Brieana M. Rowles

Examining the Proposed Disruptive Mood Dysregulation Disorder Diagnosis in Children in the Longitudinal Assessment of Manic Symptoms Study

OBJECTIVE To examine the proposed disruptive mood dysregulation disorder (DMDD) diagnosis in a child psychiatric outpatient population. Evaluation of DMDD included 4 domains: clinical phenomenology, delimitation from other diagnoses, longitudinal stability, and association with parental psychiatric disorders. METHOD Data were obtained from 706 children aged 6-12 years who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study (sample was accrued from November 2005 to November 2008). DSM-IV criteria were used, and assessments, which included diagnostic, symptomatic, and functional measures, were performed at intake and at 12 and 24 months of follow-up. For the current post hoc analyses, a retrospective diagnosis of DMDD was constructed using items from the K-SADS-PL-W, a version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, which resulted in criteria closely matching the proposed DSM-5 criteria for DMDD. RESULTS At intake, 26% of participants met the operational DMDD criteria. DMDD+ vs DMDD- participants had higher rates of oppositional defiant disorder (relative risk [RR] = 3.9, P < .0001) and conduct disorder (RR = 4.5, P < .0001). On multivariate analysis, DMDD+ participants had higher rates of and more severe symptoms of oppositional defiant disorder (rate and symptom severity P values < .0001) and conduct disorder (rate, P < .0001; symptom severity, P = .01), but did not differ in the rates of mood, anxiety, or attention-deficit/hyperactivity disorders or in severity of inattentive, hyperactive, manic, depressive, or anxiety symptoms. Most of the participants with oppositional defiant disorder (58%) or conduct disorder (61%) met DMDD criteria, but those who were DMDD+ vs DMDD- did not differ in diagnostic comorbidity, symptom severity, or functional impairment. Over 2-year follow-up, 40% of the LAMS sample met DMDD criteria at least once, but 52% of these participants met criteria at only 1 assessment. DMDD was not associated with new onset of mood or anxiety disorders or with parental psychiatric history. CONCLUSIONS In this clinical sample, DMDD could not be delimited from oppositional defiant disorder and conduct disorder, had limited diagnostic stability, and was not associated with current, future-onset, or parental history of mood or anxiety disorders. These findings raise concerns about the diagnostic utility of DMDD in clinical populations.

Characteristics of children with elevated symptoms of mania: The Longitudinal Assessment of Manic Symptoms (LAMS) study

OBJECTIVE The aim of the Longitudinal Assessment of Manic Symptoms (LAMS) study is to examine differences in psychiatric symptomatology, diagnoses, demographics, functioning, and psychotropic medication exposure in children with elevated symptoms of mania (ESM) compared to youth without ESM. This article describes the initial demographic information, diagnostic and symptom prevalence, and medication exposure for the LAMS cohort that will be followed longitudinally. METHOD Guardians of consecutively ascertained new outpatients 6 to 12 years of age presenting for treatment at one of 10 university-affiliated mental health centers were asked to complete the Parent General Behavior Inventory-10-Item Mania Scale (PGBI-10M). Patients with scores ≥ 12 on the PGBI-10M (ESM+) and a matched sample of patients who screened negative (ESM-) were invited to participate. Patients were enrolled from December 13, 2005, to December 18, 2008. RESULTS 707 children (621 ESM+, 86 ESM-; mean [SD] age = 9.4 [2.0] years) were evaluated. The ESM+ group, compared to the ESM- group, more frequently met DSM-IV criteria for a mood disorder (P < .001), bipolar spectrum disorders (BPSD; P < .001), and disruptive behavior disorders (P < .01). Furthermore, they showed poorer overall functioning and more severe manic, depressive, attention-deficit/hyperactivity, disruptive behavioral, and anxiety symptoms. Nevertheless, rates of BPSD were relatively low in the ESM+ group (25%), with almost half of these BPSD patients (12.1% of ESM+ patients) meeting DSM-IV criteria for bipolar disorder not otherwise specified. ESM+ children with BPSD had significantly more of the following: current prescriptions for antipsychotics, mood stabilizers, and anticonvulsants (P < .001 for each); psychiatric hospitalizations (P < .001); and biological parents with elevated mood (P = .001 for mothers, P < .013 for fathers). ESM+ children with BPSD were also lower functioning compared to ESM+ children without BPSD. CONCLUSIONS Although ESM+ was associated with higher rates of BPSD than ESM-, 75% of ESM+ children did not meet criteria for BPSD. Results suggest that longitudinal assessment is needed to examine which factors are associated with diagnostic evolution to BPSD in children with elevated symptoms of mania.

Pharmacological Treatment Options for Autism Spectrum Disorders in Children and Adolescents

&NA; Autism and other pervasive developmental disorders (PDDs) are frequently associated with dysfunctional behaviors and are characterized by deficits in socialization, communication, and behavioral rigidity. Despite the absence of a pharmacological cure for PDDs, many of the dysfunctional, coinciding behaviors may be treated pharmacologically. This article reviews what is known about the efficacy and tolerability of pharmacological interventions for the treatment of children and adolescents suffering from autistic spectrum disorders.

Double-blind, randomized, placebo-controlled long-term maintenance study of aripiprazole in children with bipolar disorder

BACKGROUND This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders. METHOD Outpatients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder (I, II, not otherwise specified, cyclothymia) were eligible to receive up to 16 weeks of open-label treatment with aripiprazole (phase 1). Patients were randomized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization (phase 2). During phase 2, patients either remained on their current aripiprazole regimen or began a double-blind taper with aripiprazole discontinued and switched to placebo. The primary outcome measure for phase 2 was time to discontinuation due to a mood event. RESULTS Patients were recruited between May 2004 and November 2008. Following phase 1, in which 96 patients received aripiprazole, 30 patients (mean age = 7.1 years) were randomly assigned to continue aripiprazole and 30 patients (mean age = 6.7 years) were randomly assigned to placebo. The mean (SD) dose of aripiprazole prior to randomization for these patients was 6.4 (2.1) mg/d. Patients randomly assigned to aripiprazole were enrolled significantly longer until time to study discontinuation due to a mood event (6.14 median weeks, SE ± 11.88 weeks; P = .005) and discontinuation for any reason (including mood events) (4.00 median weeks, SE ± 3.91 weeks; P = .003) than those randomly assigned to placebo (mood event, 2.29 median weeks, SE ± 0.38 weeks; any reason, 2.00 median weeks, SE ± 0.31 weeks). Regardless of random assignment, both the aripiprazole and placebo groups showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks (15/30 [50%] for aripiprazole; 27/30 [90%] for placebo), suggesting a possible nocebo effect (ie, knowledge of possibly switching from active medication to placebo increasing concern about relapse). The most frequently reported adverse events during double-blind aripiprazole therapy included stomach pain (n = 10, 33%), increased appetite (n = 9, 30%), and headaches (n = 9, 30%). CONCLUSIONS Despite the possibility of a nocebo effect, these results suggest that aripiprazole may be superior to placebo in the long-term treatment of pediatric patients following stabilization with open-label aripiprazole. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00194077.

The 24-month course of manic symptoms in children.

The Longitudinal Assessment of Manic Symptoms (LAMS) study was designed to investigate phenomenology and establish predictors of functional outcomes in children with elevated manic symptoms. The purpose of this series of analyses was to determine whether the participants demonstrated different trajectories of parent‐reported manic and biphasic symptoms over the first 24 months of follow‐up and to describe the clinical characteristics of the trajectories.

Review of Pharmacotherapy Options for the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and ADHD-Like Symptoms in Children and Adolescents with Developmental Disorders.

Developmental disorders such as subaverage intelligence, pervasive developmental disorders, and genetic syndromes are frequently associated with comorbid attention-deficit/hyperactivity disorder (ADHD) or ADHD-like symptoms. While there are not pharmacological cures for these developmental disorders, coinciding ADHD and ADHD-like symptoms that contribute to difficulties in psychosocial functioning are frequently able to be addressed by pharmacotherapy. This article reviews what is known about the efficacy and tolerability of pharmacological interventions for the treatment of children and adolescents suffering from developmental disorders and comorbid ADHD/ADHD-like symptoms.

Post-acute effectiveness of lithium in pediatric bipolar i disorder

OBJECTIVE This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions. METHODS Outpatients, ages 7-17 years, meeting American Psychiatric Association, diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV) diagnostic criteria for bipolar disorder I (BP-I) (manic or mixed) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium (phase I) were eligible to receive open-label lithium for an additional 16 weeks (phase II). Up to two adjunctive medications could be prescribed to patients experiencing residual symptoms of mania or comorbid psychiatric conditions, following a standardized algorithm. RESULTS Forty-one patients received continued open-label long-term treatment with lithium for a mean of 14.9 (3.0) weeks during phase II. The mean weight-adjusted total daily dose at end of phase II was 27.8 (6.7) mg/kg/day, with an average lithium concentration of 1.0 (0.3) mEq/L. Twenty-five of the 41 patients (60.9%) were prescribed adjunctive psychotropic medications for residual symptoms. The most frequent indications for adjunctive medications were refractory mania (n=13; 31.7%) and attention-deficit/hyperactivity disorder (ADHD) (n=15; 36.6%). At the end of this phase 28 (68.3%) patients met a priori criteria for response (≥50% reduction from phase I baseline in young mania rating scale [YMRS] summary score and a clinical global impressions-improvement [CGI-I] score of 1 or 2), with 22 (53.7%) considered to be in remission (YMRS summary score≤12 and CGI-severity score of 1 or 2). These data suggest that patients who initially responded to lithium maintained mood stabilization during continuation treatment, but partial responders did not experience further improvement during Phase II, despite the opportunity to receive adjunctive medications. The most commonly reported (≥20%) adverse events associated with lithium treatment were vomiting, headache, abdominal pain, and tremor. CONCLUSIONS Lithium may be a safe and effective longer-term treatment for patients with pediatric bipolar disorder who respond to acute treatment with lithium. Partial responders to acute lithium did not appear to experience substantial symptom improvement during the continuation phase, despite the possibility that adjunctive medications could be prescribed.

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

BACKGROUND: Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking. METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7–17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. RESULTS: The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression–Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (–0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain. CONCLUSIONS: Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.

Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder

OBJECTIVE The primary goal of this exploratory study was to obtain data that could lead to evidence-based dosing strategies for lithium in children and adolescents suffering from bipolar I disorder. METHODS Outpatients aged 7-17 years meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic criteria for bipolar I disorder (manic or mixed) were eligible for 8 weeks of open label treatment with lithium in one of three dosing arms. In Arm I, participants began treatment at a dose of 300 mg of lithium twice daily. The starting dose of lithium in Arms II and III was 300 mg thrice daily. Patients in Arms I and II could have their dose increased by 300 mg/day, depending on clinical response, at weekly visits. Patients in Arm III also had mid-week telephone interviews after which they could also have their dose of lithium increased by 300 mg per day. Youths weighing <30 kg were automatically assigned to Arm I, whereas youths weighing ≥30 kg were randomly assigned to Arm I, II, or III. Randomization was balanced by age (7-11 years, 12-17 years) and sex in approximately equal numbers. A priori response criteria were defined as a Clinical Global Impressions-Improvement scale score of ≤ 2 and a 50% decrease from baseline on the Young Mania Rating Scale. RESULTS Of the 61 youths [32 males (52.5%)] who received open-label lithium, 60 youths completed at least 1 week of treatment and returned for a postbaseline assessment. Most patients had a ≥ 50% improvement in Young Mania Rating Scale score, and more than half of the patients (58%) achieved response. Overall, lithium was well tolerated. All three treatment arms had similar effectiveness, side effect profiles, and tolerability of lithium. CONCLUSIONS On the basis of these results, a dosing strategy in which pediatric patients begin lithium at a dose of 300 mg thrice daily (with an additional 300 mg increase during the first week), followed by 300 mg weekly increases until a priori stopping criteria are met, will be used in an upcoming randomized, placebo-controlled trial.

Phenomenology of bipolar disorder not otherwise specified in youth: a comparison of clinical characteristics across the spectrum of manic symptoms.

Controversy surrounds the diagnostic categorization of children with episodic moods that cause impairment, but do not meet DSM‐IV criteria for bipolar I (BD‐I) or bipolar II (BD‐II) disorder. This study aimed to characterize the degree to which these children, who meet criteria for bipolar disorder not otherwise specified (BD‐NOS), are similar to those with full syndromal BD, versus those with no bipolar spectrum diagnosis (no BSD).