Long-term sertraline treatment of children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: To evaluate the safety and effectiveness of sertraline in the long-term treatment of pediatric obsessive-compulsive disorder (OCD). METHOD: Children (6-12 years; n= 72) and adolescents (13-18 years; n = 65) with DSM-III-R-defined OCD who had completed a 12-week, double-blind, placebo-controlled sertraline study were given open-label sertraline 50 to 200 mg/day in this 52-week extension study. Concomitant psychotherapy was allowed during the extension study Outcome was evaluated by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), National Institute of Mental Health Global Obsessive-Compulsive Scale, and Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores. RESULTS: Significant improvement (p < .0001) was demonstrated on all four outcome parameters on an intent-to-treat analysis for the overall study population (n = 132), as well as the child and the adolescent samples. At endpoint, 72% of children and 61% of adolescents met response criteria (>25% decrease in CY-BOCS and a CGI-I score of 1 or 2). Significant (p < .05) improvements were also demonstrated from the extension study baseline to endpoint on all outcome parameters in those patients who received sertraline during the 12-week, double-blind acute study. Long-term sertraline treatment was well tolerated, and there were no discontinuations due to changes in vital signs, laboratory values, or electrocardiograms. CONCLUSION: Sertraline (50-200 mg/day) was effective and generally well tolerated in the treatment of childhood and adolescent OCD for up to 52 weeks. Improvement was seen with continued treatment.

Cognitive-behavioral family treatment of childhood obsessive-compulsive disorder: preliminary findings.

The effectiveness of a 14-week cognitive-behavioral family treatment protocol for childhood obsessive-compulsive disorder (OCD) was piloted using a volunteer sample of seven children aged 10-14 years. The primary outcome measures were diagnostic status, symptom severity, and global functioning which were assessed at pre- and post-treatment, and at three-month follow-up. A series of self-report measures assessing obsessive-compulsive symptomatology, depression, and family factors were also completed at pre- and post-treatment. The results indicated that six participants no longer met criteria for OCD at post-treatment, with a mean reduction of 60% in symptom severity. Self-reported obsessive-compulsive symptomatology and family involvement in the disorder also significantly decreased across time. The findings support the efficacy of cognitive-behavioral treatment with a structured family component for childhood OCD. Further research investigating the comparative efficacy of treatment with and without family involvement is warranted.

Advances in paediatric neuropsychopharmacology: an overview.

This Special Section of Int J Neuropsychopharmacol highlights current progress in paediatric neuropsychopharmacology. Combining critical reviews and, in some cases, new data, specific topics include: biological findings in major depression, sleep dysregulation in depressed youth, cardiovascular and ventilatory dysregulation in panic disorder, paediatric autoimmune neuropsychiatric disorder associated with strep (PANDAS), age of onset as a subtype marker in tic and obsessive--compulsive disorders (OCD), functional and pharmaconeuroanatomy of OCD and the behavioural pharmacokinetics of methylphenidate. In this introductory section, these articles are placed in the context of the state-of-the field and, more specifically, within the framework of recent NIMH initiatives in paediatric neuropsychopharmacology.

Sertraline in children and adolescents with social anxiety disorder: an open trial.

OBJECTIVE: The aim of this open-label study was to assess the therapeutic benefits, response pattern, and safety of sertraline in children with social anxiety disorder. METHOD: Fourteen outpatient subjects with a primary Axis I diagnosis of social anxiety disorder were treated in an 8-week open trial of sertraline. Diagnostic and primary outcome measures included the Anxiety Disorders Interview Schedule for Children, Clinical Global Impressions scale (CGI), Social Phobia and Anxiety Inventory for Children, and a standardized behavioral avoidance test. RESULTS: As measured by the CGI (Improvement subscale), 36% (5/14) of subjects were classified as treatment responders and 29% (4/14) as partial responders by the end of the 8-week trial. A significant clinical response appeared by week 6. Self-report and behavioral measures showed significant clinical improvement into normal range across all domains measured. The mean dose of sertraline was 123.21+/-37.29 mg per day. Sertraline was generally well tolerated. CONCLUSION: In open treatment, sertraline resulted in significant improvement in symptoms of childhood social anxiety disorder. Absolute response rates varied depending on rating scales used. Findings from this study are sufficiently strong to warrant a future multisite, randomized, double-blind, placebo-controlled trial of sertraline for treatment of childhood social anxiety disorder.

Cognitive-behavioral psychotherapy for pediatric obsessive-compulsive disorder.

Discusses the cognitive-behavioral psychotherapy for pediatric obsessive-compulsive disorder (OCD). Over the past 15 years, cognitive-behavioral psychotherapy has emerged as the psychosocial treatment of choice for OCD across lifespan. Unlike other psychotherapies that have been applied usually unsuccessfully to OCD, cognitive-behavioral treatment (CBT) presents a logically consistent and compelling relationship between the disorder, the treatment, and the specified outcome. Nevertheless, despite a consensus that CBT is usually helpful, clinicians routinely complain that patients will not comply with behavioral treatments and parents routinely complain that clinicians are poorly trained in CBT, with the result that many if not most children and adolescents are denied access to effective psychosocial treatment. This unfortunate situation may be avoidable, given an increased understanding regarding the implementation of CBT in children and adolescents with OCD. To this end, we review the principles and the practical aspects of the cognitive-behavioral treatment of OCD in youth, move on to discuss empirical studies supporting the use of CBT in the pediatric age group, and conclude by discussing directions for future research.

Findings from the NIMH Multimodal Treatment Study of ADHD (MTA): implications and applications for primary care providers.

In 1992, the National Institute of Mental Health and 6 teams of investigators began a multisite clinical trial, the Multimodal Treatment of Attention-Deficit Hyperactivity Disorder (MTA) study. Five hundred seventy-nine children were randomly assigned to either routine community care (CC) or one of three study-delivered treatments, all lasting 14 months. The three MTA treatments-monthly medication management (usually methylphenidate) following weekly titration (MedMgt), intensive behavioral treatment (Beh), and the combination (Comb)-were designed to reflect known best practices within each treatment approach. Children were assessed at four time points in multiple outcome. Results indicated that Comb and MedMgt interventions were substantially superior to Beh and CC interventions for attention-deficit hyperactivity disorder symptoms. For other functioning domains (social skills, academics, parent-child relations, oppositional behavior, anxiety/depression), results suggested slight advantages of Comb over single treatments (MedMgt, Beh) and community care. High quality medication treatment characterized by careful yet adequate dosing, three times daily methylphenidate administration, monthly follow-up visits, and communication with schools conveyed substantial benefits to those children that received it. In contrast to the overall study findings that showed the largest benefits for high quality medication management (regardless of whether given in the MedMgt or Comb group), secondary analyses revealed that Comb had a significant incremental effect over MedMgt (with a small effect size for this comparison) when categorical indicators of excellent response and when composite outcome measures were used. In addition, children with parent-defined comorbid anxiety disorders, particularly those with overlapping disruptive disorder comorbidities, showed preferential benefits to the Beh and Comb interventions. Parental attitudes and disciplinary practices appeared to mediate improved response to the Beh and Comb interventions.

ADHD comorbidity findings from the MTA study: comparing comorbid subgroups.

OBJECTIVES: Previous research has been inconclusive whether attention-deficit/hyperactivity disorder (ADHD), when comorbid with disruptive disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]), with the internalizing disorders (anxiety and/or depression), or with both, should constitute separate clinical entities. Determination of the clinical significance of potential ADHD + internalizing disorder or ADHD + ODD/CD syndromes could yield better diagnostic decision-making, treatment planning, and treatment outcomes. METHOD: Drawing upon cross-sectional and longitudinal information from 579 children (aged 7-9.9 years) with ADHD participating in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), investigators applied validational criteria to compare ADHD subjects with and without comorbid internalizing disorders and ODD/CD. RESULTS: Substantial evidence of main effects of internalizing and externalizing comorbid disorders was found. Moderate evidence of interactions of parent-reported anxiety and ODD/CD status were noted on response to treatment, indicating that children with ADHD and anxiety disorders (but no ODD/CD) were likely to respond equally well to the MTA behavioral and medication treatments. Children with ADHD-only or ADHD with ODD/CD (but without anxiety disorders) responded best to MTA medication treatments (with or without behavioral treatments), while children with multiple comorbid disorders (anxiety and ODD/CD) responded optimally to combined (medication and behavioral) treatments. CONCLUSIONS: Findings indicate that three clinical profiles, ADHD co-occurring with internalizing disorders (principally parent-reported anxiety disorders) absent any concurrent disruptive disorder (ADHD + ANX), ADHD co-occurring with ODD/CD but no anxiety (ADHD + ODD/CD), and ADHD with both anxiety and ODD/CD (ADHD + ANX + ODD/CD) may be sufficiently distinct to warrant classification as ADHD subtypes different from "pure" ADHD with neither comorbidity. Future clinical, etiological, and genetics research should explore the merits of these three ADHD classification options.

Multimodal treatment of ADHD in the MTA: an alternative outcome analysis.

OBJECTIVE: To conduct a post hoc investigation of the utility of a single composite measure of treatment outcome for the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) at 14 months postbaseline. BACKGROUND: Examination of multiple measures one at a time in the main MTA intent-to-treat outcome analyses failed to detect a statistically significant advantage of combined treatment (Comb) over medication management (MedMgt). A measure that increases power and precision using a single outcome score may be a useful alternative to multiple outcome measures. METHOD: Factor analysis of baseline scores yielded two "source factors" (parent and teacher) and one "instrument factor" (parent-child interactions). A composite score was created from the average of standardized parent and teacher measures. RESULTS: The composite was internally consistent (alpha = .83), reliable (test-retest over 3 months = 0.86), and correlated 0.61 with clinician global judgments. In an intent-to-treat analysis, Comb was statistically significantly better than all other treatments, with effect sizes ranging from small (0.28) versus MedMgt, to moderately large (0.70) versus a community comparison group. CONCLUSIONS: A composite of ADHD variables may be an important tool in future treatment trials with ADHD and may avoid some of the statistical limitations of multiple measures.

Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment.

OBJECTIVES: To develop a categorical outcome measure related to clinical decisions and to perform secondary analyses to supplement the primary analyses of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA). METHOD: End-of-treatment status was summarized by averaging the parent and teacher ratings of attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms on the Swanson, Nolan, and Pelham, version IV (SNAP-IV) scale, and low symptom-severity ("Just a Little") on this continuous measure was set as a clinical cutoff to form a categorical outcome measure reflecting successful treatment. Three orthogonal comparisons of the treatment groups (combined treatment [Comb], medication management [MedMgt], behavioral treatment [Beh], and community comparison [CC]) evaluated hypotheses about the MTA medication algorithm ("Comb + MedMgt versus Beh + CC"), multimodality superiority ("Comb versus MedMgt"), and psychosocial substitution ("Beh versus CC"). RESULTS: The summary of SNAP-IV ratings across sources and domains increased the precision of measurement by 30%. The secondary analyses of group differences in success rates (Comb = 68%; MedMgt = 56%; Beh = 34%; CC = 25%) confirmed the large effect of the MTA medication algorithm and a smaller effect of multimodality superiority, which was now statistically significant (p < .05). The psychosocial substitution effect remained negligible and nonsignificant. CONCLUSION: These secondary analyses confirm the primary findings and clarify clinical decisions about the choice between multimodal and unimodal treatment with medication.

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.

Psychosocial treatment strategies in the MTA study: rationale, methods, and critical issues in design and implementation.

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first multisite, cooperative agreement treatment study of children, and the largest psychiatric/psychological treatment trial ever conducted by the National Institute of Mental Health. It examines the effectiveness of Medication vs. Psychosocial treatment vs. their combination for treatment of ADHD and compares these experimental arms to each other and to routine community care. In a parallel group design, 579 (male and female) ADHD children, aged 7-9 years, 11 months, were randomly assigned to one of the four experimental arms, and then received 14 months of prescribed treatment (or community care) with periodic reassessments. After delineating the theoretical and empirical rationales for Psychosocial treatment of ADHD, we describe the MTA's Psychosocial Treatment strategy applied to all children in two of the four experimental arms (Psychosocial treatment alone; Combined treatment). Psychosocial treatment consisted of three major components: a Parent Training component, a two-part School Intervention component, and a child treatment component anchored in an intensive Summer Treatment Program. Components were selected based on evidence of treatment efficacy and because they address comprehensive symptom targets, settings, comorbidities, and functional domains. We delineate key conceptual and logistical issues faced by clinical researchers in design and implementation of Psychosocial research with examples of how these issues were addressed in the MTA study.

Anxiety as a predictor and outcome variable in the multimodal treatment study of children with ADHD (MTA).

Initial moderator analyses in the Multimodal Treatment Study of Children with ADHD (MTA) suggested that child anxiety ascertained by parent report on the Diagnostic Interview Schedule for Children 2.3 (DISC Anxiety) differentially moderated the outcome of treatment. Left unanswered were questions regarding the nature of DISC Anxiety, the impact of comorbid conduct problems on the moderating effect of DISC Anxiety, and the clinical significance of DISC Anxiety as a moderator of treatment outcome. Thirty-three percent of MTA subjects met DSM-III-R criteria for an anxiety disorder excluding simple phobias. Of these, two-thirds also met DSM-III-R criteria for comorbid oppositional-defiant or conduct disorder whereas one-third did not, yielding an odds ratio of approximately two for DISC Anxiety, given conduct problems. In this context, exploratory analyses of baseline data suggest that DISC Anxiety may reflect parental attributions regarding child negative affectivity and associated behavior problems (unlike fearfulness), particularly in the area of social interactions, another core component of anxiety that is more typically associated with phobic symptoms. Analyses using hierarchical linear modeling (HLM) indicate that the moderating effect of DISC Anxiety continues to favor the inclusion of psychosocial treatment for anxious ADHD children irrespective of the presence or absence of comorbid conduct problems. This effect, which is clinically meaningful, is confined primarily to parent-reported outcomes involving disruptive behavior, internalizing symptoms, and inattention; and is generally stronger for combined than unimodal treatment. Contravening earlier studies, no adverse effect of anxiety on medication response for core ADHD or other outcomes in anxious or nonanxious ADHD children was demonstrated. When treating ADHD, it is important to search for comorbid anxiety and negative affectivity and to adjust treatment strategies accordingly.

Parenting and family stress treatment outcomes in attention deficit hyperactivity disorder (ADHD): an empirical analysis in the MTA study.

Parenting and family stress treatment outcomes in the MTA study were examined. Male and female (579), 7-9-year-old children with combined type Attention Deficit Hyperactivity Disorder (ADHD), were recruited at six sites around the United States and Canada, and randomly assigned to one of four groups: intensive, multi-faceted behavior therapy program alone (Beh); carefully titrated and monitored medication management strategy alone (MedMgt); a well-integrated combination of the two (Comb); or a community comparison group (CC). Treatment occurred over 14 months, and assessments were taken at baseline, 3, 9, and 14 months. Parenting behavior and family stress were assessed using parent-report and child-report inventories. Results showed that Beh alone, MedMgt alone, and Comb produced significantly greater decreases in a parent-rated measure of negative parenting, Negative/Ineffective Discipline, than did standard community treatment. The three MTA treatments did not differ significantly from each other on this domain. No differences were noted among the four groups on positive parenting or on family stress variables. Results are discussed in terms of the theoretical and empirically documented importance of negative parenting in the symptoms, comorbidities and long-term outcomes of ADHD.

Family processes and treatment outcome in the MTA: negative/ineffective parenting practices in relation to multimodal treatment.

To elucidate processes underlying therapeutic change in a large-scale randomized clinical trial, we examined whether alterations in self-reported parenting practices were associated with the effects of behavioral, medication, or combination treatments on teacher-reported outcomes (disruptive behavior, social skills, internalizing symptoms) in children with attention-deficit hyperactivity disorder (ADHD). Participants were 579 children with Combined-type ADHD, aged 7-9.9 years, in the Multimodal Treatment Study of Children with ADHD (MTA). We uncovered 2 second-order factors of parenting practices, entitled Positive Involvement and Negative/Ineffective Discipline. Although Positive Involvement was not associated with amelioration of the school-based outcome measures, reductions in Negative/Ineffective Discipline mediated improvement in children's social skills at school. For families showing the greatest reductions in Negative/Ineffective Discipline, effects of combined medication plus behavioral treatment were pronounced in relation to regular community care. Furthermore, only in combination treatment (and not in behavioral treatment alone) was decreased Negative/Ineffective Discipline associated with reduction in children's disruptive behavior at school. Here, children in families receiving combination treatment who showed the greatest reductions in Negative/Ineffective Discipline had teacher-reported disruptive behavior that was essentially normalized. Overall, the success of combination treatment for important school-related outcomes appears related to reductions in negative and ineffective parenting practices at home; we discuss problems in interpreting the temporal sequencing of such process-outcome linkages and the means by which multimodal treatment may be mediated by psychosocial processes related to parenting.

Social phobia and separation anxiety symptoms in community and clinical samples of children and adolescents.

OBJECTIVE: To examine the developmental progression and pattern of self-reported symptoms of social phobia (SP) and separation anxiety (SA) in community (n = 2,384) and clinical (n = 217) samples of children and adolescents, using a cross-sectional method. METHOD: Subjects were cross-classified by age, gender, and race. Using mean scores on the SP and SA subscales of the Multidimensional Anxiety Scale for Children, 4 categories of children were established: HighSP/HighSA, HighSP/LowSA, LowSP/HighSA, and LowSP/LowSA. Data were analyzed using a generalized logit model. RESULTS: Community sample: Preadolescents and females reported more symptoms of HighSP/HighSA and LowSP/HighSA than adolescents and males. White children reported more symptoms of HighSP/LowSA, while the opposite pattern was found among African-American children. Clinical sample: Similar to the community sample, preadolescents reported more symptoms of HighSP/HighSA. However, clinical males reported more symptoms of LowSP/HighSA than clinical females. CONCLUSIONS: In general, adolescents endorsed more symptoms of SP and fewer symptoms of SA than preadolescent children. Irrespective of age, white children endorsed more symptoms of SP and fewer symptoms of SA than African-American children. In the community sample, preadolescent boys endorsed more symptoms of SA and fewer symptoms of SP, suggesting a possible referral bias.

Psychopharmacology of pediatric posttraumatic stress disorder.

OBJECTIVE: To review the current knowledge of pharmacotherapy in the treatment of Post-traumatic Stress Disorder (PTSD) as it applies to children and adolescents and to provide a rational approach to medication use in Pediatric PTSD. METHOD: The literature on the psychopharmacology of Pediatric PTSD is reviewed. Additionally, literature is reviewed on the neurobiological systems presumptively involved in trauma as well as studies in the pharmacology of adult PTSD, as they pertain to the treatment of Pediatric PTSD. RESULTS: There are too few studies in the current Pediatric PTSD literature to confirm treatment recommendations. Downward extrapolation from the adult literature combined with an understanding of the neurobiology of PTSD and its comorbid conditions may serve as the basis for a rational pharmacotherapy of PTSD in childhood. The effectiveness of targeting pharmacological agents at PTSD symptom clusters and associated comorbid conditions remains to be verified in controlled clinical trials. CONCLUSIONS: The state of psychopharmacology for Pediatric PTSD is in its earliest stages. While there are insufficient numbers of controlled pharmacological trials to make firm recommendations, the field requires a starting point for a rational psychopharmacological approach. Pharmacotherapy may provide symptom relief of both the debilitating primary symptoms and the comorbid conditions in children suffering from PTSD.

Test-retest reliability of the Multidimensional Anxiety Scale for Children.

We examined the test-retest reliability of the Multidimensional Anxiety Scale for Children (MASC) in a school-based sample of children and adolescents. One classroom at each grade from 3 to 12 was randomly selected to participate. Teachers were trained to administer the MASC at baseline and again 3 weeks later. The intraclass correlation coefficient (ICC) was used to estimate stability of the MASC over time. For both single case and mean ICCs, the MASC exhibited satisfactory to excellent stability across all factors and subfactors. Stability was unaffected by age or gender, but was lower for African American than Caucasian subjects. Satisfactory test-retest reliability also was demonstrated for two empirically derived subscales, the MASC-10 and Anxiety Index.

Anxiolytics, adrenergic agents, and naltrexone.

OBJECTIVE: To review extant data on the efficacy and safety of anxiolytic medications (benzodiazepines, buspirone, and other serotonin 1A agonists), adrenergic agents (beta-blockers and alpha 2-adrenergic agonists clonidine and guanfacine), and the opiate antagonist naltrexone that have been used to treat various psychopathologies in children and adolescents. To identify critical gaps in our current knowledge about these agents and needs for further research. METHOD: All available controlled trials of these medications in children and adolescents published in English through 1997 were reviewed. In addition, selected uncontrolled studies are included. RESULTS: The major finding, that there are virtually no controlled data that support the efficacy of most of these drugs for the treatment of psychiatric disorders in children and adolescents, is both surprising and unfortunate. For some drugs, e.g., buspirone and guanfacine, this is because no controlled studies have been carried out in children and/or adolescents. For other drugs, e.g., clonidine and naltrexone, most of the placebo-controlled studies have failed to demonstrate efficacy. CONCLUSIONS: The strongest recommendations for controlled studies of safety and efficacy in children and adolescents can be given for the following drugs: benzodiazepines for acute anxiety; buspirone (and newer serotonin 1A agonists as they become available) for anxiety and depression; beta-blockers for aggressive dyscontrol; guanfacine for attention-deficit/hyperactivity disorder; and naltrexone for hyperactivity, inattention, and aggression in autistic disorder.