TABLE 2.
Trial Outcomes
| Group Means Across Assessments Least-Squares Means (SD)a |
Fixed Effects F (df=105) P |
Between-Group Contrastsb Differences in Least-Squares Means [95% CI] Effect Sizec Significance test |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stimulant respondersd | Risperidone adjunctive to stimulant | Divalproex sodium adjunctive to stimulant | Placebo adjunctive to stimulant | Tx | Time | Tx by Time | RISP-PBO | DVPX-PBO | DVPX-RISP | ||||||||
| Baseline | Stim optim end | Baseline | Stim optim end | RCT end | Baseline | Stim optim end | RCT end | Baseline | Stim optim end | RCT end | |||||||
| R-MOAS, square-root | 7.42 (1.93) |
1.91 (1.94) |
7.91 (1.62) |
6.57 (1.61) |
3.33 (1.90) |
8.16 (1.58) |
6.12 (1.63) |
3.95 (1.91) |
7.56 (1.90) |
6.43 (1.90) |
5.41 (1.95) |
0.49 .62 |
58.34 <.001 |
2.77 .03 |
−2.33 [−3.83, −0.82] |
−1.60 [−3.18, −0.03] |
0.72 [−0.59, 2.04] |
| −1.32 | −0.91 | 0.45 | |||||||||||||||
|
t = −3.07, p = .003 |
t = −2.02, p = .046 |
t = 1.09, p = .277 |
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| CBCL Aggressive Behavior, T | 75.81 (8.96) |
61.16 (9.11) |
77.25 (6.89) |
72.62 (6.85) |
61.75 (8.19) |
78.67 (6.59) |
72.21 (6.86) |
63.88 (9.09) |
77.83 (7.64) |
73.03 (7.64) |
71.36 (8.17) |
1.30 .28 |
42.38 <.001 |
2.72 .03 |
−9.11 [−14.86, −36] |
−7.48 [−13.93, −1.03] |
1.63 [−3.90, 7.16] |
| −1.25 | −1.03 | 0.24 | |||||||||||||||
|
t = −3.15, p = .002 |
t = −2.30, p = .023 |
t = 0.58, p = .560 |
|||||||||||||||
| CBCL Rulebreaking Behavior, T | 72.42 (7.34) |
63.64 (7.47) |
71.83 (7.34) |
69.02 (7.47) |
60.07 (4.11) |
72.51 (4.09) |
68.68 (4.92) |
63.96 (3.94) |
71.85 (4.11) |
69.85 (5.48) |
68.07 (4.63) |
2.74 (4.63) |
48.83 (4.95) |
5.04 .07 |
−7.58 [−11.08, −4.09] |
−3.87 [−7.79, 0.06] |
3.72 [0.35, 7.08] |
| <.001 | <.001 | −1.73 | |||||||||||||||
|
t = −4.31, p = .000 |
t = −1.96, p = .053 |
t = 2.19, p = .031 |
|||||||||||||||
| CBCL Internalizing Behavior, T | 60.45 (9.06) |
51.05 (9.21) |
61.82 (7.07) |
57.53 (7.04) |
49.60 (8.36) |
61.90 (6.75) |
59.18 (7.01) |
51.21 (9.20) |
61.68 (7.78) |
59.38 (7.78) |
57.57 (8.30) |
1.07 0.35 |
22.91 <.001) |
1.78 0.14 |
−7.11 [−12.83, −1.39] |
−6.37 [−12.80, 0.05] |
0.74 [−4.77, 6.25] |
| −0.95 | −0.85 | 0.106 | |||||||||||||||
|
t = −2.47, p = .015 |
t = −1.97, p = .052 |
t = 0.27, p = .791 |
|||||||||||||||
| Conn-GI, Restless & Inattentive, T | 85.25 (14.09) |
58.43 (14.15) |
82.01 (8.32) |
68.84 (8.26) |
60.25 (9.70) |
83.66 (8.06) |
65.54 (8.32) |
64.27 (9.71) |
84.21 (9.67) |
70.61 (9.67) |
68.97 (9.89) |
1.17 .31 |
75.33 <.001 |
1.63 .17 |
−6.73 [−14.19, 0.73] |
−1.89 [−9.71, 5.93] |
4.84 [−1.68, 1.37] |
| −0.75 | −0.21 | 0.59 | |||||||||||||||
|
t = −1.79, p = .077 |
t = −0.48, p = .633 |
t = 1.47, p = .144 |
|||||||||||||||
| Conn-GI, Emotional Lability, T | 81.9 (11.92) |
55.37 (12.00) |
80.86 (9.21) |
71.87 (9.10) |
55.23 (11.01) |
81.80 (9.05) |
70.55 (9.46) |
64.28 (11.26) |
79.36 (10.94) |
75.76 (10.94) |
68.34 (11.35) |
1.87 .16 |
33.05 <.001 |
2.34 .06 |
−11.91 [−21.80, −2.01] |
−2.68 [−13.02, 7.67] |
9.23 [0.69,17.78] |
| −1.18 | −0.26 | 1.01 | |||||||||||||||
|
t = −2.39, p = .019 |
t = −0.51, p = .609 |
t = 2.14, p = .034 |
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| Child Depression Rating Scale | 34.53 (21.47) |
25.98 (21.49) |
36.62 (14.16) |
32.14 (14.14) |
26.18 (14.75) |
37.61 (13.06) |
33.74 (13.16) |
29.58 (14.29) |
37.52 (12.08) |
33.86 (11.82) |
35.12 (12.16) |
1.89 0.16 |
12.82 <.001 |
1.63 0.17 |
−7.62 [−13.58, −1.67] |
−5.51 [−12.06, 1.03] |
2.11 [−3.34, 7.56] |
| −0.58 | −0.42 | 0.15 | |||||||||||||||
|
t = −2.48, p = .015 |
t = −1.46, p = .148 |
t = 0.90, p = .369 |
|||||||||||||||
| Columbia Impairment Scale | 29.29 (10.23) |
16.24 (10.48) |
31.08 (8.06) |
24.48 (8.02) |
20.16 (9.85) |
30.93 (7.87) |
26.05 (7.94) |
23.62 (11.17) |
29.96 (9.52) |
28.09 (9.42) |
25.37 (9.80) |
0.64 0.53 |
11.50 <.001 |
0.79 0.54 |
−3.97 [−10.96, 3.03] |
−1.22 [−9.14, 6.70] |
2.75 [−4.09, 9.58] |
| (−0.4) | (−0.13) | (0.336) | |||||||||||||||
|
t = −1.13, p = .263 |
t = −0.31, p = .760 |
t = 0.80, p = .427 |
|||||||||||||||
| Body Mass Index, z-score | 0.47 (1.23) |
0.18 (1.23) |
0.05 (0.96) |
−0.18 (0.96) |
0.43 (1.00) |
0.14 (0.88) |
−0.17 (0.89) |
−0.17 (0.93) |
0.18 (0.84) |
−0.18 (0.82) |
−0.24 (0.84) |
1.57 0.21 |
8.30 <.001 |
6.44 <.001 |
0.74 [0.39, 1.09] |
0.09 [−0.28, 0.46] |
−0.65 [−0.96, −0.34] |
| 0.815 | 0.097 | −0.70 | |||||||||||||||
|
t = 4.16, p = .000 |
t = 0.47, p = .637 |
t = −4.18, p = .000 |
|||||||||||||||
| Weight, kg | 34.32 (11.91) |
34.08 (11.91) |
34.68 (8.73) |
35.07 (8.71) |
37.30 (8.83) |
35.13 (7.94) |
35.31 (7.96) |
35.96 (8.10) |
36.05 (6.91) |
34.48 (6.81) |
34.50 (6.90) |
0.24 0.79 |
2.47 0.09 |
3.28 0.01 |
3.18 [1.19, 5.17] |
1.50 [−0.61, 3.62] |
−1.68 [−3.38, 0.02] |
| 0.404 | 0.190 | −0.20 | |||||||||||||||
|
t = 3.17, p = .002 |
t = 1.41, p = .161 |
t = −1.96, p = .053 |
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NOTE: CBCL = Child Behavior Checklist; CI = confidence interval; ConnGI = Conners Global Index – Parent Version; DVPX = divalproex sodium; PBO = placebo; R-MOAS = Retrospective – Modified Overt Aggression Scale; RCT = randomized controlled trial; RISP = risperidone; Stim optim end = stimulant optimization phase endpoint; Tx = treatment.
a
Least-squares means and SDs across assessment times are adjusted for random effect of site.
b
Contrasts are the differences in least-squares means in RCT endpoints between groups, adjusted for site, baseline and stimulant optimization endpoint assessments.
c
Effect sizes are Hedge’s g, which adjusts Cohen’s d for small sample sizes and is interpretively identical to it.
d
Data for those whose aggressive behavior remitted during stimulant optimization are Presented for reference; they were not included in the mixed effects analyses shown.