Diagnostic Trends and Prescription Patterns in Disruptive Mood Dysregulation Disorder and Bipolar Disorder.

OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) was introduced in DSM-5 to distinguish a subset of chronically irritable youth who may be incorrectly diagnosed and/or treated for pediatric bipolar disorder (BPD). This study characterized the rate of new treatment episodes and treated prevalence of BPD and DMDD from a longitudinal electronic health record database and examined the impact of DMDD on prescription trends. METHOD: A retrospective cohort study using 2008-2018 Optum electronic health record data was conducted. Youth aged 10 to < 18 years with ≥ 183 days of database enrollment before the study cohort entry were included. Annual new treatment episode rates per 1,000 patient-years and treated prevalence (%) were estimated. Prescriptions for medications, concomitant diagnoses, and acute mental health service use for 2016-2018 were evaluated. RESULTS: There were 7,677 youths with DMDD and 6,480 youths with BPD identified. Mean age (13-15 years) and ethnicity were similar for both groups. A rise in new treatment episode rates (0.87-1.75 per 1,000 patient-years, p < .0001) and treated prevalence (0.08%-0.35%, p < .0001) of DMDD diagnoses (2016-2018) following diagnosis inception was paralleled by decreasing new treatment episode rates (1.22-1.14 per 1,000 patient-years, p < .01) and treated prevalence (0.42%-0.36%, p < .0001) of BPD diagnoses (2015-2018). More youth in the DMDD group were prescribed medications compared with the BPD group (81.9% vs 69.4%), including antipsychotics (58.9% vs 51.0%). Higher proportions of youth with DMDD vs youth with BPD had disruptive behavior disorders (eg, 35.9% vs 20.5% had oppositional defiant disorder), and required inpatient hospitalization related to their mental health disorder (45.0% vs 33.0%). CONCLUSION: Diagnosis of DMDD has had rapid uptake in clinical practice but is associated with increased antipsychotic and polypharmacy prescriptions and higher rates of comorbidity and inpatient hospitalization in youth with a DMDD diagnosis compared with a BPD diagnosis.

Pharmacotherapy of Aggression in Child and Adolescent Psychiatric Disorders.

OBJECTIVE: Aggression is a common, yet complex, behavioral complaint, and a frequent indication for referral to child and adolescent psychiatrist treatment. This article reviews the evidence supporting pharmacotherapy of aggression in youth, with a primary focus on impulsive aggression (the primary indication for this intervention). Relevant diagnostic considerations and consensus guidelines are discussed. METHODS: Articles examining the role of medications in the treatment of aggression in youth with pathological aggression were identified using PubMed and MEDLINE® databases over the past 15 years (2000-2015); selected articles published prior to 2000 and deemed to be of high relevance were searched and also included. Search terms included: Aggression, aggressive, disruptive behavior, conduct, youth, children, and adolescents. Cited references were also searched for relevant articles. RESULTS: There are a number of evidence-based medication treatments for aggression, which are generally best considered in the context of differential diagnosis and ongoing evidence-based psychosocial interventions. Impulsive aggression is generally considered the type of aggression most amenable to medication, but other aggression subtypes may also possibly respond to treatment. Medication classes with positive evidence include the psychostimulants and α-2 agonists (in the presence of attention-deficit/hyperactivity disorder [ADHD] and/or disruptive behavior disorders), mood stabilizing agents, and atypical antipsychotics. Published guidelines recommend systematic and adequate trials of medications in sequential order, to optimize response and minimize polypharmacy. Guidelines for safety monitoring are available for many of the medications used for aggression in youth, and are also discussed. CONCLUSIONS: Aggression in children carries a high risk of poor outcomes, and, therefore, a better understanding of treatment options is a high priority. The available literature points to the importance of identifying the underlying disorder, when possible, and using this information to guide treatment selection. Future studies are needed to better inform the treatment of aggression across disorders, and the treatment of different aggression subtypes.

Iron homeostasis during risperidone treatment in children and adolescents.

OBJECTIVE: Previous cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration. METHOD: Study 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders. RESULTS: Study 1 sample consisted of 73 participants (85% males, mean age: 7.7 ± 2.4 years). After 18.0 ± 2.0 weeks on risperidone, their BMI z score increased by 0.93 ± 0.70 points and ferritin concentration declined by 6.8 ± 13.3 µg/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (ß = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 ± 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01). CONCLUSIONS: Risperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00080145.

Antipsychotic prescription in children and adolescents: an analysis of data from a German statutory health insurance company from 2005 to 2012.

BACKGROUND: Despite sparse documentation of their long-term therapeutic effects and side effects, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in recent years, both in the USA and in Europe. No current data are available about antipsychotic prescriptions for this age group in Germany. METHODS: Data from the largest statutory health insurance fund in Germany (BARMER GEK) were studied to identify antipsychotic prescriptions for children and adolescents (age 0-19 years) from 2005 to 2012 and analyze them with respect to age, sex, drug prescribed, prescribing medical specialty, and any observable secular trends. RESULTS: The percentage of children and adolescents receiving a prescription for an antipsychotic drug rose from 0.23% in 2005 to 0.32% in 2012. In particular, atypical antipsychotic drugs were prescribed more frequently over time (from 0.10% in 2005 to 0.24% in 2012). The rise in antipsychotic prescriptions was particularly marked among 10- to 14-year-olds (from 0.24% to 0.43%) and among 15- to 19-year-olds (from 0.34% to 0.54%). The prescribing physicians were mostly either child and adolescent psychiatrists or pediatricians; the most commonly prescribed drugs were risperidone and pipamperone. Risperidone was most commonly prescribed for patients with hyperkinetic disorders and conduct disorders. CONCLUSION: In Germany as in other industrialized countries, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in ecent years. The German figures, while still lower than those from North America, are in the middle range of figures from European countries. The causes of the increase should be critically examined; if appropriate, the introduction of prescribing guidelines of a more restrictive nature could be considered.

Pharmacotherapy of attention deficit in neurofibromatosis type 1: effects on cognition.

AIM: Attention deficit with or without hyperactivity (AD[H]D) is a common comorbidity of neurofibromatosis type 1 (NF 1). We tested the hypothesis that permanent medication with methylphenidate can improve cognitive functioning in children with NF 1 and comorbid AD(H)D. PATIENTS AND METHOD: We retrospectively analyzed data of a clinical sample of patients with NF 1 with or without AD(H)D, who underwent standardized neuropsychological diagnostics twice (age range: T1, 6-14 years; T2, 7-16 years; mean interval, 49.09 months). A total of 16 children without AD(H)D (nine females) were compared with 14 unmedicated children with AD(H)D (eight females) and to 13 medicated children with AD(H)D (two females). Effects of medication and attention on cognitive outcome (IQ) were tested by repeated measures analysis of covariance (rmANCOVA). RESULTS: Medicated children with NF 1 improved significantly in full-scale IQ from T1 to T2 (IQ[T1] = 80.38, IQ[T2] = 98.38, confidence interval [diff]: -25.59 to -10.40, p < 0.0001), this effect was not evident for the other groups. With attention measures as covariates, the effect remained marginally significant. CONCLUSION: Children and adolescents with NF 1 and comorbid AD(H)D may profit from MPH medication regarding general cognition. This effect could be specific for the group of patients with NF 1, and cannot be explained solely by improvements in attention. Controlled, prospective studies are warranted to corroborate our findings.

Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. AIMS: To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD case-control study. METHOD: At baseline we assessed ADHD, conduct disorder and oppositional defiant disorder. Substance use disorders, nicotine dependence and stimulant treatment were assessed retrospectively after a mean follow-up of 4.4 years, at a mean age of 16.4 years. RESULTS: Stimulant treatment of ADHD was linked to a reduced risk for substance use disorders compared with no stimulant treatment, even after controlling for conduct disorder and oppositional defiant disorder (hazard ratio (HR) = 1.91, 95% CI 1.10-3.36), but not to nicotine dependence (HR = 1.12, 95% CI 0.45-2.96). Within the stimulant-treated group, a protective effect of age at first stimulant use on substance use disorder development was found, which diminished with age, and seemed to reverse around the age of 18. CONCLUSIONS: Stimulant treatment appears to lower the risk of developing substance use disorders and does not have an impact on the development of nicotine dependence in adolescents with ADHD.

Risk of hyperprolactinemia and sexual side effects in males 10-20 years old diagnosed with autism spectrum disorders or disruptive behavior disorder and treated with risperidone.

OBJECTIVE: The aim of this study was to investigate the long-term treatment effects of risperidone on prolactin levels and prolactin-related side effects in pubertal boys with autism spectrum disorders (ASD) and disruptive behavior disorders (DBD). METHOD: Physical healthy 10-20-year-old males with ASD (n=89) and/ or DBD (n=9) chronically treated (mean 52 months, range 16-126 months) with risperidone (group 1, n=51) or not treated with any antipsychotic (group 2, n=47) were recruited to this observational study from the child psychiatry outpatient clinic. Morning non-fasting serum prolactin levels were measured and prolactin-related side effects were assessed by means of questionnaires and physical examination. Group differences were tested with Student's t, χ(2), Fisher exact, and Mann-Whitney tests, and logistic regression analysis, according to the type and distribution of data. RESULTS: Hyperprolactinemia was present in 47% of subjects in group 1 but only in 2% of subjects in group 2 (odds ratio 71.9; 95% CI, 7.7; 676.3). Forty-six percent of subjects in group 1 had asymptomatic hyperprolactinemia. Current risperidone dose and 9-OH risperidone plasma level were significant predictors of hyperprolactinemia (p=0.035 and p=0.03, respectively). Gynecomastia and sexual dysfunction were present in 43% and 14% of the subjects in group 1, respectively, compared with 21% and 0% of subjects in group 2 (p=0.05 and p=0.01). Gynecomastia was not significantly associated with hyperprolactinemia. CONCLUSIONS: Hyperprolactinemia is a common side effect in young males treated over the long term with risperidone. Young males treated with risperidone are more likely to report diminished sexual functioning than are those not treated with antipsychotics.

Primary care prescribing psychologists in the Indian Health Service.

Some of the largest health care disparities are those related to services for American Indians and Alaska Natives (AI/ANs), who show significantly greater prevalence for diabetes, coronary heart disease, smoking, obesity, heavy alcohol use, depression, and PTSD than the general population. Given the recognition of the behavioral components of all of these conditions, the Indian Health Service, the federal agency responsible for providing comprehensive health care services to AI/ANs, has been focusing on increasing the integration of behavior health and primary care. One innovation has been to hire prescribing psychologists on primary care teams. This paper describes the role of a prescribing psychologist on three treatment teams at an IHS facility in Montana. Prescribing psychologists in the Indian Health Service can serve as valuable members of comprehensive care teams, providing exceptional wrap-around care for some of our most vulnerable and underserved citizens. This model could be an example of how a prescribing psychologist could contribute to primary care clinics in a variety of other settings.

Cerebrotendinous xanthomatosis presenting with severe externalized disorder: improvement after one year of treatment with chenodeoxycholic Acid.

Cerebrotendinous xanthomatosis (CTX) is a rare inborn disorder of sterol storage with autosomal recessive inheritance and a variable clinical presentation. We describe two siblings with an early psychiatric presentation of CTX-associated attention-deficit/hyperactivity disorder and oppositional defiant disorder, also associated with a mild intellectual disability and major behavioral impairments. In both cases, treatment with chenodeoxycholic acid improved externalized symptoms and a partial recovery of cognitive impairments was observed. This suggests that CTX is potentially reversible, demonstrating the need for early diagnosis and treatment of this disorder before irreversible neurological lesions can occur.

Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults.

There have been major advances in the treatment and understanding of attention-deficit hyperactivity disorder (ADHD) in the last decade. Among these are the availability of newer stimulant formulations, an appreciation of the combined effects of medication and behavioural therapies, and a better understanding of the neurobiology of the disorder in children (aged 6-12 years), adolescents and adults. This article focuses on the evaluation of the efficacy and safety profiles of medications used for the management of ADHD. In assessing the various medical treatments for ADHD, certain issues and analyses have become important to address. The diagnosis, characterization and quantification of ADHD symptoms are crucial to assessing treatment effectiveness. A standardized setting for measuring the severity of ADHD symptoms is the laboratory school protocol, which simulates a school environment with tightly controlled timing of measurements. This method has been adapted successfully to the adult workplace environment to help with the evaluation of adult ADHD symptoms. Statistical analyses, such as effect size and number needed to treat, may aid in the comparison and interpretation of ADHD study results. Although an objective approach to evaluating the efficacy and safety profiles of the available medications provides necessary details about the medical options, typical clinical decisions are often based on trial and error and may be individualized based on a patient's daily routine, comorbidities and risk factors. Stimulants remain the US FDA-approved medical treatment of choice for patients with ADHD and are associated with an exceptional response rate. Findings of the Multimodal Treatment of Children With ADHD study suggest that the combination of behavioural and medical therapy may benefit most patients. Nonstimulant agents, such as atomoxetine (FDA-approved), and several non-approved agents, bupropion, guanfacine and clonidine, may offer necessary alternatives to the stimulants. This is especially important for patients who have comorbidities that are contraindicated for stimulant use based on medical issues and/or risk for stimulant abuse. Typical psychiatric comorbidities in patients with ADHD include oppositional defiant disorder, conduct disorder, major depressive disorder, bipolar disorder, anxiety, substance abuse disorder, tic disorder, and Tourette's syndrome. Although relatively safe, both stimulants and atomoxetine have class-related warnings and contraindications and are associated with adverse effects that require consideration when prescribing. Polypharmacy is a common psychiatric approach to address multiple symptoms or emergent adverse effects of necessary treatments. Future research may provide an improved understanding of polypharmacy and better characterization of the factors that influence the diagnosis and successful treatment of patients with ADHD.

Lithium-induced nephrotic syndrome in a prepubertal boy.

Lithium carbonate has been recognized to induce several renal side effects, including the nephrotic syndrome. This is a report of an 11-year-old, prepubertal boy with a mood disorder treated with lithium who presented with edema, bilateral pulmonary effusions, proteinuria, and hypoalbuminemia. Renal biopsy revealed pathologic changes consistent with minimal change disease. These symptoms normalized after lithium discontinuation.

Open-label, prospective trial of olanzapine in adolescents with subaverage intelligence and disruptive behavioral disorders.

OBJECTIVE: Olanzapine, an atypical antipsychotic, has been shown to be efficacious for treatment of psychotic and mood disorders in adults. This prospective, open-label study was conducted to examine the safety and usefulness of olanzapine in treating disruptive behavior disorders in adolescents with subaverage intelligence. METHOD: Sixteen adolescents (ages 13-17 years) with borderline to moderate mental retardation and disruptive behavior were enrolled in an 8-week olanzapine trial (5-20 mg/day). Dependent measures included the Aberrant Behavior Checklist, Conners Parent Rating Scale, Clinical Global Impressions, and two side effects scales. RESULTS: Statistically significant improvement (p <.002) was found on the Irritability and Hyperactivity subscales of the Aberrant Behavior Checklist and the Conners Parent Rating Scale Hyperactivity Index. No subjects developed extrapyramidal side effects. However, four were terminated prematurely from the trial because of either worsening of symptoms (requiring psychiatric inpatient hospitalization in two subjects) or side effects. The most common side effect for the sample was weight gain (averaging 12.7 lb), with 67% of subjects gaining > or =10 lb. Although there was also a statistically significant increase in prolactin levels, no subjects reported prolactin-related side effects (e.g., gynecomastia, galactorhea, amenorrhea). CONCLUSION: Olanzapine may be useful in treating disruptive behavior in adolescents with subaverage intelligence. However, side effects, especially weight gain, are a significant issue. Future double-blind, placebo-controlled studies need to confirm these findings and assess long-term safety and outcome of olanzapine treatment.