Switching from oral extended-release methylphenidate to the methylphenidate transdermal system: continued attention-deficit/hyperactivity disorder symptom control and tolerability after abrupt conversion.

OBJECTIVE: To evaluate symptom control and tolerability after abrupt conversion from oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: In a 4-week, prospective, multisite, open-label study, 171 children (164 intent-to-treat) with diagnosed ADHD aged 6-12 years abruptly switched from a stable dose of oral ER-MPH to MTS in nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. After the first week on the scheduled dose, the dose was titrated to optimal effect. The primary effectiveness outcome was the change from baseline (while taking ER-MPH) to week 4 in ADHD-Rating Scale-IV (ADHD-RS-IV) total scores. Adverse events (AEs) were assessed throughout the study. RESULTS: Most subjects (58%) remained on the initial MTS dose defined by the dose-transition schedule; 38% increased and 4% decreased their MTS dose for optimization. MTS dose optimization resulted in significantly better ADHD-RS-IV total (mean +/- SD) scores at week 4 than at baseline (9.9 +/- 7.47 vs. 14.1 +/- 7.48; p < 0.0001). The most commonly reported AEs included headache, decreased appetite, insomnia, and upper abdominal pain. Four subjects (2.3%) discontinued because of application site reactions and three discontinued because of other AEs. CONCLUSIONS: Abrupt conversion from a stable dose of oral ER-MPH to MTS was accomplished using a predefined dose-transition schedule without loss of symptom control; however, careful titration to optimal dose is recommended. Most AEs were mild to moderate and, with the exception of application site reactions, were similar to AEs typically observed with oral MPH. Limitations of this study included its open-label sequential design without placebo, which could result in spurious attribution of improvement to the study treatment and precluded superiority determinations of MTS over baseline ER-MPH treatment. The apparent superiority of MTS was likely due to more careful titration and clinical monitoring rather than the product itself. ClinicalTrials.gov: NCT00151983.

A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder.

Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD). Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse order). The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100%) and cocaine users (N = 7; 43.8%). Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses) during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001). MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD). Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse order). The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100 percent) and cocaine users (N = 7; 43.8 percent). Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses) during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001). MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

Alcohol use disorder in adolescents.

Alcohol use and abuse by children and adolescents remains a critical problem for modern developed countries. Although tolerance and public policy for alcohol use varies among Western countries, the use of alcohol and other harmful substances is common among adolescents. The use of alcohol can lead to a variety of negative consequences for youth. The risk for alcohol use and abuse, the acquisition of use behaviors, and development into alcohol use disorders and interventions for such problems should be considered in a comprehensive manner that considers neurobiology, development, and the adolescent's environmental ecology. Although the nature and extent of the alcohol problems between countries may vary, approaches to assessment and treatment from the United States may be useful to clinicians in other countries. This paper presents essential background information for the clinician in order to understand the presentation, risk, prevention and treatment of adolescents with alcohol use problems.

Summary of the practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.

This practice parameter describes treatment with stimulant medication. It uses an evidence-based medicine approach derived from a detailed literature review and expert consultation. Stimulant medications in clinical use include methylphenidate, dextroamphetamine, mixed salts of amphetamine, and pemoline. They carry U.S. Food and Drug Administration indications for the treatment of attention-deficit hyperactivity disorder.

Summary of the practice parameter for the prevention and management of aggressive behavior in child and adolescent psychiatric institutions with special reference to seclusion and restraint.

This parameter reviews the current state of the prevention and management of child and adolescent aggressive behavior in psychiatric institutions, with particular reference to the indications and use of seclusion and restraint. It also presents guidelines that have been developed in response to professional, regulatory, and public concern about the use of restrictive interventions with aggressive patients with regard to personal safety and patient rights. The literature on the use of seclusion, physical restraint, mechanical restraint, and chemical restraint is reviewed, and procedures for carrying out each of these interventions are described. Clinical and regulatory agency perspectives on these interventions are presented. Effectiveness, indications, contraindications, complications, and adverse effects of seclusion and restraint procedures are addressed. Interventions are presented to provide more opportunities to promote patient independence and satisfaction with treatment while diminishing the necessity of using restrictive procedures.

Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and efficacy of OROS MPH in a multicenter, randomized, clinical trial. METHODS: Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward. RESULTS: Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively. CONCLUSIONS: For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS, Concerta.

Fluoxetine in adolescents with major depression and an alcohol use disorder: an open-label trial.

Recently, a first placebo-controlled study of an selective serotonin reuptake inhibitor (SSRI) medication was conducted among a sample of adolescents with major depression by Emslie et al. [Arch. Gen. Psychiatry 54 (1997) 1031.]. That study demonstrated efficacy for fluoxetine vs. placebo for treating adolescents with major depression. However, to date, no studies have been conducted to assess the efficacy of fluoxetine or any other SSRI medication in adolescents with major depression in combination with an alcohol use disorder (AUD). In this study, the authors investigated whether fluoxetine decreases the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD. The authors conducted a 12-week open-label study of fluoxetine (20 mg) in 13 adolescents with current comorbid major depression and an AUD. A significant within-group decrease (improvement) was found for both depressive symptoms and drinking during the course of the study. The fluoxetine was well tolerated during the study. These data suggest promise for fluoxetine for decreasing both the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD.

Dose-response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD.

The effects of methylphenidate on the academic performance and classroom behavior of 45 adolescents with attention deficit hyperactivity disorder were studied. During a 6-week, placebo-controlled medication assessment in the context of a summer treatment program, participants received a double-blind, crossover trial of 3 doses of methylphenidate. Dependent measures included note-taking quality, quiz and worksheet scores, written language usage and productivity, teacher ratings, on-task and disruptive behavior, and homework completion. Group data showed positive effects of methylphenidate on academic measures; however, the greatest benefit came with the lowest dose. Although additional benefit did occur for some participants with higher doses, the largest increment of change usually occurred between the placebo and 10-mg dose. Many adolescents did not experience added benefit with increased dosages, and in some cases they experienced deterioration. Guidelines for assessment of medication effects are discussed.

Methylphenidate dosage for children with ADHD over time under controlled conditions: lessons from the MTA.

OBJECTIVES: To examine the trajectory of methylphenidate (MPH) dosage over time, following a controlled titration, and to ascertain how accurately the titration was able to predict effective long-term treatment in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Using the 14-month-treatment database of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), the outcome of the initial placebo-controlled, double-blind, randomized daily switch titration of MPH was compared with the subsequent maintenance pharmacotherapy. Children received monthly monitoring visits and, when needed, medication adjustments. RESULTS: Of the 198 children for whom MPH was the optimal treatment at titration (mean +/- SD dose: 30.5 +/- 14.2 mg/day), 88% were still taking MPH at the end of maintenance (mean dose 34.4 +/- 13.3 mg/day). Titration-determined dose and end-of-maintenance dose were significantly correlated (r = 0.52-0.68). Children receiving combined pharmacotherapy and behavioral treatment ended maintenance on a lower dose (31.1 +/- 11.7 mg/day) than did children receiving pharmacotherapy only (38.1 +/- 14.2 mg/day). Of the 230 children for whom titration identified an optimal treatment, 17% continued both the assigned medication and dosage throughout maintenance. The mean number of pharmacological changes per child was 2.8 +/- 1.8 (SD), and time to first change was 4.7 months +/- 0.3 (SE). CONCLUSIONS: For most children, initial titration found a dose of MPH in the general range of the effective maintenance dose, but did not prevent the need for subsequent maintenance adjustments. For optimal pharmacological treatment of ADHD, both careful initial titration and ongoing medication management are needed.

Impairment and deportment responses to different methylphenidate doses in children with ADHD: the MTA titration trial.

OBJECTIVE: Results of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were analyzed to determine whether a double-blind, placebo-controlled methylphenidate (MPH) titration trial identified the best MPH dose for each child with attention-deficit/hyperactivity disorder (ADHD). METHOD: Children with ADHD assigned to MTA medication treatment groups (n = 289) underwent a controlled 28-day titration protocol that administered different MPH doses (placebo, low, middle, and high) on successive days. RESULTS: A repeated-measures analysis of variance revealed main effects for MPH dose with greater effects on teacher ratings of impairment and deportment (F3 = 100.6, n = 223, p = .0001; effect sizes 0.8-1.3) than on parent ratings of similar endpoints (F3 = 55.61, n = 253, p = .00001; effect sizes 0.4-0.6). Dose did not interact with period, dose order, comorbid diagnosis, site, or treatment group. CONCLUSIONS: The MTA titration protocol validated the efficacy of weekend MPH dosing and established a total daily dose limit of 35 mg of MPH for children weighing less than 25 kg. It replicated previously reported MPH response rates (77%), distribution of best doses (10-50 mg/day) across subjects, effect sizes on impairment and deportment, as well as dose-related adverse events.

Behavioral versus behavioral and pharmacological treatment in ADHD children attending a summer treatment program.

As part of the behavioral treatment in the Multimodal Treatment Study of Children with ADHD (MTA9), children participated in an intensive summer treatment program (STP). This study examined the differences between 57 children in the combined treatment (Comb) group, who were medicated, and 60 children in the behavioral treatment (Beh) group, who were unmedicated throughout the STP. Comb children were significantly better than Beh on 5 measures: rule following, good sportsmanship, peer negative nominations, and STP teacher posttreatment ratings of inattention/overactivity. Groups did not differ on any of the other 30 measures, and responded similarly to the STP over time. Comparisons to normative data revealed that Comb children were more likely to fall within the normative range on 6 measures. The differences between these results and the main MTA results, in which Comb was always superior to Beh, are discussed in terms of the relative intensity of combined treatments. The implications for future studies of pharmacological and behavioral treatment for ADHD are discussed.

Inter-rater reliability of the SCID alcohol and substance use disorders section among adolescents.

Diagnostic interviews for substance use disorders tend to have high reliability among adults. We examined the inter-rater reliability of the substance use disorders section of the Structured Clinical Interview for the DSM, using 46 male and 25 female adolescent drinkers recruited from community and treatment sources. Inter-rater reliability was high for individual DSM-IV alcohol symptoms (kappa=0.84-1.0) and diagnoses (kappa=0.94), and for other substance use disorder diagnoses (kappa=0.82-1.0).

Disruptive behavior disorders and substance use disorders in adolescents.

Disruptive behaviors disorders in the form of conduct disorder, oppositional defiant disorder and/or attention-deficit hyperactivity disorder are found in a majority of adolescents with substance use disorders These disorders influence the risk for and the course of substance use disorders in adolescents and potentially provide important targets for intervention. Interventions such as family therapy and multisystemic therapy can focus on important environmental factors that help to produce and sustain substance use, related problems and disruptive/deviant social behavior. Researchers and clinicians are increasingly utilizing multimodal approaches that use several psychosocial approaches in addition to medication, if indicated. This article reviews our current understanding of the relationship between disruptive behavior disorders and substance use disorders in adolescents and the importance of this understanding in the prevention, assessment and treatment of adolescents with substance use disorders.

Methylphenidate and behavior modification in children with ADHD and comorbid ODD or CD: main and incremental effects across settings.

OBJECTIVE: Although the combination of methylphenidate (MPH) and behavior modification (BMOD) has been advocated to enhance clinical outcome for children with attention-deficit hyperactivity disorder (ADHD) and comorbid disruptive disorders, few group studies have been conducted. This study evaluates the separate and incremental effects of these modalities on rating scale and observational measures in multiple settings. METHOD: Sixteen of 22 children with ADHD and comorbid disruptive disorder completed a randomized, placebo-controlled study examining the separate and incremental effects of 2 doses of MPH and BMOD during a partial hospitalization program. Of the 6 who did not complete the study, 2 children developed significant side effects. For the 16 who did complete the study, effects were examined on measures of symptom ratings, behavioral frequencies, and stimulant side effects across program activities. RESULTS: Based on alpha-adjusted analyses of variance, there were several main effects of MPH and BMOD on ADHD symptoms, oppositional behavior, and positive social behavior, with certain effects unique to each intervention and setting. One incremental effect each was found for MPH (positive mood/behavior) and BMOD (negative behavior). MPH and BMOD were associated with few side effects. Effect sizes for each intervention showed considerable variability in clinical response. CONCLUSIONS: That MPH and BMOD had certain unique main and incremental effects extends findings supporting their combination and suggests that integrated studies evaluate multiple dimensions of functioning and in novel settings (e.g., home, school). The incorporation of other intervention components in combined treatments may be warranted to enhance clinical efficacy.

Effects of methylphenidate on aggressive urban children with attention deficit hyperactivity disorder.

Determined the efficacy of methylphenidate (MPH) in a clinical population of aggressive, urban children diagnosed with attention deficit hyperactivity disorder (ADHD). In previous studies of prepubertal children with ADHD, MPH has been shown to be effective when compared with placebo. Eighteen inner-city children (ages 6 to 12 years), diagnosed with ADHD and attending a summer treatment program for youth with disruptive behavior disorders, participated in a double-blind placebo trial with assessment data obtained from staff in the program and parents at home. Based on staff ratings of the children's behavior in the program and an academic classroom, the children displayed significant improvements in ADHD symptoms and aggressive behavior with low- and high-dose MPH conditions. At home, parents and guardians reported few significant differences between placebo and MPH on behavior ratings. In both settings, MPH was well tolerated with few side effects found during active drug conditions.

Psychopathology in adolescent alcohol abuse and dependence.

Adolescents who abuse or are dependent on alcohol often have coexisting mental disorders. These disorders may both precipitate alcohol use disorders and result from them. In addition, both types of disorders may arise independently in adolescents at high risk. Mental disorders that commonly co-occur with alcohol use disorders in adolescents include antisocial disorders, mood disorders, and anxiety disorders. Treatment programs for adolescents with alcohol use disorders should seek not only to eliminate alcohol and other drug use but also to improve the symptoms of other mental disorders.

Practice parameters for the assessment and treatment of children and adolescents with substance use disorders. American Academy of Child and Adolescent Psychiatry.

These practice parameters describe the assessment and treatment of children and adolescents with substance use disorders and are based on scientific evidence regarding diagnosis and effective treatment as well as on the current state of clinical practice. Given the paucity of research on the treatment of substance use disorders in children and adolescents, many of the recommendations are drawn from the adult literature and current clinical practice. These parameters consider risk factors for substance use and related problems, normative use of substances by adolescents, the comorbidity of substance use disorders with other psychiatric disorders, and treatment settings and modalities.

Gender and comorbid psychopathology in adolescents with alcohol dependence.

OBJECTIVE: Although several mental disorders have been shown to be common in adolescents with substance use disorders, prior studies have not specifically focused on alcohol dependence and have not had sufficient sample sizes to examine gender effects. This study contrasts mental disorder diagnoses and symptoms between a sample of adolescents with alcohol dependence and a community control sample of adolescents and incorporates gender analyses. METHOD: Adolescents (aged 14 years 0 months to 18 years 0 months) with alcohol dependence (females: n = 55; males: n = 78) and community-dwelling control adolescents without substance use disorders (females: n = 44; males: n = 42) were assessed by means of a semistructured interview for DSM-III-R. RESULTS: While cannabis and hallucinogen use disorders were common in the alcohol dependence group, females and males had similar rates. Conduct disorder (CD), oppositional defiant disorder, attention-deficit hyperactivity disorder, major depression (MD), and posttraumatic stress disorder (PTSD) had significantly higher rates in the alcohol dependence than in the community control group. Depression and PTSD symptoms were more strongly associated with alcohol dependence in females than in males. A configural frequency analysis showed that CD and MD tended to occur together in both female and male adolescents with alcohol dependence. CONCLUSIONS: While alcohol-dependent females and males similarly exhibited more comorbid disorders than control adolescents, gender affects the relationship of alcohol dependence to MD and PTSD. Rather than reflecting distinct types, the comorbid disorders of CD and MD jointly characterize many adolescents with alcohol dependence.

Patterns of DSM-IV alcohol abuse and dependence symptoms in adolescent drinkers.

OBJECTIVE: Diagnostic criteria for alcohol use disorders have largely been developed from research and clinical experience with adults. This research was designed to describe patterns of DSM-IV alcohol use disorder symptoms, and other problem domains, in adolescents with alcohol problems. METHOD: A modified version of the Structured Clinical Interview for the DSM (SCID) was used to assess DSM-IV alcohol abuse and alcohol dependence symptoms in 91 male and 90 female adolescent drinkers with various levels of alcohol consumption and alcohol-related problems. The SCID was expanded to assess other alcohol problem domains thought to be relevant for adolescents. RESULTS: DSM-IV dependence symptoms showed moderate to high covariation, supporting the utility of the alcohol dependence construct in adolescence. Compared to previous reports from adult samples, some symptoms were relatively infrequent (e.g., withdrawal, medical problems). Tolerance had low specificity for the diagnosis of alcohol dependence. There was significant heterogeneity in the symptomatology of subjects with DSM-IV alcohol abuse. Although they are not in the DSM-IV criteria, alcohol-related blackouts, craving and risky sexual behavior were common in adolescents with DSM-IV alcohol dependence and abuse diagnoses. CONCLUSIONS: The data generally support the utility of DSM-IV criteria for alcohol dependence among adolescents. However, tolerance, withdrawal and medical problems appear to present differently in adolescents than has been reported in adults. Those with DSM-IV alcohol abuse diagnoses had very heterogeneous patterns of symptomatology, suggesting limitations of the criteria for DSM-IV alcohol abuse in adolescence. Alcohol-related blackouts, craving and risky sexual behavior are common among adolescents with alcohol use disorders and are an important focus for assessment and treatment efforts.