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Biomedical subjects

L L Greenhill

Publications and source records attributed to L L Greenhill.

At least 19 recordsLinked to original sources

Analog classroom assessment of Adderall in children with ADHD.

OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.

Adolescent

Assessment issues in treatment research of pediatric anxiety disorders: what is working, what is not working, what is missing, and what needs improvement.

Reviewing the strengths and weaknesses of the rating scales for anxiety disorders makes it possible to select appropriate measures for use in a multisite treatment study of children and adolescents with DSM-IV-diagnosed anxiety disorders. Categorical diagnosis for study inclusion is provided by the K-SADS-PL, which has strong published psychometrics for anxiety disorders. Broadband symptom ratings of diverse pediatric psychiatric disorder can be obtained at baseline by the parent-scored Child Behavior Checklist. Anxiety symptom monitoring may be provided by the use of two psychometrically strong self-report measures, the MASC and the SCARED. Weekly global ratings are provided by the CGI whose scale points have been enhanced by detailed anchors; in addition, the raters all trained on practice vignettes to calibrate their scoring. Clinician-based ratings of the patient's anxiety symptoms can be carried out in adolescent patients using the HAM-A. The newly developed Children's Anxiety Rating Scale promises to cover the full pediatric age range as a clinician-based anxiety rating instrument, but must first be subjected to formal psychometric and treatment sensitivity evaluation.

Anxiety Disorders

National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices.

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.

Attention Deficit Disorder with Hyperactivity

Management of suicidal behavior in children and adolescents.

Many therapeutic approaches to managing suicidal behavior among youth have been used, including in-school education programs, screening programs, telephone hotlines, cognitive behavioral therapies, medication management, and inpatient milieux treatment programs. These interventions have been applied based on educational and therapeutic principles drawn from prior work with adolescents in varied scholastic and psychiatric settings. This article reviews: the assessment of risk factors among suicide attempters, emotional states, family, social isolation, interpersonal loss, substance and alcohol abuse, and treatment strategies.

Adolescent

Manual development for the treatment of child and adolescent disorders.

There has been a proliferation of treatment manuals in the past decade as part of an effort to operationalize treatment applications and standardize treatments across subjects, settings, and therapists. In this article we present the essential elements needed to develop manuals for the psychosocial and psychopharmacological treatments of child and adolescent disorders, using one modality or in multimodal treatment trials. We delineate how to integrate various treatment components for psychosocial and psychopharmacological manuals, as well as those for control conditions. We also examine the therapist variable as it concerns training and adherence to the structured or flexible scripted manuals. Finally, we discuss the advantages and disadvantages of manuals in terms of how they may affect outcome, recommending that treatments be both empirically grounded and clinically meaningful.

Adolescent

Medication treatment strategies in the MTA Study: relevance to clinicians and researchers.

OBJECTIVE: Clinicians have difficulty applying drug research findings to clinical practice, because research protocols use methods different from those used in daily office practice settings. METHOD: To design a medication protocol for a multisite clinical trial involving 576 children with attention-deficit hyperactivity disorder (ADHD) while maintaining relevance to clinical practice, investigators from the NIMH Collaborative Multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA study) developed novel medication strategies. These were designed to work either in a monomodal or multimodal format and to ensure standard approaches are used across diverse sites. Each child randomized to medication (projected N = 288) is individually titrated to his or her "best" methylphenidate dose and has individual ADHD symptoms monitored. Decision rules were developed to guide "best dose" selection, dose changes, medication changes, the management of side effects, and integration with psychosocial treatments. CONCLUSIONS: The MTA study uses a controlled method to standardize the identification of each child's "best" methylphenidate dose in a national, multisite cooperative treatment program. Although the titration protocol is complex, the study's individual dosing approach and algorithms for openly managing ADHD children's medication over time will be of interest to clinicians in office practice.

Adolescent

NIMH collaborative multisite multimodal treatment study of children with ADHD: I. Background and rationale.

OBJECTIVE: The National Institute of Mental Health's recently initiated 5-year, multisite, multimodal treatment study of children with attention-deficit hyperactivity disorder (MTA) is the first major clinical trial in its history focused on a childhood mental disorder. This article reviews the major scientific and clinical bases for initiating the MTA. METHOD: A selective review of the literature is presented in the service of describing the estimated prevalence of ADHD among children and adolescents, its core clinical features, evidence concerning psychopharmacological and psychosocial treatment effects, and related research issues and trends leading to the development of the MTA. RESULTS: Despite decades of treatment research and clinical practice, there is an insufficient basis for answering the following manifold question: under what circumstances and with what child characteristics (comorbid conditions, gender, family history, home environment, age, nutritional/metabolic status, etc.) do which treatments or combinations of treatment (stimulants, behavior therapy, parent training, school-based intervention) have what impacts (improvement, stasis, deterioration) on what domains of child functioning (cognitive, academic, behavioral, neurophysiological, neuropsychological, peer relations, family relations), for how long (short versus long term), to what extent (effect sizes, normal versus pathological range), and why (processes underlying change)? CONCLUSIONS: The important scientific, clinical, and public health issues nested within this manifold question provide both the impetus and scaffolding for the MTA.

Adolescent

Estimation of the association between desipramine and the risk for sudden death in 5- to 14-year-old children.

BACKGROUND: Four cases of sudden death in children 12 years or younger during desipramine treatment were identified between 1986 and 1992. We evaluated whether these events support the hypothesis that exposure to therapeutic doses of desipramine contributes to the risk for sudden death in otherwise healthy children. METHOD: The National Center for Health Statistics provided the baseline number of sudden unexplained deaths in children 5 to 14 years old. Data from the National Disease and Therapeutic Index were used to estimate the exposure to desipramine in children in the same age group. Since two of the four deaths were identified by 1987, we used the post-1987 experience as if it were a prospective period in which a causal association could be examined. RESULTS: The number of sudden deaths in desipramine-exposed children did not increase from 1986 to 1992 despite a marked increase in exposure. By using 4 to 6 months as the average lifetime of a desipramine prescription and a baseline rate of sudden death of 4.2 deaths/million/year in this population, the post-1987 period would account for 162,000 to 242,000 person-years of desipramine exposure. Although not statistically significant, this level of exposure corresponds to a relative risk of 2.1 (95% CI = 0.5 to 15) to 3.1 (95% CI = 0.8 to 22). CONCLUSION: Although, based on our estimates, the evidence for an association between desipramine and sudden death in children aged 5 to 14 years appears weak, replication of our findings is needed with a more precise numerator (total number of deaths) and denominator (the appropriate conversion from drug appearance to actual exposure) before a firm conclusion on this subject can be drawn. Until then, even if remote, the possibility of an association between desipramine and sudden death in children stresses the importance of assessing risks and benefits when desipramine is used in pediatric patients.

Adolescent

Pharmacotherapy of disorders of adolescents.

Despite the increase in the diversity of Axis I disorders that can appear during adolescence, the psychopharmacology treatment literature is just now focusing on their special needs and response patterns. Several findings, such as the secular increase in suicide completion among male adolescents and the lack of controlled data showing tricyclic antidepressant efficacy in this age group, underscore the unique response of adolescents to drug treatment plans that have been successful with younger and older patients. The positive response to psychostimulants for adolescents with ADHD resembles that seen in younger children. On the other hand, the great increase in suicidal behavior, particularly overdoses, that occur in patients over 12 years of age makes the choice of a nonlethal (in intentional overdose) antidepressant a critical matter. Female patients who are younger seem to achieve higher blood levels than male patients, and also show more side effects for the same weight-adjusted dose. When one adds the developmental issues of this life stage, namely the need for separation and individuation, to the complications of prescribing medications, office practice and drug management become more complicated and require a strong therapeutic alliance to ensure good compliance. These issues make the use of psychotropic medications in adolescent patients challenging and complicated, but ultimately rewarding for those clinicians who can combine psychopharmacologic knowledge with good interpersonal therapeutic skills.

Adolescent

Pharmacologic treatment of attention deficit hyperactivity disorder.

This article describes the role of psychostimulant medication in the treatment of attention deficit hyperactivity disorder. Included are the drugs' putative mechanisms of action, pharmacology, toxicology, indications for their use, short-term and long-term actions, adverse effects, specific dosing regimens, therapeutic monitoring techniques, alternative medications, and drug interactions.

Attention Deficit Disorder with Hyperactivity

Sustained release methylphenidate: pharmacokinetic studies in ADDH males.

Methylphenidate is widely used in the treatment of school-age children with attention deficit disorder with hyperactivity (ADDH). It is available in a short-acting (MPH) and a long-acting (MPH-SR) preparation. Nine males with ADDH participated in a 1-day pharmacokinetic study following a single morning dose of 20 mg. MPH-SR. Data are presented on MPH-SR's half-life (T 1/2), peak concentrations achieved (Cmax) and the time to the peak plasma concentrations (Tmax). Similar data were gathered from a second group of eight ADDH males treated with a higher, single morning dose of standard, short-acting MPH. After adjusting for dose differences, comparisons of the two sets of plasma concentration curves suggest that MPH-SR has a longer Tmax, but that it does not reach the same Cmax as an identical dose of standard MPH.

Adolescent

Childhood schizophrenia: theoretical and treatment issues.

Michael is an 8.5-year-old Caucasian male inpatient who presented at admission with severe agitation, suicidal impulses, and aggression toward his 18-month-old sister. He had been treated with stimulant medications before admission. Past history revealed bilateral genetic loading with two primary family members having a history of hallucinations and hospitalization, and two paternal aunts who were hospitalized since early childhood. Michael was raised in a chaotic, violent family environment where there was emotional, physical, and perhaps sexual abuse. Medical history included frequent staring spells. During residential treatment, more extensive interviews revealed a year's history of auditory hallucinations, inappropriate and labile affect, and a fixed delusional system. The patient was switched to neuroleptics and showed a slow response despite high doses.

Child

Molindone hydrochloride treatment of hospitalized children with conduct disorder.

Treatment-emergent symptoms and behavioral changes were assessed during an 8-week double-blind study comparing molindone and thioridazine in 31 aggressive hospitalized children (ages 6-11). Molindone was found to be as effective as thioridazine in this sample. Adverse effects differed (nonsignificantly) for the two groups, with more sedation in the thioridazine-treated children. Clinical records from 6 adolescent inpatients treated with molindone were reviewed as a comparison group. Molindone is a relatively safe neuroleptic for child and adolescent inpatients because of its short half-life and minimal prolonged tissue accumulation. Additional studies on different child populations are necessary before the proper indications for molindone usage in the pediatric group can be established.

Adolescent