The treatment of severe child aggression (TOSCA) study: Design challenges

<p>Abstract</p> <p>Background</p> <p>Polypharmacy (the concurrent use of more than one psychoactive drug) and other combination interventions are increasingly common for treatment of severe psychiatric problems only partly responsive to monotherapy. This practice and research on it raise scientific, clinical, and ethical issues such as additive side effects, interactions, threshold for adding second drug, appropriate target measures, and (for studies) timing of randomization. One challenging area for treatment is severe child aggression. Commonly-used medications, often in combination, include psychostimulants, antipsychotics, mood stabilizers, and alpha-2 agonists, which vary considerably in terms of perceived safety and efficacy.</p> <p>Results</p> <p>In designing our NIMH-funded trial of polypharmacy, we focused attention on the added benefit of a second drug (risperidone) to the effect of the first (stimulant). We selected these two drugs because their associated adverse events might neutralize each other (e.g., sleep delay and appetite decrease from stimulant versus sedation and appetite increase from antipsychotic). Moreover, there was considerable evidence of efficacy for each drug individually for the management of ADHD and child aggression. The study sample comprised children (ages 6-12 years) with both diagnosed ADHD and disruptive behavior disorder (oppositional-defiant or conduct disorder) accompanied by severe physical aggression. In a staged sequence, the medication with the least problematic adverse effects (stimulant) was openly titrated in 3 weeks to optimal effect. Participants whose behavioral symptoms were not normalized received additional double-blind medication, either risperidone or placebo, by random assignment. Thus children whose behavioral symptoms were normalized with stimulant medication were not exposed to an antipsychotic. All families participated in an empirically-supported parent training program for disruptive behavior, so that the actual comparison was stimulant+parent training versus stimulant+antipsychotic+parent training.</p> <p>Conclusions</p> <p>We hope that the resolutions of the challenges presented here will be useful to other investigators and facilitate much-needed research on child psychiatric polypharmacy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00796302">NCT00796302</a></p

Does switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?

Background: To evaluate health-related quality of life (HRQL) and medication satisfaction after switching from a stable dose of 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, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population) aged 6-12 years diagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dose was then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C), a disease-specific validated HRQL survey instrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children and their families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS) at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative). Tolerability was monitored by spontaneous adverse event (AE) reporting. Results: AIM-C child and family HRQL mean scores were above the median possible score at baseline and were further improved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economic impact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the study medication. The majority of treatment-emergent AEs (> 98%) were mild to moderate in intensity, and the most commonly reported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study due to intolerable AEs (n = 3) and application site reactions (n = 4). Conclusion: This study demonstrates that MTS, when carefully titrated to optimal dose, may further improve child and family HRQL, as well as behavioral, medication worry, and economic impact item scores, as measured by the AIM-C in subjects switching to MTS from a stable dose of routinely prescribed oral ER-MPH after a short treatment period. Furthermore, following the abrupt conversion from oral ER-MPH to MTS, the majority of caregivers reported being highly satisfied with MTS as a treatment option for their children with ADHD. Trial Registration: NCT0015198

Practice Parameter for the Assessment and Treatment of Children and Adolescents With Substance Use Disorders

This practice parameter describes the assessment and treatment of children and adolescents with substance use disorders and is based on scientific evidence and clinical consensus regarding diagnosis and effective treatment as well as on the current state of clinical practice. This parameter considers 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

Alcohol and psychiatric comorbidity

Comorbid psychiatric disorders and drug use disorders (DUDs) are common among alcoholics (Regier, Farmer, Rae, Locke, Keith, Judd, & Goodwin, 1990; Kessler, McGonagle, Zhao, Nelson, Hughes, Eshleman, Wittchen, & Kendler, 1994). These comorbid disorders often predict a shorter time to relapse of alcoholism (Greenfield, Weiss, Muenz, Vagge, Kelly, Bello, & Michael, 1998). However, despite the prevalence and the adverse effects of this comorbidity, few controlled treatment studies have been conducted involving this dual diagnosis population (Litten & Allen, 1999). To date, most of these few studies of alcoholics with comorbid disorders have been restricted to studies of alcoholics with either comorbid major depression or comorbid anxiety disorders (Litten & Allen, 1995). The results of these trials suggest efficacy for SSRI antidepressants and tricyclic antidepressants for treating alcoholics with comorbid major depression and suggest efficacy for buspirone for treating alcoholics with comorbid anxiety disorders (Mason, Kocsis, Ritvo, & Cutler, 1996; Cornelius, Salloum, Ehler, Jarrett, Cornelius, Perel, Thase, & Black, 1997; Kranzler, Burleson, Del Boca, Babor, Korner, Brown, & Bohn, 1994). However, controlled treatment studies involving alcoholics with other comorbid disorders are almost totally lacking. Consequently, to date, no empirically proven treatment exists for most of these comorbid disorders

Cognitive Distortions and Psychiatric Diagnosis in Dually Diagnosed Adolescents

Objective The purpose of this study was to examine the characteristics and patterns of cognitive distortions among psychiatrically hospitalized adolescents. Method Measures of cognitive distortions, depression, and hopelessness were administered to 135 adolescents on two psychiatric inpatient units. Subjects were grouped according to their Axis I diagnoses: depression only, conduct disorder only, depression and substance abuse, conduct disorder and substance abuse, all three diagnoses, and none of the three diagnoses. Results Multivariate analyses of covariance indicated that differently diagnosed adolescents exhibited varying levels of cognitive distorting as measured by the Children\u27s Negative Cognitive Errors Questionnaire (CNCEQ). In particular, adolescents with multiple Axis I diagnoses tended to score highest. On all but one of four CNCEQ subscales, the depression only group evidenced as much cognitive distortion as did the group with multiple diagnoses. However, each diagnostic grouping demonstrated its own somewhat distinct distortions based on CNCEQ subscales. Conclusions Findings are discussed in terms of the utility of differentiating cognitive styles for subsequent treatment. It is suggested that disparate cognitive interventions could be matched with adolescents displaying particular problems