outcomes and those in the control group had positive outcomes. |
| Assessment of heterogeneity | Chapter 9 in the Cochrane Handbook recommends using a range for I² and a guide to interpretation (Deeks 2011). Had we found either moderate heterogeneity (I² in the range of 30% to 60%) or substantial heterogeneity (I² in the range of 50% to 90%), as specified in our protocol (Loy 2010), we planned to examine it using specified subgroup and sensitivity analyses (see Subgroup analysis and investigation of heterogeneity and Sensitivity analysis). |
| Assessment of reporting bias | We intended to draw funnel plots (effect size versus standard error) to assess publication bias if sufficient studies were found. Asymmetry of the plots may indicate publication bias, although they may also represent a true relationship between trial size and effect size. If such a relationship were identified, we planned to examine the clinical diversity of the studies as a possible explanation (Egger 1997). There were insufficient studies in our meta‐analysis to perform a funnel plot. |
| Subgroup analysis and investigation of heterogeneity | It was our intention to conduct separate analyses on the following subgroups, where possible.
There were too few studies in any of the analyses for us to carry out any subgroup analyses. |
| Sensitivity analysis | We intended to perform sensitivity analyses to explore whether the results of the review were robust in relation to certain study characteristics. We intended to exclude trials with 'no' or 'unclear' ratings for allocation concealment and use the fixed‐effect model for our primary outcome. We identified a limited number of trials and we did not exclude any of them based on the ratings of allocation concealment. We were not able to carry out a sensitivity analysis due to the small number of trials. |
| ADHD: attention deficit hyperactivity disorder | |
| Name of rating scale | Description | Construction | Study | Source of Information used in the study |
| Aberrant Behaviour Checklist (ABC) (Aman 1985a; Aman 1985b) | Symptom checklist for assessing problem behaviours of children and adults with mental retardation. It is also used for classifying problem behaviours of children and adolescents with mental retardation. | 58 items, 5 scales.
| Parent/caregiver | |
| Child Behaviour Checklist (CBCL) (Achenbach 1991)
| Checklist for evaluating maladaptive behavioural and emotional problems. | 113 items, 8 subscales.
| Parent | |
| Overt Aggression Scale (OAS) (Yudofsky 1986) | Assesses the severity and frequency of overt aggression. | 25 items, 4 subscales.
Within each category, aggressive behaviour is rated according to its severity. | Parent | |
| Overt Aggression Scale ‒ Modified (OAS‐M) (Kay 1988) | Assesses the severity and frequency of overt aggression. | 20 items, 4 subscales.
5‐point interval scale that represents increasing level of aggression. The total aggression score is obtained by multiplying the 4 individual scales by weights of 1, 2, 3 or 4 and then summing the 4 weighted scores. | Nurse or teacher | |
| Rating of aggression against people and/or property scale (RAAP) (Kemph 1993) | ‐ | Global rating scale, 1 item. Scored from 1 (no aggression reported) to 5 (intolerable behaviour). | Clinician | |
| Children's Aggression Scale ‒ Parent (CAS‐P; Halperin 2002) and Teacher (CAS‐T; Halperin 2003) | Retrospectively measures the frequency and severity of 4 categories of aggression: verbal aggression; aggression against objects and animals; provoked physical aggression; and initiated physical aggression | Respondents (parents/guardians and teachers) complete a Likert scale to evaluate the frequency of an act. The frequency of aggressive events is multiplied by its designated severity weight factor and then summed to yield a total score. | Parent and teacher | |
| Antisocial Behavior Scale (ABS) Proactive and Reactive Subscales (Brown 1996) | Instrument used to differentiate reactive/affective from proactive subtypes of aggression | 28 items. Proactive Aggression subscale: 5 proactive items and 5 covert antisocial items. Reactive Aggression subscale: 6 items. | Parent |
| Name of rating scale | Description | Construction | Study | Source of information used in the study |
| Conners' Parent Rating Scale (CPRS) (Conners 1989) | Checklist for assessing behavioural and emotional difficulties. | 48 items, 6 subscales.
| Parent | |
| Nisonger Child Behaviour Rating Form (NCBRF) (Aman 1996; Tassé 1996) | Assesses behaviour of children and adolescents with intellectual disability or autism spectrum disorders, or both. | 76 items, 8 subscales.
| Parent | |
| Nisonger Child Behavior Rating Form ‒ Typical IQ D‐Total (includes conduct problems and oppositional subscales) | Typical IQ version: assesses behaviour of children and adolescents with normal IQ. | 10 items, 1 prosocial subscale.
54 items, 6 problem behaviour subscales.
| Parent | |
| IQ: intelligence quotient. | ||||
| Study ID | General | Neurological | Gastrointestinal | Respiratory | Cardiovascular/Metabolic | Serious adverse event (unspecified) | Other |
| (risperidone = 12, placebo = 13) |
|
|
| ‐ | Not reported | ‐ | ‐ |
| (risperidone = 19, placebo = 19) |
|
|
|
| Not reported | ‐ | ‐ |
| (quetiapine = 9, placebo = 10) |
|
| ‐ | ‐ | No differences across groups found on ECG QRS or QTc intervals. | ‐ | ‐ |
| (risperidone = 10, placebo = 10) |
| ‐ |
| ‐ | No clinically significant changes in ECG. | ‐ |
|
| (risperidone = 6, placebo = 7) | No side effects reported in any category. | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| (risperidone = 55, placebo = 63) |
|
|
|
|
| ‐ | ‐ |
| (risperidone = 172, placebo = 163) |
|
|
|
|
|
| ‐ |
| (risperidone = 53, placebo = 57) |
|
|
|
|
|
|
|
| (risperidone = 73, placebo = 80) |
|
|
|
|
| ‐ |
|
| (ziprasidone = 25, placebo = 25) |
|
|
|
|
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| Bpm: beats per minute; ECG: electrocardiogram; URTI: upper respiratory tract infection; EPSE: Extrapyramidal side effects; QRS: the name for the 3 waves (Q wave, R wave and S wave) on an electrocardiogram; QTc: correct QT (start of Q wave to end of T wave) interval | |||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Aggression: ABC irritability (mean change scores) Show forest plot | 3 | 238 | Mean Difference (IV, Random, 95% CI) | ‐6.49 [‐8.79, ‐4.19] |
| 2 Aggression: OAS‐M, ABS Reactive subscale (final scores) Show forest plot | 2 | 190 | Mean Difference (IV, Random, 95% CI) | ‐1.30 [‐2.21, ‐0.40] |
| 3 Aggression: OAS‐M, ABS Proactive subscale (final scores) Show forest plot | 2 | 190 | Mean Difference (IV, Random, 95% CI) | ‐1.12 [‐2.30, 0.06] |
| 4 Conduct: NCBR‐CP (mean change scores) Show forest plot | 2 | 225 | Mean Difference (IV, Random, 95% CI) | ‐8.61 [‐11.49, ‐5.74] |
| 5 Weight gain (antipsychotic only): Kg (mean change scores) Show forest plot | 2 | 138 | Mean Difference (IV, Random, 95% CI) | 2.37 [0.26, 4.49] |
| 6 Weight gain (antipsychotic and stimulant): Kg (mean change scores) Show forest plot | 3 | 305 | Mean Difference (IV, Random, 95% CI) | 2.14 [1.04, 3.23] |
