Table 2.

Summary of efficacy for ADHD Rating Scale IV outcomes

Study design Citation	Treatment comparison	Patients randomized (n)	Patients analyzed (n)	Main findings for ADHD-RS-IV	Risk of bias [27]	Effect size vs. PBO for ADHD-RS-IV total score
Autism spectrum disorder
RCT  Harfterkamp, 2012 [38]	ATX 1.2 mg/kg vs. PBO	97	ATX: 48 PBO: 49	Significantly greater improvements in total score, inattention, and hyperactivity/impulsivity subscale scores with ATX Mean difference from PBO: total score (– 6.7, P < 0.001), inattention subscore (– 2.7, P = 0.003), hyperactivity/impulsivity subscore (– 3.9, P < 0.001)	Low	0.87a (INV)
RCT  NCT00498173 [41]	ATX vs. PBO	60	ATX: 29 PBO: 31	Numerically greater improvements in total score, inattention, and hyperactivity/impulsivity subscale scores with ATX; statistical analyses NR	NR	NR
RCT  Scahill, 2015 [45]	GXR < 3 mg/day vs. PBO	62	GXR: 30 PBO: 32	Significantly greater improvements from baseline in total score and hyperactivity/impulsivity subscale scores with GXR (P < 0.0001)	Low	2.03 (INV)
Oppositional defiant disorder
MA  Cheng, 2007 [17]	ATX vs. PBO (MA; dose NA)	213	ATX: 137 PBO: 76	Significantly greater improvements in total score (SMD − 0.70, P < 0.05), inattention (SMD – 0.69, P < 0.05), and hyperactivity/impulsivity (SMD – 0.60, P < 0.05) subscale scores with ATX	NR	NR
MA  Schwartz, 2014 [20]	ATX vs. PBO (MA; dose NA)	3928	ODD ≤ 20% ATX: 521 PBO: 470 ODD > 20 to < 80% ATX: 1062 PBO: 677 ODD ≥ 80% ATX: 575 PBO: 392	Total score for ATX was superior to PBO (SMD: − 0.64, P < 0.0001) Total scores for ATX were similar irrespective of the presence of comorbid ODD (SMD ≤ 20% – 0.48 vs. SMD > 20 to < 80% – 0.63 vs. SMD ≥ 80% – 0.64, P = 0.17)	NR	NR
RCT  Connor, 2010 [31]	GXR (< 4 mg/day) vs. PBO	217	GXR: 138 PBO: 79	Significantly greater improvements in total score with GXR (least squares mean difference from baseline = 23.8 vs. 11.5, P < 0.001)	Low	0.92 (INV)
RCT  Kaplan, 2004 [39]	ATX (< 2 mg/kg) vs. PBO	98	ATX: 53 PBO: 45	Significant improvements in total score, inattention, and hyperactivity/impulsivity subscale scores compared with baseline with ATX but not PBO Significantly greater total score response rates (≥ 25% reduction) with ATX (65.4%) vs. PBO (36.4%), P = 0.007	Low	0.72 (parent:INV)
RCT  Newcorn, 2005 [42]	ATX (0.5, 1.2, 1.8 mg/kg) vs. PBO	115	ATX0.5: 21 ATX1.2: 27 ATX1.8: 34 PBO: 31	Significantly greater improvements in total score (mean change from baseline – 13.4, P = 0.03) and inattention subscale scores (mean change from baseline – 6.9, P = 0.02) with ATX 1.8 mg/kg	High	ATX0.5: 0.47a ATX1.2: 0.49 ATX1.8: 0.69 (parent:INV)
Tourette’s disorder and other tic disorders
RCT  Allen, 2005  [28]	ATX (< 1.5 mg/kg) vs. PBO	148	ATX: 76 PBO: 72	Significantly greater improvements in total score, inattention, and hyperactivity/impulsivity subscale scores with ATX compared with PBO	Moderate	0.6 (parent:INV)
RCT  Scahill, 2001  [44]	GXR (< 4 mg/day) vs. PBO	34	GXR: 17 PBO: 17	Significantly greater improvements in (teacher-rated) total score, inattention, and hyperactivity/impulsivity subscale scores with GXR	Moderate	1.23 (teacher:INV)
Generalized anxiety disorder and major depressive disorder
RCT  Bangs, 2007  [29]	ATX (< 1.8 mg/day) vs. PBO	142	ATX: 72 PBO: 70	Significantly greater improvements in total score from baseline with ATX compared with PBO	Low	0.84 (parent:INV)
RCT  Geller, 2007  [34]	ATX (< 1.2 mg/kg) vs. PBO	176	ATX: 55 PBO: 58	Significantly greater improvements in total score (mean difference compared with PBO: − 10.5, P < 0.001), inattention, and hyperactivity/impulsivity subscale scores with ATX Significantly higher response rate (≥ 25% reduction in total score from baseline) with ATX (61.8% vs. 12.1%, P < 0.001)	Moderate	1 (INV)
RCT  Griffiths, 2018  [35]	ATX (< 1.4 mg/kg) vs. PBO	140	ATX: 38 PBO: 38	Significantly greater improvements in ADHD-RS-IV total score with ATX	Low	0.46 (parent:INV)

NA Not applicable, SMD standardized mean difference; for other abbreviations, see footnote of Table 1

^aCalculated from published data