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.

Influence of treatment for disruptive behavior disorders on adrenal and gonadal hormones in youth.

The study examined whether psychosocial intervention for children diagnosed with a disruptive behavior disorder (DBD; n = 84) changed concentrations of cortisol and testosterone across a 3-year follow-up when compared to a matched, nonclinical, healthy comparison (HC; n = 69) group. Boys and girls (6-11 years) with a DBD were randomly assigned to one of two arms of a multimethod intervention. Hierarchical linear modeling revealed that children undergoing psychosocial intervention for a DBD experienced a significant decline in diurnal cortisol change over time (p < .05) when compared to the HC condition. Boys with a DBD diagnosis had significantly lower mean cortisol concentrations prior to treatment (p < .05) and showed a significantly steeper increase in mean cortisol over time (p < .05) when compared to HC boys. Treatment effects for diurnal cortisol change were replicated in the boys-only analysis. No treatment effects were noted for testosterone in either analysis.

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.

Development of a Composite Primary Outcome Score for Children with Attention-Deficit/Hyperactivity Disorder and Emotional Dysregulation.

Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.

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.

The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder.

(Reprinted with permission from Am J Psychiatry 2018; 175:86-90).

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.

Attention deficit hyperactivity disorder and substance use disorders.

Attention deficit hperactivity disorder (ADHD) is highly prevalent among adolescents who have substance use disorder (SUD). Several lines of evidence, although not conclusive, suggest that ADHD might have an independent effect on SUD liability. It is still to be determined, however, whether this association is mediated by conduct disorder. This article reviews ADHD and SUD.

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.

AACAP 2005 Research Forum: speeding the adoption of evidence-based practice in pediatric psychiatry.

OBJECTIVES: At the 2005 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), the Academy's Workgroup on Research conducted a Research Forum entitled "Increasing Research Literacy Through the Adoption of Evidence-Based Practice (EBP) in Pediatric Psychiatry." METHOD: Forum participants focused on speeding the adoption of EBP across five areas: EBP as the preferred heuristic for teaching research literacy, use of EBP in training programs, dissemination of EBP in clinical practice, EBP in partnership with industry, and EBP as a framework for developing practice guidelines. RESULTS: EBP provides an easy-to-understand method for accessing and evaluating the research literature and then applying this information to decisions about patient care. Although EBP has been gaining greater visibility in pediatric psychiatry, it is far from the preferred heuristic. To move the field toward fully embracing EBP will require greater understanding of what EBP is (and is not), educating mental health professionals in EBP skills, access to EBP resources, and a commitment to apply EBP to the conceptualization and design of research protocols and practice guidelines. CONCLUSIONS: Pediatric psychiatry would benefit from a principled commitment to follow other areas of medicine in adopting EBP.

Practice parameter for the assessment and treatment of children and adolescents with depressive disorders.

This practice parameter describes the epidemiology, clinical picture, differential diagnosis, course, risk factors, and pharmacological and psychotherapy treatments of children and adolescents with major depressive or dysthymic disorders. Side effects of the antidepressants, particularly the risk of suicidal ideation and behaviors are discussed. Recommendations regarding the assessment and the acute, continuation, and maintenance treatment of these disorders are based on the existent scientific evidence as well as the current clinical practice.

Is attention-deficit/hyperactivity disorder associated with illicit substance use disorders in male adolescents? A community-based case-control study.

AIMS: This study aims at evaluating the association between attention-deficit/hyperactivity disorder (ADHD) and illicit substance use disorders (SUD) (marijuana, cocaine and inhalants), controlling for the association with conduct disorder (CD), in a community-based sample of adolescents. DESIGN: Case-control, community-based study. SETTING: A delimited geographical area in the South of Brazil, served by four public health clinics. PARTICIPANTS: A total of 968 male adolescents (15-20 years of age) were screened for SUD in their households. Of the subjects who were screened positive, we selected 61 cases with illicit SUD. For each case we selected, from the group which was screened negative, three controls without illicit or alcohol SUD, matched by age and proximity with the case's household. MEASUREMENTS: The screening instrument was the Alcohol Smoking and Substance Screening Test (ASSIST). SUD diagnoses were assessed by the drug section of the Mini International Neuropsychiatry Interview (MINI). Other psychiatric diagnoses were based on semistructured (Schedule for Affective Disorders and Schizophrenia for School-Age Children-epidemiological version; MINI) and clinical interviews. FINDINGS: Adolescents with ADHD presented a significantly higher odds ratio (OR) for illicit SUD than youths without ADHD, even after adjusting for potential confounders (CD, ethnicity, religion and estimated IQ) (OR = 9.12; 95% CI = 2.84-29.31, P < 0.01). CONCLUSIONS: Our results suggest an association between ADHD and illicit SUD in Brazilian adolescents that is not mediated by CD. These findings are potentially important from a prevention perspective because treatments are available for ADHD.

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.