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.

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.

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.