Table 1.

Grading of Recommendations Assessment, Development and Evaluation evidence profiles

Outcome assessed; number of studies; number of patients; duration of studies	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Dose–response effect present?	Summary of findings	Overall quality
Psychostimulants for aggression, oppositional behaviour, and conduct problems in youth with ADHD, with and without ODD and CD
Aggression, oppositional behaviour, conduct problems;	Some limitations in study quality	No serious inconsistency	No indirectness	No serious imprecision	Publication bias unlikely	Evidence of dose–response effect for this outcome	Studies 1970 to 2001	High
							Effect size (Cohen d)
							Clinician 0.77, 95% CI 0.63 to 0.88
40 RCTs;							Parent 0.71, 95% CI 0.42 to 1.15
							Teacher 1.04, 95% CI 0.79 to 1.32
2364 patients;							Studies 2002 to 2013
2 to 16 weeks							SMD
							Parent 0.55, 95% CI 0.36 to 0.73
							Teacher 0.84, 95% CI 0.59 to 1.10
Clonidine (monotherapy or in combination with a psychostimulant) for oppositional behaviour, and conduct problems in youth with ADHD, with and without ODD and CD
Oppositional behaviour and conduct problems;	Major limitations in study quality	Inconsistency in results between studies	No indirectness	Some imprecision of results	Possible publication bias	No evidence of dose–response effect for this outcome	SMD, clonidine, compared with placebo: 0.27, 95% CI 0.04 to 0.51	Very lowa
6 RCTs;
545 patients;
6 to 16 weeks
Guanfacine (monotherapy or in combination with a psychostimulant) for oppositional behaviour in youth with ADHD, with and without ODD
Oppositional behaviour;	Minor limitations in study quality	No inconsistency	No indirectness	No serious imprecision	Possible publication bias	No evidence of dose–response effect for this outcome	SMD, guanfacine, compared with placebo: 0.43, 95% CI 0.18 to 0.68	Moderateb
2 RCTs;
678 patients;
8 to 9 weeks
Atomoxetine for oppositional behaviour in youth with ADHD, with and without ODD and CD
Oppositional behaviour;	No serious limitations in study quality	No major inconsistency	No indirectness	No serious imprecision	Publication bias unlikely	Dose–response effect not demonstrated for this outcome	Effect size, atomoxetine, compared with placebo: 0.33, 95% CI 0.24 to 0.43	High
15 RCTs;
1907 patients;
4 to 18 weeks

^aOverall quality was downgraded based on study quality and inconsistency in results between studies.

^bOverall quality was downgraded based on study quality.

ADHD = attention-deficit hyperactivity disorder; CD = conduct disorder; ODD = oppositional defiant disorder; RCT = randomized controlled trial; SMD = standardized mean difference