Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory.

OBJECTIVE: Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory. METHODS: A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6-12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone). RESULTS: At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83). CONCLUSIONS: Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302.

Severely Aggressive Children Receiving Stimulant Medication Versus Stimulant and Risperidone: 12-Month Follow-Up of the TOSCA Trial.

OBJECTIVE: The objective of this study was to evaluate 52-week clinical outcomes of children with co-occurring attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorder, and serious physical aggression who participated in a prospective, longitudinal study that began with a controlled, 9-week clinical trial comparing the relative efficacy of parent training + stimulant medication + placebo (Basic; n = 84) versus parent training + stimulant + risperidone (Augmented; n = 84). METHOD: Almost two-thirds (n = 108; 64%) of families in the 9-week study participated in week 52 follow-ups (Basic, n = 55; Augmented, n = 53) and were representative of the initial study sample. The assessment battery included caregiver and clinician ratings and laboratory tests. RESULTS: Only 43% of participants in the Augmented group and 36% in the Basic group still adhered to their assigned regimen (not significant [NS]); 23% of those in the Augmented group and 11% in the Basic group were taking no medication (NS). Both randomized groups improved baseline to follow-up, but the 3 primary parent-reported behavioral outcomes showed no significant between-group differences. Exploratory analyses indicated that participants in the Augmented group (65%) were more likely (p = .02) to have a Clinical Global Impressions (CGI) severity score of 1 to 3 (i.e., normal to mildly ill) at follow-up than those in the Basic group (42%). Parents rated 45% of children as impaired often or very often from ADHD, noncompliant, or aggressive behavior. The Augmented group had elevated prolactin levels, and the Basic group had decreased weight over time. Findings were generally similar whether groups were defined by randomized assignment or follow-up treatment status. CONCLUSION: Both treatment strategies were associated with clinical improvement at follow-up, and primary behavioral outcomes did not differ significantly. Many children evidenced lingering mental health concerns, suggesting the need for additional research into more effective interventions. Clinical trial registration information-Treatment of Severe Childhood Aggression (the TOSCA Study); http://clinicaltrials.gov/; NCT00796302.

Participant satisfaction in a study of stimulant, parent training, and risperidone in children with severe physical aggression.

OBJECTIVE: The purpose of this study was to examine the satisfaction of families who participated in the Treatment of Severe Childhood Aggression (TOSCA) study. METHODS: TOSCA was a randomized clinical trial of psychostimulant plus parent training plus placebo (basic treatment) versus psychostimulant plus parent training plus risperidone (augmented treatment) for children with severe physical aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder. Parents completed a standardized Parent Satisfaction Questionnaire (PSQ). RESULTS: Of the 168 families randomized, 150 (89.3%) provided consumer satisfaction data. When they were asked if they would join the study again if they had the option to repeat, 136 (91%) said "yes," 11 (7%) said "maybe," and one (<1%) said "no." When asked if they would recommend the study to other parents with children having similar problems, 147 (98%) said "yes" and 3 (2%) said "maybe." Between 71% (rating one aspect of the Parent Training) and 96% (regarding the diagnostic interview) endorsed study procedures using the most positive response option. Asked if there were certain aspects of the study that they especially liked, 64 (43%) spontaneously reported parent training. Treatment assignment (basic vs. augmented) and responder status were not associated with reported satisfaction. However, responder status was strongly associated with parent confidence in managing present (p<0.001) and future (p<0.005) problem behaviors. CONCLUSIONS: These findings indicate high levels of satisfaction with TOSCA study involvement and, taken together with previous pediatric psychopharmacology social validity studies, suggest high levels of support for the research experience. These findings may inform research bioethics and may have implications for deliberations of institutional review boards. TRIAL REGISTRY: Treatment of Severe Childhood Aggression (The TOSCA Study), NCT00796302, clinicaltrials.gov .

Risperidone added to parent training and stimulant medication: effects on attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression.

OBJECTIVE: In this study, we aimed to expand on our prior research into the relative efficacy of combining parent training, stimulant medication, and placebo (Basic therapy) versus parent training, stimulant, and risperidone (Augmented therapy) by examining treatment effects for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms and peer aggression, symptom-induced impairment, and informant discrepancy. METHOD: Children (6-12 years of age; N = 168) with severe physical aggression, ADHD, and co-occurring ODD/CD received an open trial of parent training and stimulant medication for 3 weeks. Participants failing to show optimal clinical response were randomly assigned to Basic or Augmented therapy for an additional 6 weeks. RESULTS: Compared with Basic therapy, children receiving Augmented therapy experienced greater reduction in parent-rated ODD severity (p = .002, Cohen's d = 0.27) and peer aggression (p = .02, Cohen's d = 0.32) but not ADHD or CD symptoms. Fewer children receiving Augmented (16%) than Basic (40%) therapy were rated by their parents as impaired by ODD symptoms at week 9/endpoint (p = .008). Teacher ratings indicated greater reduction in ADHD severity (p = .02, Cohen's d = 0.61) with Augmented therapy, but not for ODD or CD symptoms or peer aggression. Although both interventions were associated with marked symptom reduction, a relatively large percentage of children were rated as impaired for at least 1 targeted disorder at week 9/endpoint by parents (Basic 47%; Augmented 27%) and teachers (Basic 48%; Augmented 38%). CONCLUSION: Augmented therapy was superior to Basic therapy in reducing severity of ADHD and ODD symptoms, peer aggression, and symptom-induced impairment, but clinical improvement was generally context specific, and effect sizes ranged from small to moderate. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrials.gov/; NCT00796302.

What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder?

OBJECTIVE: Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested. METHOD: One hundred sixty-eight children 6 to 12 years old (mean age 8.89 ± 2.01 years) with severe physical aggression were randomized to a 9-week trial of PT, stimulant (STIM), and placebo (Basic treatment; n = 84) or PT, STIM, and risperidone (Augmented treatment; n = 84). All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder (n = 124) or conduct disorder (n = 44). Children received psychostimulant (usually Osmotic Release Oral System methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of week 3, placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (Disruptive-Total subscale was the primary outcome) and Antisocial Behavior Scale; blinded clinicians rated change on the Clinical Global Impressions scale. RESULTS: Compared with Basic treatment (PT + STIM [44.8 ± 14.6 mg/day] + placebo [1.88 mg/day ± 0.72]), Augmented treatment (PT + STIM [46.1 ± 16.8 mg/day] + risperidone [1.65 mg/day ± 0.75]) showed statistically significant improvement on the Nisonger Child Behavior Rating Form Disruptive-Total subscale (treatment-by-time interaction, p = .0016), the Nisonger Child Behavior Rating Form Social Competence subscale (p = .0049), and Antisocial Behavior Scale Reactive Aggression subscale (p = .01). Clinical Global Impressions scores were substantially improved for the 2 groups but did not discriminate between treatments (Clinical Global Impressions-Improvement score ≤2, 70% for Basic treatment versus 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment; other adverse events differed modestly from Basic treatment; weight gain in the Augmented treatment group was minor. CONCLUSIONS: Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behaviors when added to PT and optimized stimulant treatment. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study), URL: http://clinicaltrials.gov, unique identifier: NCT00796302.

A brief DSM-IV-referenced teacher rating scale for monitoring behavioral improvement in ADHD and co-occurring symptoms.

OBJECTIVE: To examine the psychometric properties of the 30-item teacher's version of the Child and Adolescent Symptom Inventory Progress Monitor (CASI-PM-T), a DSM-IV-referenced rating scale for monitoring change in ADHD and co-occurring symptoms in youths receiving behavioral or pharmacological interventions. METHOD: Three separate studies were conducted to determine (a) which items from longer diagnostic instruments were most representative of ADHD and commonly occurring psychiatric syndromes in clinic-referred samples ( N = 406) aged between 3 and 18 years, (b) the reliability and validity of the CASI-PM-T in students enrolled in full-time special education programs at the elementary and middle school levels (N = 169), and (c) the clinical utility of measuring behavioral change in a sample of outpatient ADHD children beginning treatment with stimulant medication. RESULTS: Internal consistency reliabilities (.71-.94), 2-week test-retest reliabilities (r = .70-.90), and interrater agreement (r = .44-.78) for the CASI-PM-T symptom categories were comparable to the full-length CASI-4. Convergence was also found between corresponding CASI-PM-T categories and consultant diagnoses of ADHD and ODD as well as school functioning measures of grade-point average and suspensions. The CASI-PM-T also demonstrated sensitivity to stimulant medication treatment effects. CONCLUSION: Findings provide preliminary support for the reliability, validity, and clinical utility of the CASI-PM-T.

Anxiety in boys with attention-deficit/hyperactivity disorder with and without chronic multiple tic disorder.

OBJECTIVE: This study examined the psychosocial and behavioral concomitants of anxiety in clinic-referred boys with attention-deficit/hyperactivity disorder (ADHD) with and without chronic multiple tic disorder (CMTD). METHOD: ADHD boys with (n = 65) and without (n = 94) CMTD were evaluated with measures of psychiatric symptoms, mental health risk factors, and academic and social performance. RESULTS: Boys with CMTD evidenced more severe anxiety and less social competence and were more likely to be living with only one biological parent than the ADHD Only group, but the magnitude of group differences was generally small. The severity of generalized anxiety, separation anxiety, social phobia, and obsessive-compulsive symptoms were uniquely associated with a different pattern of risk factors, and there was some evidence that these patterns differed for the two groups of boys. CONCLUSION: Boys with CMTD had a relatively more severe and complex pattern of anxiety that was associated with different clinical features, all of which suggests that ADHD plus CMTD might better be conceptualized as a distinct clinical entity from ADHD Only. However, findings from the extant literature are mixed, and therefore this remains a topic for further study.

Comparative study of children with ADHD only, autism spectrum disorder + ADHD, and chronic multiple tic disorder + ADHD.

OBJECTIVE: Identification of differences among children with ADHD only, autism spectrum disorder (ASD)+ADHD, and chronic multiple tic disorder (CMTD)+ADHD may lead to better understanding of clinical phenotypes. METHOD: Children were evaluated using the parent- and teacher-completed questionnaires. RESULTS: All three groups were highly similar in severity of oppositional defiant disorder and conduct disorder symptoms; however, the ASD+ADHD group generally exhibited the most severe anxiety, although the CMTD+ADHD group had the most severe generalized anxiety. The two comorbid groups had the most involved medical histories and the greatest likelihood of a family history of psychopathology. CONCLUSION: Groups differed in clinically meaningful ways, and the apparent association between tics and anxiety may explain in part the elevated levels of anxiety in both comorbid groups. Collectively, results suggest that ADHD may be better conceptualized as a family of interrelated syndromes defined in part by comorbid conditions and that continued research is clearly warranted.

Pregnancy-specific stress, prenatal health behaviors, and birth outcomes.

OBJECTIVE: Stress in pregnancy predicts earlier birth and lower birth weight. The authors investigated whether pregnancy-specific stress contributes uniquely to birth outcomes compared with general stress, and whether prenatal health behaviors explain this association. DESIGN: Three structured prenatal interviews (N = 279) assessing state anxiety, perceived stress, life events, pregnancy-specific stress, and health behaviors. MAIN OUTCOME MEASURES: Gestational age at delivery, birth weight, preterm delivery (<37 weeks), and low birth weight (<2,500 g). RESULTS: A latent pregnancy-specific stress factor predicted birth outcomes better than latent factors representing state anxiety, perceived stress, or life event stress, and than a latent factor constructed from all stress measures. Controlling for obstetric risk, pregnancy-specific stress was associated with smoking, caffeine consumption, and unhealthy eating, and inversely associated with healthy eating, vitamin use, exercise, and gestational age at delivery. Cigarette smoking predicted lower birth weight. Clinically-defined birth outcomes were predicted by cigarette smoking and pregnancy-specific stress. CONCLUSION: Pregnancy-specific stress contributed directly to preterm delivery and indirectly to low birth weight through its association with smoking. Pregnancy-specific stress may be a more powerful contributor to birth outcomes than general stress.

Methylphenidate in children with oppositional defiant disorder and both comorbid chronic multiple tic disorder and ADHD.

Our primary objective was to determine if immediate-release methylphenidate is an effective treatment for oppositional defiant disorder diagnosed from mother's report in children with both chronic multiple tic disorder and attention-deficit hyperactivity disorder (ADHD). Children (n = 31) aged 6 to 12 years received placebo and 3 doses of methylphenidate twice daily for 2 weeks each under double-blind conditions and were assessed with ratings scales and laboratory measures. Results indicated significant improvement in both oppositional and ADHD behaviors with medication; however, the magnitude of treatment effect varied considerably as a function of disorder (ADHD > Oppositional behaviors), informant (teacher > mother), assessment instrument, and specific oppositional behavior (rebellious > disobeys rules). Drug response was comparable with that in children (n = 26) who did not have diagnosed oppositional defiant disorder, but comorbidity appeared to alter the perceived benefits for ADHD according to mother's report. Methylphenidate is an effective short-term treatment for oppositional behavior in children with comorbid ADHD and chronic multiple tic disorder.

Predictors of psychiatric symptoms in children with an autism spectrum disorder.

This study examined mental health risk/protective factors for DSM-IV psychiatric symptoms in children with an autism spectrum disorder (ASD) and their contribution to functioning separate from ASD symptom severity. Mothers/teachers completed measures of risk/protection and social, adaptive, and school functioning in 6- to 12-year-olds with a diagnosed ASD (N = 238). Bivariate correlations and simultaneous regression analyses indicated a unique pattern of predictors for attention-deficit/hyperactivity disorder, aggression, anxiety, and depression symptoms. Moreover, psychiatric symptoms differentially predicted social and school performance. Findings indicate that co-occurring psychiatric symptoms and their associated mental health risk/protective factors may have important clinical implications and generally support a biopsychosocial model of psychopathology in children with an ASD that appears to share many similarities with models for non ASD children.

Immediate-release methylphenidate for ADHD in children with comorbid chronic multiple tic disorder.

OBJECTIVE: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). METHOD: Two cohorts of prepubertal children (N = 71) received placebo and three doses of MPH (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions as part of their involvement in a long-term observation study (1989-2004). Treatment effects were assessed with an extensive battery of parent-, teacher-, child-, and physician-completed rating scales and laboratory tasks. RESULTS: MPH-IR effectively suppressed ADHD, oppositional defiant disorder, and peer aggression behaviors. There was no evidence that MPH-IR altered the overall severity of tic disorder or obsessive-compulsive disorder behaviors. Teacher ratings indicated that MPH-IR therapy decreased tic frequency and severity. CONCLUSIONS: MPH-IR appears to be a safe and effective short-term treatment for ADHD in the majority of children with chronic tic disorder; nevertheless, the possibility of tic exacerbation in susceptible individuals warrants careful monitoring of all patients.

ODD, ADHD, versus ODD+ADHD in clinic and community adults.

OBJECTIVE: To seek evidence for the validity of oppositional defiant disorder (ODD) as a behavioral syndrome in adults. METHOD: Two samples of adults, mental health outpatient clinic referrals (N = 490) and community controls (N = 900), completed a Diagnostic and Statistic Manual of Mental Disorders-referenced rating scale and a brief questionnaire (social, educational, occupational, and treatment variables). Participants were separated into four groups: ODD-only, ADHD-only, ODD+ADHD, and NONE. RESULTS: In general, the three symptom groups were more severe than the NONE group; the ODD+ADHD and NONE groups were the most and least severe, respectively; and there were clear differences between the ODD-only and ADHD-only groups. The pattern of group differences was generally similar in both samples. CONCLUSION: Findings support the distinction between ADHD and ODD symptom presentations in adults, and the notion that the comorbid condition is a unique clinical entity, both of which are consistent with the child literature. Nevertheless, additional research with larger samples of patients will be necessary to establish ODD as a potential behavioral syndrome in adults.

Psychiatric comorbidity in ADHD symptom subtypes in clinic and community adults.

OBJECTIVE: To compare psychiatric comorbidity between the three symptom subtypes of Attention-Deficit/Hyperactivity Disorder (ADHD), Inattentive (I), Hyperactive-Impulsive (H), and Combined (C), in adults. METHOD: A clinic sample (N = 487) and a nonreferred community sample (N = 900) completed a DSM-IV-referenced rating scale and a questionnaire (social, educational, occupational, and treatment variables). Participants were assigned to one of four groups: ADHD:I, ADHD:H, ADHD:C, and NONE. RESULTS: All three ADHD symptom groups reported more severe comorbid symptoms than the NONE group; the ADHD:C and NONE groups were the most and least severe, respectively; and there were clear differences between the ADHD:I and ADHD:H groups. The pattern of group differences was similar in both samples. CONCLUSION: ADHD symptom subtypes in adults are associated with distinct clinical correlates. The diversity of self-reported psychopathology in adults who meet symptom criteria for ADHD highlights the importance of conducting broad-based evaluations.

A DSM-IV-referenced teacher rating scale for use in clinical management.

OBJECTIVE: Two studies were conducted to examine the psychometric properties of a DSM-IV-referenced teacher-completed rating scale in children receiving special education. METHOD: To assess reliability, teachers rated 74 students on two separate occasions (test-retest) using the teacher version of the Child Symptom Inventory-4 (CSI-4T), and teacher aides also rated the children on the first occasion (interrater). In a second study, teacher CSI-4T and Teacher's Report Form (TRF) ratings and consultant diagnoses were obtained for 101 students. RESULTS: Internal consistency reliabilities (0.72-0.94), 2-week test-retest reliabilities (r = 0.61-0.88), and interrater agreement (r = 0.19-0.56) for the CSI-4T major symptom categories were comparable with dimensional rating scales. CSI-4T ratings showed a consistent pattern of convergent and divergent validity with TRF scores and with consultant diagnoses. CONCLUSION: Findings provide preliminary support for the reliability and validity of the CSI-4T as a measure of DSM-IV symptoms in children receiving special education.

Further evidence of reliability and validity of the Child Symptom Inventory-4: parent checklist in clinically referred boys.

Examined reliability and validity of the parent version of the Child Symptom Inventory (CSI-4) in 247 boys between 6.0 and 10 years 11 months old referred for evaluation of behavioral and emotional problems. The CSI-4 is a behavior rating scale whose items correspond to the symptoms of disorders defined by the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994). Results indicated satisfactory internal consistency reliability, test-retest reliability, and temporal stability over a 4-year period for most symptom categories. CSI-4 ratings converged and diverged in a theoretically consistent pattern with respective scales of the Child Behavior Checklist (CBCL; Achenbach, 1991a) and the Diagnostic Interview for Children and Adolescents-Revised-Parent Version (DICA-P; Reich, Shayka, & Taibleson, 1991). Discriminant validity was established in that boys with specific DICA-P diagnoses received significantly higher corresponding CSI-4 parent symptom ratings than boys not so diagnosed. Clinical utility (sensitivity, specificity, positive predictive power, negative predictive power) was evaluated for screening cutoffs based on categorical (DSM-IV) and dimensional (normative distribution of Symptom Severity scores) scoring methods.

A DSM-IV-referenced, adolescent self-report rating scale.

OBJECTIVE: To examine the reliability and validity of the Youth's Inventory-4 (YI-4), a DSM-IV-referenced self-report rating scale. METHOD: Youths (N = 239) aged between 11 and 18 years who were clinically evaluated between 1996 and 1999 completed the YI-4, and 79% completed at least one additional self-report. Parents and teachers completed a companion measure. A second sample (N = 47) was retested 2 weeks after an initial evaluation. RESULTS: The YI-4 demonstrated satisfactory internal consistency (alpha values = .66-.87) and test-retest reliability (r values = 0.54-0.92), convergent and to lesser extent divergent validity with other self-report measures, and discriminant validity by differentiating children with and without diagnosed attention-deficit/hyperactivity disorder, conduct disorder, substance use, generalized anxiety disorder, or major depressive disorder. Youth-parent (r values = 0.05-0.50) and youth-teacher (r values < 0.18) agreement was generally modest. CONCLUSIONS: These findings provide preliminary support for the clinical utility of the YI-4 for symptom assessment in referred youths.