Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents With Major and Persistent Depressive Disorders.

OBJECTIVE: To enhance the quality of care and clinical outcomes for children and adolescents with major depressive disorder (MDD) and persistent depressive disorder (PDD). The aims are as follows: (1) to summarize empirically based guidance about the psychosocial and psychopharmacologic treatment of MDD and PDD in children and adolescents; and (2) to summarize expert-based guidance about the assessment of these disorders as an integral part of treatment, and the implementation of empirically based treatments for these disorders in clinical practice. METHOD: Statements about the treatment of MDD and PDD are based upon empirical evidence derived from a critical systematic review of the scientific literature conducted by the Research Triangle Institute International-University of North Carolina at Chapel Hill (RTI-UNC) Evidence-based Practice Center under contract with the Agency for Healthcare Research and Quality (AHRQ). Evidence from meta-analyses published since the AHRQ/RTI-UNC review is also presented to support or refute the AHRQ findings. Guidance about the assessment and clinical implementation of treatments for MDD and PDD is informed by expert opinion and consensus as presented in previously published clinical practice guidelines, chapters in leading textbooks of child and adolescent psychiatry, the DSM-5-TR, and government-affiliated prescription drug information websites. RESULTS: Psychotherapy (specifically, cognitive-behavioral and interpersonal therapies) and selective serotonin reuptake inhibitor (SSRI) medication have some rigorous (randomized controlled trials, meta-analyses) empirical support as treatment options. Because effective treatment outcomes are predicated in part upon accuracy of the diagnosis, depth of the clinical formulation, and breadth of the treatment plan, comprehensive, evidence-based assessment may enhance evidence-based treatment outcomes. CONCLUSION: Disproportionate to the magnitude of the problem, there are significant limitations in the quality and quantity of rigorous empirical support for the etiology, assessment, and treatment of depression in children and adolescents. In the context of a protracted severe shortage of child and adolescent-trained behavioral health specialists, the demonstration of convenient, efficient, cost-effective, and user-friendly delivery mechanisms for safe and effective treatment of MDD and PDD is a key research need. Other research priorities include the sequencing and comparative effectiveness of depression treatments, delineation of treatment mediators and moderators, effective approaches to treatment nonresponders and disorder relapse/recurrence, long-term effects and degree of suicide risk with SSRI use, and the discovery of novel pharmacologic or interventional treatments.

Adolescent Substance Use Disorders.

Adolescent Substance Use DisordersSubstance use disorders contribute to the leading causes of death among adolescents, including homicide and suicide. Here, Simon et al. review the most recent published data on adolescent substance use disorders and the implications for clinical practice.

Measurement-Based Care in the Treatment of Adolescents with Substance Use Disorders.

Measurement-based care in adolescent substance use is an important element of the evidence-based framework of Screening, Brief Intervention, and Referral to Treatment (SBIRT). Use of a validated measure for detecting substance use, misuse, and substance use disorders is significantly more effective than the use of unvalidated tools or clinician intuition. There are now a variety of established and new validated screening tools that are available for use with adolescents and that capture the range of adolescent substance use behaviors. This area, however, continues to evolve rapidly.

Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents With Anxiety Disorders.

Anxiety disorders are among the most common psychiatric disorders in children and adolescents. As reviewed in this guideline, both cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitor (SSRI) medication have considerable empirical support as safe and effective short-term treatments for anxiety in children and adolescents. Serotonin norepinephrine reuptake inhibitor (SNRI) medication has some empirical support as an additional treatment option. In the context of a protracted severe shortage of child and adolescent-trained behavioral health specialists, research demonstrating convenient, efficient, cost-effective, and user-friendly delivery mechanisms for safe and effective treatments for child and adolescent anxiety disorders is an urgent priority. The comparative effectiveness of anxiety treatments, delineation of mediators and moderators of effective anxiety treatments, long-term effects of SSRI and SNRI use in children and adolescents, and additional evaluation of the degree of suicide risk associated with SSRIs and SNRIs remain other key research needs.

Practice Parameter for the Assessment and Treatment of Psychiatric Disorders in Children and Adolescents With Intellectual Disability (Intellectual Developmental Disorder).

Intellectual disability (intellectual developmental disorder) (ID/IDD) is both a psychiatric disorder and a risk factor for co-occurring psychiatric disorders in children and adolescents. DSM-5 introduced important changes in the conceptualization and diagnosis of ID/IDD, and current research studies clarify assessment and treatment of co-occurring psychiatric disorders in this population. Optimal assessment and treatment of psychiatric illness in children and adolescents with ID/IDD includes modifications in diagnostic and treatment techniques, appreciation of variations in the clinical presentation of psychiatric disorders, an understanding of the spectrum of etiologies of behavioral disturbance, and knowledge of psychosocial and medical interventions.

Effects of Extended-Release Methylphenidate Treatment on Cognitive Task Performance in Children with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

Objective: To examine the effectiveness of four doses of psychostimulant medication, combining extended-release methylphenidate (ER-MPH) in the morning with immediate-release MPH (IR-MPH) in the afternoon, on cognitive task performance. Method: The sample comprised 24 children (19 boys and 5 girls) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-R and the Autism Diagnostic Observation Schedule, and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age = 8.8 years, SD = 1.7; mean intelligence quotient = 85; SD = 16.8). Effects of placebo and three dose levels of ER-MPH (containing 0.21, 0.35, and 0.48 mg/kg equivalent of IR-MPH) on cognitive task performance were compared using a within-subject, crossover, placebo-controlled design. Each of the four MPH dosing regimens (placebo, low-dose MPH, medium-dose MPH, and high-dose MPH) was administered for 1 week; the dosing order was counterbalanced across children. Results: MPH treatment was associated with significant performance gains on cognitive tasks tapping sustained attention, selective attention, and impulsivity/inhibition. Dose/response was generally linear in the dose range studied, with no evidence of deterioration in performance at higher MPH doses in the dose range studied. Conclusion: The results of this study suggest that MPH formulations are associated with significant improvements on cognitive task performance in children with ASD and ADHD.

Effects of once-daily oral and transdermal methylphenidate on sleep behavior of children with ADHD.

OBJECTIVE: Methylphenidate is a leading first-line treatment for ADHD (AD/HD). This stimulant has long been suspected to adversely affect sleeping patterns of treated individuals, especially children. There are few studies on the effects of recently developed longer-acting methylphenidate treatments, such as once-daily oral or transdermal formulations, on sleep. METHOD: The authors examined eight indices of sleep behavior among children treated with either of these two methylphenidate preparations or placebo in a randomized, double-blind, multicenter, parallel-group study. RESULTS: The main predictor of sleep problems was baseline numbers or severity of preexisting sleep problems, whereas the different treatments and placebo varied little in their propensity to elicit such problems. There was no significant relationship between dosage and severity or frequency of sleep problems. CONCLUSION: The authors found little evidence that methylphenidate treatment (at least in sustained-release forms) was a significant cause of sleep problems in treated children who were carefully titrated to an optimal dose.

Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes.

OBJECTIVE: To determine the efficacy and safety of clonidine, used alone or in combination with methylphenidate, in treating attention-deficit/hyperactivity disorder (ADHD). METHOD: A 16-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 122 children, ages 7 to 12, with any subtype of ADHD, randomly assigned to clonidine, methylphenidate, clonidine in combination with methylphenidate, or placebo according to a 2 x 2 factorial design. In two successive 4-week titration periods, clonidine (or matching placebo) and added methylphenidate (or matching placebo) were adjusted to optimal doses and then continued for 8 weeks. The primary efficacy outcome was changed from baseline to week 16 on the Conners Teachers Abbreviated Symptom Questionnaire. Secondary outcomes included the Conners Abbreviated Symptom Questionnaire for Parents and the Children's Global Assessment Scale. RESULTS: On the Conners Teachers Abbreviated Symptom Questionnaire, clonidine was not found to improve ADHD symptoms, whereas subjects treated with methylphenidate showed significant improvement compared to those not treated with methylphenidate. Subjects treated with clonidine had greater improvements on the Conners Abbreviated Symptom Questionnaire for Parents and Children's Global Assessment Scale, but also a higher rate of sedation compared with subjects not treated with clonidine. CONCLUSIONS: Based on the Conners Teachers Abbreviated Symptom Questionnaire, methylphenidate offers the best combination of efficacy and tolerability for ADHD. Clonidine was well tolerated despite the frequency of sedation and did offer some benefit.

Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.

OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.

Sexual orientation and adolescent substance use: a meta-analysis and methodological review.

AIMS: Several decades of research have shown that lesbian, gay and bisexual (LGB) adults are at high risk for substance use and substance use disorders (SUDs). These problems may often start prior to young adulthood; however, relatively little is known about risk for substance use in LGB adolescents. The primary aims of this paper were to conduct a meta-analysis of the relationship between sexual orientation and adolescent substance use and a systematic review and critique of the methodological characteristics of this literature. METHODS: Medical and social science journals were searched using Medline and PsychInfo. Studies were included if they tested the relationship between sexual orientation and adolescent substance use. Eighteen published studies were identified. Data analysis procedures followed expert guidelines, and used National Institutes of Health (NIH)-sponsored meta-analysis software. RESULTS: LGB adolescents reported higher rates of substance use compared to heterosexual youth (overall odds ratio = 2.89, Cohen's d = 0.59). Effect sizes varied by gender, bisexuality status, sexual orientation definition and recruitment source. None of the studies tested mediation and only one tested moderation. One employed a matched comparison group design, one used a longitudinal design, and very few controlled for possible confounding variables. CONCLUSIONS: The odds of substance use for LGB youth were, on average, 190% higher than for heterosexual youth and substantially higher within some subpopulations of LGB youth (340% higher for bisexual youth, 400% higher for females). Causal mechanisms, protective factors and alternative explanations for this effect, as well as long-term substance use outcomes in LGB youth, remain largely unknown.

Feasibility and preliminary efficacy of an after-school program for middle schoolers with ADHD: a randomized trial in a large public middle school.

OBJECTIVE: This pilot study tests the feasibility and preliminary efficacy of an after-school treatment program for middle schoolers with ADHD using a randomized clinical trial design. METHOD: A total of 23 students with ADHD (25% female, 48% African American) from a large public middle school were randomly assigned to a 10-week program or to community comparison. Manualized treatment targeted educational, social, and recreational skills, homework completion, and school and home behavior. Parents participated. RESULTS: Recruitment and randomization targets were easily met (87% completion). Parent and teacher satisfaction was positive. Small to medium treatment effects resulted despite greater medication use in the control group, with improvements in functioning for the program-treated youth or absence of deterioration relative to the comparison group. CONCLUSION: Despite testing an abbreviated version of the after-school program (< 5 months), this study reveals feasibility and palatability for this intervention and modest beneficial effects on behavioral and academic outcomes.

Changes and challenges: managing ADHD in a fast-paced world.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of both children and adults. Undiagnosed and untreated, ADHD may have serious lifelong consequences. Research has identified diagnostic clues, neurotransmitter pathways, and psychiatric comorbidities related to ADHD, as well as effective pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have been the foundation of ADHD therapy for more than 50 years. Availability of new extended-release (XR or ER) and longer-acting (LA) formulations and novel agents allows for wider and more individualized treatment choices. Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing. Outcomes in ADHD treatment can be improved with the use of clear treatment guidelines and tools to aid clinicians in implementing them efficiently and effectively. The Texas Children's Medication Algorithm Project (CMAP) provides a system of algorithm-driven treatment decisions that is evidence based and easy to implement. OBJECTIVE: To (1) review the psychological components of attention, the neurotransmitter pathways associated with ADHD, and the array of therapeutic options for ADHD, with an emphasis on the most recent introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric and cardiovascular side effects associated with stimulants; (3) review abuse liability, comorbidities, and suggested approaches to these issues; and (4) review the development and use of CMAP and offer resources for its implementation in clinical practice. CONCLUSION: The pathophysiology of ADHD is linked to dysfunction of fronto-subcortical networks and dysregulation of dopaminergic, noradrenergic, and nicotinic neurotransmitter systems. An additive effect of multiple genes as well as environmental influences contributes to the clinical picture. Treatment with stimulants and nonstimulants has proven effective in different subgroups, with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. Availability of XR, ER, LA, and transdermal stimulant formulations, as well as alternative nonstimulant agents, offers new options for the pharmacotherapy of ADHD. Major concerns associated with abuse liability of stimulants have been allayed by the availability of ER formulations, which have reduced reinforcing effects associated with short-acting preparations. Medication outcomes in ADHD can be enhanced by the use of evidence-based algorithms such as CMAP. Keys to success are adequate initial assessment and diagnosis, the use of sustained-release products, sufficient dose titration, and the use of clinical rating scales with feedback from caregivers and teachers. Optimal treatment outcomes can be achieved by appropriate pharmacotherapy combined with psychosocial interventions.

Challenges and Gaps in Understanding Substance Use Problems in Transitional Age Youth.

Transitional age youth (TAY), developing from adolescence to adulthood, exhibit the highest level of alcohol and other drug use of any other age group. Risk factors mirror those for the development of problems and disorders in adolescents. Early screening of both college students and noncollege high-risk TAY in the community is critical to early and effective intervention. Brief interventions using motivational techniques are effective for many TAY, particularly for those in early stages of problem use on college campuses. Professionals in contact with TAY should be aware of evidence-based interventions and providers for substance use disorders in the community.

Clinical Implications From the Treatment of Severe Childhood Aggression (TOSCA) Study: A Re-Analysis and Integration of Findings.

OBJECTIVE: The Treatment of Severe Childhood Aggression (TOSCA) project examined augmentation of stimulant treatment and parent training (PT) with risperidone for severe physical aggression. This article summarizes the clinical implications; reanalyzes the data to examine the utility of 4 criteria for deciding to augment; and presents a treatment algorithm. METHOD: The newly analyzed 4 criteria for augmenting after 3 weeks of stimulant and PT treatment consisted of not meeting a Clinical Global Impressions-Improvement (CGI-I) score of 1 and a normal score (≤15) on the Nisonger Child Behavior Rating Form Disruptive-Total (D-Total); a CGI-I score of 1 or 2 plus 25% improvement in D-Total score; a D-Total score no higher than 15; and a CGI-Severity score of 3 (mild) or better. Effect sizes were calculated. Prior TOSCA publications were reviewed for clinically relevant findings. RESULTS: All 4 criteria resulted in medium or better effect sizes (d = 0.59-0.72) when comparing risperidone with placebo. Providing risperidone to children who did not reach a CGI-I score of 1 plus a D-Total score no higher than 15 resulted in the greatest benefit. In addition, a review of clinically relevant data suggests that stimulant plus PT shows further improvement after 3 weeks even without augmentation. CONCLUSION: For those children who did not attain a CGI-I score of 1 and a D-total score no higher than 15, adding risperidone maximized the number of children benefitting from treatment and the average amount of benefit. Unless clinical circumstances dictate otherwise, practitioners should delay an antipsychotic drug for at least 1 month after the optimal stimulant dose is achieved and PT has commenced. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrials.gov; NCT00796302.

Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory.

OBJECTIVE: Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory. METHODS: A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6-12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone). RESULTS: At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83). CONCLUSIONS: Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302.

The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded Treatment in Clinical Responders.

OBJECTIVES: Previous "Treatment of Severe Childhood Aggression" (TOSCA) reports demonstrated that many children with severe physical aggression and attention-deficit/hyperactivity disorder (ADHD) responded well to two randomized treatments (parent training [PT]+stimulant+placebo = Basic vs. PT+stimulant+risperidone = Augmented) for 9 weeks. An important clinical question is whether these favorable outcomes are maintained over longer times. METHODS: Clinical responders to the 9-week trial (n = 103/168), defined as Clinical Global Impressions (CGI)-Improvement of much/very much improved plus substantial reduction in parent ratings of disruptiveness, were followed another 12 weeks (21 weeks total) while remaining on blinded treatment. Outcome measures included Clinical Global Impressions scale, Nisonger Child Behavior Rating Form (NCBRF), other parent/teacher-rated scales, laboratory tests, clinician ratings of abnormal movement, and other adverse events (AEs). RESULTS: Parent ratings of problem behavior showed minimal worsening of behavior from end of the 9-week acute trial (expected from regression to the mean after selecting best responders), but outcomes at Extension endpoint were meaningfully improved compared with acute study baseline. As expected, outcomes for Basic and Augmented treatment did not differ among these children selected for good clinical response. During Extension, more Augmented subjects had elevated prolactin; there were no clinically confirmed cases of tardive dyskinesia. Delayed sleep onset was the most frequent Basic AE. We also conducted a last-observation-carried-forward analysis, which included both nonresponders and responders. We found that, at the end of Extension, Augmented subjects had more improvement than Basic subjects on the NCBRF Positive Social subscale (p = 0.005; d = 0.44), the Antisocial Behavior Scale Reactive Aggression subscale (p = 0.03; d = 0.36), and marginally so on the Disruptive Behavior Total subscale (p = 0.058; d = 0.29, the primary outcome). CONCLUSIONS: The medium-term outcomes were good for the participants in both treatment groups, perhaps because they were selected for good response. When nonresponders were included in ITT analyses, there was some indication that Augmented surpassed Basic treatment.

Regionally specific alterations in membrane phospholipids in children with ADHD: An in vivo 31P spectroscopy study.

This multi-voxel, phosphorus magnetic resonance spectroscopy ((31)P MRS) study examined the prefrontal cortex (PFC), basal ganglia (BG) and superior temporal (ST) region in 10 children with attention-deficit/hyperactivity disorder (ADHD) and 15 healthy controls. ADHD patients had lower PFC and BG phosphomonoester (PME) levels compared to healthy children. No differences were noted in the ST. These deficits in membrane phospholipid (MPL) precursor levels suggest reduced mass of cellular MPLs due to a possible underdevelopment of neuronal processes and synapses in ADHD.

Severely Aggressive Children Receiving Stimulant Medication Versus Stimulant and Risperidone: 12-Month Follow-Up of the TOSCA Trial.

OBJECTIVE: The objective of this study was to evaluate 52-week clinical outcomes of children with co-occurring attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorder, and serious physical aggression who participated in a prospective, longitudinal study that began with a controlled, 9-week clinical trial comparing the relative efficacy of parent training + stimulant medication + placebo (Basic; n = 84) versus parent training + stimulant + risperidone (Augmented; n = 84). METHOD: Almost two-thirds (n = 108; 64%) of families in the 9-week study participated in week 52 follow-ups (Basic, n = 55; Augmented, n = 53) and were representative of the initial study sample. The assessment battery included caregiver and clinician ratings and laboratory tests. RESULTS: Only 43% of participants in the Augmented group and 36% in the Basic group still adhered to their assigned regimen (not significant [NS]); 23% of those in the Augmented group and 11% in the Basic group were taking no medication (NS). Both randomized groups improved baseline to follow-up, but the 3 primary parent-reported behavioral outcomes showed no significant between-group differences. Exploratory analyses indicated that participants in the Augmented group (65%) were more likely (p = .02) to have a Clinical Global Impressions (CGI) severity score of 1 to 3 (i.e., normal to mildly ill) at follow-up than those in the Basic group (42%). Parents rated 45% of children as impaired often or very often from ADHD, noncompliant, or aggressive behavior. The Augmented group had elevated prolactin levels, and the Basic group had decreased weight over time. Findings were generally similar whether groups were defined by randomized assignment or follow-up treatment status. CONCLUSION: Both treatment strategies were associated with clinical improvement at follow-up, and primary behavioral outcomes did not differ significantly. Many children evidenced lingering mental health concerns, suggesting the need for additional research into more effective interventions. Clinical trial registration information-Treatment of Severe Childhood Aggression (the TOSCA Study); http://clinicaltrials.gov/; NCT00796302.

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.