Table 2.
Testing for Moderators of Treatment Effects and Predictors of Outcomea
| Sites: | n | Interaction Effects | PREDICTOR EFFECTSa | ||||||
|---|---|---|---|---|---|---|---|---|---|
| RR (95%CI) Risperidone vs. Lithium | p | RR (95%CI) Risperidone vs. Divalproex | P | RR (95%CI) Lithium vs. Divalproex | p | RR (95%CI) | p | ||
| PITT | 39 | 1.2 (0.8, 1.7) | 0.369 | 1.3 (0.8, 2.2) | 0.307 | 1.1 (0.6, 1.9) | 0.736 | ||
| CNMC | 68 | 1.4 (0.9, 2.1) | 0.085 | 1.5 (1.0, 2.3) | 0.049 | 1.1 (0.6, 1.8) | 0.762 | ||
| WASHU. | 63 | 2.6 (1.1, 6.0) | 0.022 | 9.6 (2.4, 38.2) | 0.001 | 3.7 (0.8, 17.1) | 0.096 | ||
| UTMB/UTSW | 59 | 8.3 (1.1, 60.8) | 0.037 | 10.5 (1.4, 77.7) | 0.021 | 1.3 (0.1, 19.0) | 0.866 | ||
| JHMI | 50 | 4.2 (1.1, 16.2) | 0.039 | 3.1 (1.0, 9.5) | 0.043 | 0.8 (0.1, 3.9) | 0.739 | ||
| Interaction: | χ2= 8.5 | 0.076 | χ2 = 11.8 | 0.019 | χ2 = 2.5 | 0.638 | |||
| Age | |||||||||
| 6 to 12 yr | 218 | 1.8 (1.3, 2.7) | 0.001 | 2.8 (1.8, 4.3) | <0.0001 | 1.5 (0.9, 2.5) | 0.093 | 1.0 | |
| 13 yr or greater | 61 | 2.0 (1.0, 3.9) | 0.041 | 2.4 (1.1, 5.7) | 0.038 | 1.2 (0.4, 3.4) | 0.708 | 1.1 (0.9, 1.4) | 0.316 |
| Age (continuous) | Interaction | χ2 = 1.0 | 0.328 | χ2= 0.04 | 0.847 | χ2 = 0.2 | 0.687 | 1.0 (0.99, 1.07) | 0.139 |
| Age-onset | |||||||||
| Less than 8 yr | 237 | 2.2 (1.5, 3.12) | <0.0001 | 2.8 (1.9, 4.2) | <0.0001 | 1.3 (0.8, 2.1) | 0.283 | 1.0 | |
| 8 yr or above | 42 | 1.2 (0.7, 2.2) | 0.521 | 3.2 (0.9, 11.8) | 0.075 | 2.7 (0.7, 10.1) | 0.148 | 1.1 (0.8, 1.4) | 0.693 |
| Age-onset (continuous) | Interaction | χ2 = 3.2 | 0.076 | χ2 = 0.2 | 0.651 | χ2= 1.8 | 0.181 | 1.0 (1.0, 1.1) | 0.222 |
| Severity of ADHD | Interaction | χ2 =4.1 | 0.044 | χ2 =0.9 | 0.344 | χ2 =0.1 | 0.794 | 0.97 (0.95,1.00) | |
| ADHD: | |||||||||
| no | 20 | 1.0 (0.6,1.8) | 1.000 | 1.0 | |||||
| yes | 259 | 2.1 (1.5, 3.0) | <0.0001 | b | b | 0.8 (0.6, 1.2) | |||
| Interaction | χ2 = 5.0 | 0.025 | |||||||
| Severity of ODD | Interaction | χ2= 2.3 | 0.131 | χ2= 1.2 | 0.278 | χ2= 3.4 | 0.064 | 1.01 (0.95, 1.07) | 0.822 |
| ODD: | |||||||||
| no | 28 | 1.3 (0.6, 2.7) | 0.579 | 4.1 (1.1, 15.1) | 0.032 | 3.3 (0.8, 14.0) | 0.106 | 1.9 | |
| yes | 251 | 2.0 (1.4, 2.8) | <0.0001 | 2.7 (1.8, 4.1) | <0.0001 | 1.4 (0.9, 2.2) | 0.178 | 1.1 (0.8, 1.5) | 0.594 |
| χ2=1.1 | 0.293 | χ2=0.4 | 0.552 | χ2=1.3 | 0.261 | ||||
| Sex: | |||||||||
| males | 139 | 2.3 (1.5, 3.5) | <0.0001 | 3.0 (1.7, 5.1) | <0.0001 | 1.3 (0.7, 2.4) | 0.449 | −1.0 | |
| females | 140 | 1.6 (1.0, 2.5) | 0.046 | 2.7 (1.6, 4.6) | <0.0001 | 1.7 (0.9, 3.2) | 0.076 | 1.1 (0.9, 1.4) | 0.349 |
| Interaction: | χ2= 1.4 | 0.231 | χ2= 0.03 | 0.853 | χ2 = 0.5 | 0.499 | |||
| Race: | |||||||||
| White | 203 | 1.8 (1.2, 2.7) | 0.002 | 3.0 (1.9, 4.9) | <0.0001 | 1.7 (1.0, 2.9) | 0.064 | 1.1 (0.8, 1.4) | 0.629 |
| Other | 76 | 2.1 (1.2, 3.7) | 0.008 | 2.3 (1.3, 4.1) | 0.006 | 1.1 (0.5, 2.3) | 0.847 | −1.0 | |
| Interaction: | χ2 = 0.2 | 0.657 | chi-2 = 0.6 | 0.454 | chi-2 = 0.9 | 0.357 | |||
| Social Status: | |||||||||
| 4 or 5 | 174 | 2.0 (1.3, 2.9) | <0.0001 | 2.8 (1.8, 4.4) | <0.0001 | 1.4 (0.8, 2.4) | 0.188 | 1.0 | |
| 3 and below | 105 | 1.9 (1.1, 3.3) | 0.021 | 3.1 (1.5, 6.2) | 0.002 | 1.6 (0.7, 3.7) | 0.249 | 0.9 (0.7, 1.1) | 0.28 |
| Interaction: | χ2 = 0.01 | 0.909 | χ2= 0.04 | 0.841 | χ2= 0.1 | 0.804 | |||
| Puberty status: | |||||||||
| Pubertal | 102 | 1.8 (1.1, 2.8) | 0.016 | 3.2 (1.6, 6.3) | 0.001 | 1.8 (0.8, 3.9) | 0.138 | −1.0 | |
| Pre-pubertal | 177 | 2.0 (1.3, 3.1) | 0.001 | 2.7 (1.7, 4.2) | <0.0001 | 1.3 (0.8, 2.3) | 0.314 | 0.9 (0.7, 1.1) | 0.197 |
| Interaction: | χ2= 0.2 | 0.681 | χ2= 0.2 | 0.683 | χ2= 0.4 | 0.534 | |||
| Family history of bipolar disorder | |||||||||
| no | 154 | 1.7 (1.2, 2.4) | 0.006 | 3.1 (1.9, 5.1) | <0.0001 | 1.9 (1.0, 3.3) | 0.036 | 1.0 | |
| yes | 104 | 1.9 (1.1, 3.3) | 0.033 | 2.3 (1.3, 4.3) | 0.006 | 1.3 (0.6, 2.6) | 0.529 | 1.0 (0.9, 1.2) | 0.608 |
| Interaction: | χ2 = 0.1 | 0.745 | χ2= 0.4 | 0.544 | χ2= 0.6 | 0.444 | |||
| Severity of Mania | |||||||||
| 5 | 52 | 1.2 (0.6, 2.2) | 0.644 | 2.4 (1.1, 5.3) | 0.030 | 2.1 (0.9, 4.8) | 0.096 | −1.0 | |
| 6 | 175 | 2.4 (1.6, 3.7) | <0.0001 | 3.0 (1.9, 4.7) | <0.0001 | 1.2 (0.7, 2.2) | 0.502 | 0.9 (0.6, 1.1) | 0.251 |
| 7 | 52 | 1.3 (0.6, 2.8) | 0.563 | 2.8 (0.9, 9.0) | 0.084 | 2.2 (0.7, 7.3) | 0.192 | 0.8 (0.5, 1.2) | 0.297 |
| Interaction: | χ2= 4.7 | 0.095 | χ2= 0.2 | 0.895 | χ2 = 1.4 | 0.493 | |||
| Psychosis: | |||||||||
| no | 64 | 1.6 (0.9, 2.7) | 0.109 | 3.3 (1.3, 8.5) | 0.012 | 2.1 (0.8, 5.7) | 0.137 | −1.0 | |
| yes | 215 | 2.1 (1.4, 3.1) | <0.0001 | 2.8 (1.8, 4.2) | <0.0001 | 1.3 (0.8, 2.2) | 0.303 | 1.1 (0.8, 1.4) | 0.546 |
| Interaction: | χ2= 0.7 | 0.403 | χ2= 0.1 | 0.718 | χ2 = 0.7 | 0.401 | |||
| Number of comorbidities: | |||||||||
| ≤ 1 | 59 | 1.5 (0.9, 2.7) | 0.148 | 2.2 (1.1, 4.1) | 0.017 | 1.4 (0.7, 3.0) | 0.373 | −1.0 | |
| >1 | 220 | 2.1 (1.4, 3.0) | <0.0001 | 3.2 (2.0, 5.1) | <0.0001 | 1.6 (0.9, 2.7) | 0.110 | 0.9 (0.7, 1.1) | 0.266 |
| Interaction: | χ2 = 0.7 | 0.404 | χ2 = 1.0 | 0.327 | χ2 = 0.04 | 0.833 | |||
| Conduct Disorder (CD): | |||||||||
| no | 235 | 2.0 (1.4, 2.7) | <0.0001 | 2.8 (1.9, 4.1) | <0.0001 | 1.4 (0.9, 2.3) | 0.127 | −1.0 | |
| yes | 44 | 1.8 (0.7, 4.7) | 0.256 | 5.6 (0.8, 39.6) | 0.081 | 3.2 (0.4, 25.1) | 0.268 | 0.7 (0.4, 1.1) | 0.096 |
| Interaction: | χ2 = 0.04 | 0.833 | χ2 = 0.5 | 0.492 | χ2 = 0.6 | 0.454 | |||
| On stimulant medication: | |||||||||
| no | 189 | 1.8 (1.2, 2.6) | 0.002 | 2.6 (1.7, 4.0) | <0.0001 | 1.5 (0.9, 2.5) | 0.137 | −1.0 | |
| yes | 90 | 2.3 (1.2, 4.2) | 0.008 | 3.6 (1.6, 7.7) | 0.001 | 1.5 (0.6, 3.8) | 0.346 | 0.9 (0.7, 1.2) | 0.520 |
| Interaction: | χ2 = 0.5 | 0.482 | χ2= 0.5 | 0.498 | χ2 = 0.01 | 0.925 | |||
| History of Major Depression | |||||||||
| no | 74 | 2.2 (1.2, 3.9) | 0.007 | 4.0 (1.6, 10.1) | 0.003 | 1.8 (0.7, 5.1) | 0.245 | −1.0 | |
| yes | 205 | 1.8 (1.3, 2.7) | 0.001 | 2.6 (1.7, 4.0) | <0.0001 | 1.4 (0.9, 2.4) | 0.165 | 1.0 (0.8, 1.3) | 0.894 |
| Interaction: | χ2= 0.3 | 0.614 | χ2= 0.7 | 0.413 | χ2= 0.2 | 0.669 | |||
| Suicidality: | |||||||||
| not suicidal | 123 | 1.8 (1.2, 2.7) | 0.005 | 2.8 (1.6, 4.9) | <0.0001 | 1.6 (0.9, 2.9) | 0.147 | −1.0 | |
| suicidal | 156 | 2.2 (1.3, 3.6) | 0.002 | 2.9 (1.7, 4.8) | <0.0001 | 1.3 (0.7, 2.7) | 0.403 | 0.9 (0.7, 1.2) | 0.501 |
| Interaction: | χ2= 0.4 | 0.550 | χ2= 0.00 | 0.961 | χ2= 0.2 | 0.703 | |||
| Obesity (BMI>95th perc.): | |||||||||
| no | 233 | 2.3 (1.6, 3.3) | <0.0001 | 2.9 (1.9, 4.3) | <0.0001 | 1.3 (0.7, 2.1) | 0.398 | −1.0 | |
| yes | 46 | 1.1 (0.6, 2.0) | 0.664 | 2.8 (1.1, 7.3) | 0.031 | 2.5 (1.00, 6.4) | 0.058 | 1.2 (0.9, 1.6) | 0.169 |
| Interaction: | χ2 = 4.1 | 0.044 | χ2 = 0.00 | 0.988 | χ2 = 1.6 | 0.208 | |||
| High maternal warmth: | |||||||||
| no | 177 | 2.1 (1.3, 3.3) | 0.002 | 3.1 (1.8, 5.4) | <0.0001 | 1.5 (0.8, 2.9) | 0.233 | −1.0 | |
| yes | 101 | 1.6 (1.1, 2.4) | 0.014 | 2.5 (1.5, 4.1) | <0.0001 | 1.6(0.9, 2.8) | 0.139 | 1.2 (0.9, 1.5) | 0.297 |
| Interaction: | χ2= 0.7 | 0.415 | χ2 = 0.3 | 0.584 | χ2 = 0.01 | 0.923 | |||
Note: Binary outcome: responder vs. non-responder status at end of treatment based on the on the Clinical Global Impressions for Bipolar Illness-Improvement Mania scale (CGI-BP-IM) at week 8. Consistent with the primary analysis of the clinical trial, patients who dropped out were considered non-responders. The response ratio (RR) is the ratio between the response rate in one treatment group vs. another, in pair-wise comparison. ADHD = attention-deficit/hyperactivity disorder; BMI = body mass index; CI = confidence interval; CNMC = Children’s National Medical Center; JHMI = Johns Hopkins Medical Institutions; ODD = oppositional defiant disorder; PITT = University of Pittsburgh; UTMB/UTSW = University of Texas at Galveston and at Dallas; WASHU = Washington University.
a
The models include site by medication interaction and the variable in the corresponding row
b
RR cannot be computed for these comparisons as response probability in patients with ADHD receiving divalproex is 0.