Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures.

BACKGROUND: Methylphenidate has been shown elsewhere to improve hyperactivity in about half of treated children who have pervasive developmental disorders (PDD) and significant hyperactive-inattentive symptoms. We present secondary analyses to better define the scope of effects of methylphenidate on symptoms that define attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), as well as the core autistic symptom domain of repetitive behavior. METHODS: Sixty-six children (mean age 7.5 y) with autistic disorder, Asperger's disorder, and PDD not otherwise specified, were randomized to varying sequences of placebo and three different doses of methylphenidate during a 4-week blinded, crossover study. Methylphenidate doses used approximated .125, .25, and .5 mg/kg per dose, twice daily, with an additional half-dose in the late afternoon. Outcome measures included the Swanson, Nolan, and Pelham Questionnaire revised for DSM-IV (ADHD and ODD scales) and the Children's Yale-Brown Obsessive Compulsive Scales for PDD. RESULTS: Methylphenidate was associated with significant improvement that was most evident at the .25- and .5-mg/kg doses. Hyperactivity and impulsivity improved more than inattention. There were not significant effects on ODD or stereotyped and repetitive behavior. CONCLUSIONS: Convergent evidence from different assessments and raters confirms methylphenidate's efficacy in relieving ADHD symptoms in some children with PDD. Optimal dose analyses suggested significant interindividual variability in dose response.

Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

OBJECTIVE: The purpose of this study was to examine the effects of methylphenidate (MPH) on functional outcomes, including children's social skills, classroom behavior, emotional status, and parenting stress, during the 4-week, double-blind placebo controlled phase of the Preschoolers with Attention Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS). METHODS: A total of 114 preschoolers who had improved with acute MPH treatment, were randomized to their best MPH dose (M = 14.22 mg/day; n = 63) or placebo (PL; n = 51). Assessments included the Clinical Global Impression-Severity (CGI-S), parent and teacher versions of the Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale (SCS), Social Skills Rating System (SSRS), and Early Childhood Inventory (ECI), and Parenting Stress Index (PSI). RESULTS: Medication effects varied by informant and outcome measure. Parent measures and teacher SWAN scores did not differentially improve with MPH. Parent-rated depression (p < 0.02) and dysthymia (p < 0.001) on the ECI worsened with MPH, but scores were not in the clinical range. Significant medication effects were found on clinician CGI-S (p < 0.0001) and teacher social competence ratings (SCS, p < 0.03). CONCLUSIONS: Preschoolers with ADHD treated with MPH for 4 weeks improve in some aspects of functioning. Additional improvements might require longer treatment, higher doses, and/or intensive behavioral treatment in combination with medication.

Effectiveness of methylphenidate in the 10-month continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

OBJECTIVE: The aim of this study was to examine immediate-release methylphenidate effectiveness during the 10-month open-label continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS). METHODS: One hundred and forty preschoolers with ADHD, who had improved with acute immediate-release methylphenidate (IR-MPH) treatment, entered a 10-month, open-label medication maintenance at six sites. Assessments included the Clinical Global Impression-Severity (CGI-S), CGI-Improvement (CGI-I), Children's Global Assessment Scale (C-GAS), Swanson, Nolan, and Pelham Questionnaire (SNAP), Scale Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale, Social Skills Rating System (SSRS), and Parenting Stress Index-Short Form (PSI-SF). RESULTS: For the 95 children who completed the 10-month treatment, improvement occurred on the CGI-S (p = 0.02), CGI-I (p < 0.01), C-GAS (p = 0.001), and SSRS (p = 0.01). SNAP and SWAN scores remained stable. Forty five children discontinued: 7 for adverse effects, 7 for behavior worsening, 7 for switching to long-acting stimulants, 3 for inadequate benefit, and 21 for other reasons. The mean MPH dose increased from 14.04 mg/day +/- SD 7.57 (0.71 +/- 0.38 mg/kg per day) at month 1 to 19.98 mg/day +/- 9.56 (0.92 +/- 0.40 mg/kg per day) at month 10. CONCLUSIONS: With careful monitoring and gradual medication dose increase, most preschoolers with ADHD maintained improvement during long-term IR-MPH treatment. There was substantial variability in effective and tolerated dosing.

Factor structure of parent- and teacher-rated attention-deficit/hyperactivity disorder symptoms in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

OBJECTIVE: This study examines one-, two-, and three-factor models of attention-deficit/hyperactivity disorder (ADHD) using the existing 18 Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV) symptoms in a sample of symptomatic preschoolers. METHODS: Parent and/or teacher ratings of DSM-IV symptoms were obtained for 532 children (aged 3-5.5) who were screened for the Preschool ADHD Treatment Study (PATS). Confirmatory factor analysis (CFA) using symptoms identified on the Conners' Parent and Teacher Rating Scales was conducted to assess a two-factor model representing the DSM-IV dimensions of inattention (IN) and hyperactivity/impulsivity (H/I), a three-factor model reflecting inattention, hyperactivity, and impulsivity, and a single-factor model of all ADHD symptoms. Exploratory factor analysis (EFA) was subsequently used to examine the latent structure of the data. RESULTS: For parent ratings, the two-factor and three-factor models were marginally acceptable according to several widely used fit indices, whereas the one-factor model failed to meet minimum thresholds for goodness-of-fit. For teachers, none of the models was a solid fit for the data. Maximum likelihood EFAs resulted in satisfactory two and three-factor models for both parents and teachers, although all models contained several moderate cross loadings. Factor loadings were generally concordant with those published for older children and community-based samples. CONCLUSION: ADHD subtypes according to current DSM-IV specifications may not be the best descriptors of the disorder in the preschool age group.

Parent versus teacher ratings of attention-deficit/hyperactivity disorder symptoms in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

OBJECTIVE: To assess parent-teacher concordance on ratings of DSM-IV symptoms of attention-deficit/hyperactivity disorder (ADHD) in a sample of preschool children referred for an ADHD treatment study. METHODS: Parent and teacher symptom ratings were compared for 452 children aged 3-5 years. Agreement was calculated using Pearson correlations, Cohen's kappa, and conditional probabilities. RESULTS: The correlations between parent and teacher ratings were low for both Inattentive (r = .24) and Hyperactive-Impulsive (r = .26) symptom domains, with individual symptoms ranging from .01-.28. Kappa values for specific symptoms were even lower. Conditional probabilities suggest that teachers are only moderately likely to agree with parents on the presence or absence of symptoms. Parents were quite likely to agree with teachers' endorsement of symptoms, but much less likely to agree when teachers indicated that a symptom was not present. CONCLUSIONS: Results provide important data regarding base rates and concordance rates in this age group and support the hypothesis that preschool-aged children at risk for ADHD exhibit significant differences in behavior patterns across settings. Obtaining ratings from multiple informants is therefore considered critical for obtaining a full picture of young children's functioning.

Clinical presentation of attention-deficit/hyperactivity disorder in preschool children: the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

OBJECTIVE: The aim of this study was to describe the clinical presentation of preschoolers diagnosed with moderate to severe attention-deficit/hyperactivity disorder (ADHD) recruited for the multisite Preschool ADHD Treatment Study (PATS). The diagnosis and evaluation process will also be described. METHOD: A comprehensive multidimensional, multi-informant assessment protocol was implemented including the semistructured PATS Diagnostic Interview. Parent and teacher-report measures were used to supplement information from interviews. Consensus agreement by a cross-site panel on each participant's diagnoses was required. Analyses were conducted to describe the sample and to test associations between ADHD severity and demographic and clinical variables. RESULTS: The assessment protocol identified 303 preschoolers (3-5.5 years) with moderate to severe ADHD Hyperactive/Impulsive or Combined type. The majority of participants (n = 211, 69.6%) experienced co-morbid disorders, with oppositional defiant disorder, communication disorders, and anxiety disorders being the most common. Participants with co-morbid communication disorders were found to be more anxious and depressed. ADHD severity was found to correlate with more internalizing difficulties and lower functioning. Although boys and girls had similar symptom presentations, younger children had significantly higher ADHD severity. CONCLUSIONS: Preschoolers with moderate to severe ADHD experience high co-morbidity and impairment, which have implications for both assessment and treatment.

Comorbidity moderates response to methylphenidate in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

OBJECTIVE: The aim of this study was to examine whether demographic or pretreatment clinical and social characteristics influenced the response to methylphenidate (MPH) in the Preschoolers with ADHD Treatment Study (PATS). METHODS: Exploratory moderator analyses were conducted on the efficacy data from the PATS 5-week, double-blind, placebo-controlled six-site titration trial. Children (N = 165, age 3-5.5 years) were randomized to 1 week each of four MPH doses (1.25, 2.5, 5, and 7.5 mg) and placebo administered three times per day (t.i.d.). We assessed the fixed effects on the average slope in the regression outcome on moderators, weight-adjusted dose, and the moderator-by-dose interaction using SAS PROC GENMOD. RESULTS: A significant interaction effect was found for a number of co-morbid disorders diagnosed in the preschoolers at baseline (p = 0.005). Preschoolers with three or more co-morbid disorders did not respond to MPH (Cohen's d at 7.5 mg dose relative to placebo = -0.37) compared to a significant response in the preschoolers with 0, 1, or 2 co-morbid disorders (Cohen's d = 0.89, 1.00, and 0.56, respectively). Preschoolers with more co-morbidity were found to have more family adversity. No significant interaction effect was found with the other variables. CONCLUSIONS: In preschoolers with ADHD, the presence of no or one co-morbid disorder (primarily oppositional defiant disorder) predicted a large treatment response at the same level as has been found in school-aged children, and two co-morbid disorders predicted moderate treatment response; whereas the presence of three or more co-morbid disorders predicted no treatment response to MPH.

Safety and tolerability of methylphenidate in preschool children with ADHD.

OBJECTIVE: To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD) during 1 year of treatment. METHOD: Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n=183); a 5-week placebo-controlled, double-blind phase (n=165); a 5-week double-blind, parallel phase (n=114); and 10 months of open-label maintenance (n=140 entered, 95 completed). Mean total daily MPH doses rose from the titration trial best dose, 14.1 (+/-8.1) mg/day, to 20.5 (+/-9.7) mg/day mean total daily dose at the end of maintenance. Pulse, blood pressure, and the presence of treatment emergent adverse events (AEs), parent and teacher AE ratings, and vital signs were recorded in each phase. RESULTS: Thirty percent of parents spontaneously reported moderate to severe AEs in all study phases after baseline. These included emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts, appetite decrease, and irritability. During titration, decreased appetite (chi=5.4, p<.03), trouble sleeping (chi=5.4, p<.03), and weight loss (chi=4.0, p<.05) occurred statistically more often on MPH than on placebo. During maintenance, trouble sleeping and appetite loss persisted and other MPH-related AEs decreased. There were transient, one-time pulse and blood pressure elevations in five children. Twenty-one children (11%) discontinued because of drug-attributed AEs. CONCLUSIONS: Eleven percent of preschoolers discontinued treatment because of intolerable MPH AEs. Of the serious AEs reported, one occurred in baseline, two in lead-in, three in titration, one in parallel, and one in maintenance. Only one was possibly related to MPH.

Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD.

OBJECTIVE: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). METHOD: The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale. RESULTS: Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001) t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the preschoolers (n=114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD. CONCLUSIONS: MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication.

Stimulant-related reductions of growth rates in the PATS.

OBJECTIVE: To investigate growth of children with attention-deficit/hyperactivity disorder (ADHD) in the Preschool ADHD Treatment Study (PATS) before and after initiation of treatment with methylphenidate at titrated doses (average, 14.2 mg/day) administered three times daily, 7 days/week for asymptotically equal to1 year. METHOD: The heights and weights of 140 children with ADHD were measured up to 29 times in the PATS protocol, starting at an average age of 4.4 years. The relationship between standard (z) scores and time on medication was examined using mixed-effect regression to estimate change in relative size (slope). RESULTS: Average relative size at baseline was significantly (p<.0001) greater than zero for z height (+0.45) and z weight (+0.78), indicating greater than expected height (by 2.04 cm) and weight (by 1.78 kg). During treatment, slopes were significantly (p<.0001) less than zero for z height (-0.304/yr) and z weight (-0.530/yr), indicating reduction of growth rates. For 95 children who remained on medication, annual growth rates were 20.3% less than expected for height (5.41 cm/yr-6.79 cm/yr=-1.38 cm/yr) and 55.2% for weight (1.07 kg/yr-2.39 kg/yr=-1.32 kg/yr). CONCLUSIONS: Risks of reduced growth rates should be balanced against expected benefits when preschool-age children are treated with stimulant medication.

Pharmacogenetics of methylphenidate response in preschoolers with ADHD.

OBJECTIVE: The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHOD: DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers completed ADHD symptom scales and side effect ratings for each of five randomly administered weekly conditions that included immediate-release methylphenidate 1.25, 2.5, 5.0, 7.5 mg and placebo given three times daily. Candidate genes hypothesized to influence stimulant effects or individual risks for ADHD were genotyped. RESULTS: Although the primary analysis did not indicate significant genetic effects, secondary analyses revealed associations between symptom response and variants at the dopamine receptor (DRD4) promoter (p=.05) and synaptosomal-associated protein 25 (SNAP25) allelesT1065G (p=.03) andT1069C (p=.05). SNAP25 variants were also associated with tics (p=.02), buccal-lingual movements (p=.01), and irritability (p=04). DRD4 variants were also associated with picking (p=.03). Increasing dose predicted irritability (p=.05) and social withdrawal (p=.03) with DRD4 variants. There were no significant effects for the dopamine transporter (DAT1). CONCLUSIONS: Emerging evidence suggests the potential for understanding the individual variability of response to and side effects of ADHD medications from the study of genetics, although additional research is required before these findings are proven to have clinical utility.

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. CONCLUSIONS: Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

Acute and long-term safety and tolerability of risperidone in children with autism.

Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

Eating disorder and depressive symptoms in urban high school girls from different ethnic backgrounds.

This study examined ethnic group differences in the rates of eating disorder symptoms (EDS) and depressive disorder symptoms (DDS) with respect to ethnic identity, relative body weight, and abnormal eating behaviors among adolescent girls. A district-wide sample of high school girls (N = 1445) from different ethnic backgrounds was surveyed. EDS were assessed with the Eating Attitudes Test-26, abnormal eating behaviors with the Eating Behaviors Survey, and DDS with the Short Mood and Feelings Questionnaire. Two dimensions of ethnic identity, ethnic identity achievement and other group orientation, were assessed with Multi-Group Ethnic Identity Measure. Hispanic and non-Hispanic white girls had the highest and African-American (AA) and Caribbean girls the lowest rates of EDS. Asian girls reported the highest and AA girls the lowest rates of DDS. Early dieting was associated with EDS and DDS in Caribbean, non-Hispanic white, and mixed background girls. Relative body weight was related to EDS in all ethnic groups except in non-Hispanic white and mixed background girls. The authors did not find an effect of ethnic identity achievement on psychopathology, but there was an effect of other group orientation on both EDS and DDS. Clinicians should inquire about EDS and DDS in girls of all ethnic groups. Prevention efforts to delay unsupervised dieting may protect adolescent girls from the development of EDS and DDS.

Weight and leptin changes among risperidone-treated youths with autism: 6-month prospective data.

OBJECTIVE: The authors examined the developmental impact and temporal characteristics of risperidone-associated weight change. METHOD: Weight change was measured for 63 children and adolescents with autism treated with risperidone for 6 months. Change in serum leptin levels after 2 months was examined as a predictor of final weight gain in mixed regression models that controlled for site, gender, age, and risperidone dose. RESULTS: Age- and gender-standardized weight increased after 6 months of treatment (gross: mean=5.6 kg [SD=3.9]; standardized: mean=0.6 z [SD=0.5]) and was positively correlated with weight gained after 1 month. Change in leptin levels after 2 months of treatment (mean=-0.3 ng/ml, SD=6.2) (N=48) did not predict final weight gain. CONCLUSIONS: Chronic risperidone exposure in children with autism causes weight gain in excess of developmentally expected norms that follows a curvilinear trajectory and decelerates over time. Serum leptin change does not reliably predict risperidone-associated weight gain.

Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology.

OBJECTIVE: To improve the gathering of adverse events (AEs) in pediatric psychopharmacology by examining the value and acceptability of increasingly detailed elicitation methods. METHOD: Trained clinicians administered the Safety Monitoring Uniform Report Form (SMURF) to 59 parents and outpatients (mean age +/- SD = 11.9 +/- 3.2 years) in treatment, with 36% on stimulants, 29% on selective serotonin reuptake inhibitor drugs, 10% on both, and 25% on other drug combinations. The SMURF included a brief general inquiry, a drug-specific inquiry, and a comprehensive body system review (BSR). RESULTS: SMURF administration took 24.6 +/- 13.9 minutes (median, 21). The BSR took 15.5 +/- 8.1 minutes (median, 14) longer (p < .0001) than the general inquiry (4.3 +/- 5.4 minutes) and the drug-specific inquiry (4.2 +/- 2.9 minutes). The general inquiry elicited 48 AEs, the drug-specific inquiry elicited 16 additional AEs, and the BSR 129 additional AEs. Of all the clinically relevant AEs elicited by the SMURF (n = 36), 19 (53%) were elicited by the BSR. The BSR length and detail were acceptable to parents but not to clinicians. CONCLUSIONS: The BSR elicited additional clinically significant AEs that had been missed with less detailed methods. Parents, but not clinicians, rated satisfaction and acceptability of the BSR as good.

Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials.

OBJECTIVE: A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales. METHOD: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data. RESULTS: The most common symptoms identified by parents were tantrums, aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom category, largest for self-injury (2.11) and tantrums (1.95). CONCLUSIONS: Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior. Rating individualized participant-chosen target symptoms seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect and might have clinical application.

Socioeconomic status as a moderator of ADHD treatment outcomes.

OBJECTIVE: To explore whether socioeconomic status (SES) variables moderate treatment response of attention-deficit/hyperactivity disorder (ADHD) to medication management (MedMgt), behavioral treatment (Beh), combined intervention (Comb), and routine community care (CC). METHOD: The MTA Cooperative Group's intent-to-treat (ITT) analyses were repeated, covarying for composite Hollingshead SES, education, occupation, income, and marital status. RESULTS: Individual SES variables were more informative than the composite Hollingshead Index. Treatment response of children from less educated households paralleled ITT outcomes: no significant difference was found between Comb and MedMgt (both better than Beh and CC) for core ADHD symptoms. However, children from more educated families showed superior reduction of ADHD symptoms with Comb. For oppositional-aggressive symptoms, children from blue-collar, lower SES households benefited most from Comb, whereas those from white-collar, higher SES homes generally showed no differential treatment response. Household income and marital status failed to influence outcomes. Controlling for treatment attendance attenuated the moderating effects of the SES variables only for MedMgt. CONCLUSIONS: Investigators are encouraged to use independent SES variables for maximal explanation of SES effects. Clinicians should prioritize target symptoms and consider the mediating role of treatment adherence when determining an ADHD patient's optimal intervention plan.

Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial.

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.

Nine months of multicomponent behavioral treatment for ADHD and effectiveness of MTA fading procedures.

We examined 9-month data from the 14-month NIMH Multimodal Treatment Study of Children with ADHD (the MTA) as a further check on the relative effect of medication (MedMgt) and behavioral treatment (Beh) for attention-deficit/hyperactivity disorder (ADHD) while Beh was still being delivered at greater intensity than at 14-month endpoint, and conversely as a check on the efficacy of the MTA behavioral generalization/maintenance procedures. Intention-to-treat analysis at 9 months showed essentially the same results as at 14 months, after Beh had been completely faded; MedMgt and the combination (Comb) of medication and Beh were significantly superior to Beh and community care (CC) for ADHD and oppositional-defiant (ODD) symptoms, with mixed results for social skills and internalizing symptoms. All treatment-group differences examined as changes in slopes from 9 to 14 months were nonsignificant (we found general improvement for all groups). Slopes from baseline to 9 months correlated highly (r > .74, p < .0001) with slopes from baseline to 14 months for all groups. The time function from baseline to 14 months showed a significant linear, but not quadratic, trend for the main outcome measure (a composite of parent- and teacher-rated ADHD and ODD symptoms) for all groups. Findings suggest that in contrast to the hypothesized deterioration in the relative benefit of Beh between 9 and 14 months (after completion of fading), the MTA Beh generalization and maintenance procedures implemented through 9 months apparently yielded continuing improvement through 14 months, with preservation of the relative position of Beh compared to other treatment strategies.