Bipolar disorder is frequently clinically diagnosed in youths who do not actually satisfy DSM-IV criteria, yet cases that would satisfy full DSM-IV criteria are often undetected clinically. Evidence-based assessment methods that incorporate Bayesian reasoning have demonstrated improved diagnostic accuracy, and consistency; however, their clinical utility is largely unexplored. The present study examines the effectiveness of promising evidence-based decision-making compared to the clinical gold standard. Participants were 562 youth, ages 5-17 and predominantly African American, drawn from a community mental health clinic. Research diagnoses combined semi-structured interview with youths’ psychiatric, developmental, and family mental health histories. Independent Bayesian estimates relied on published risk estimates from other samples discriminated bipolar diagnoses, Area Under Curve=.75, p<.00005. The Bayes and confidence ratings correlated rs =.30. Agreement about an evidence-based assessment intervention “threshold model” (wait/assess/treat) had K=.24, p<.05. No potential moderators of agreement between the Bayesian estimates and confidence ratings, including type of bipolar illness, were significant. Bayesian risk estimates were highly correlated with logistic regression estimates using optimal sample weights, r=.81, p<.0005. Clinical and Bayesian approaches agree in terms of overall concordance and deciding next clinical action, even when Bayesian predictions are based on published estimates from clinically and demographically different samples. Evidence-based assessment methods may be useful in settings that cannot routinely employ gold standard assessments, and they may help decrease rates of overdiagnosis while promoting earlier identification of true cases.
pediatric bipolar disorder; evidence-based assessment; decision-making; diagnosis; clinical judgment
Goals of the paper were to use item response theory (IRT) to assess the relation of depressive symptoms to the underlying dimension of depression and to demonstrate how IRT-based measurement strategies can yield more reliable data about depression severity than conventional symptom counts. Participants were 3403 clinic and nonclinic children and adolescents from 12 contributing samples, all of whom received the Kiddie Schedule of Affective Disorders and Schizophrenia for school-aged children. Results revealed that some symptoms reflected higher levels of depression and were more discriminating than others. Results further demonstrated that utilization of IRT-based information about symptom severity and discriminability in the measurement of depression severity can reduce measurement error and increase measurement fidelity.
Item Response Theory (IRT); Depression; Children; Adolescents; Kiddie-SADS (K-SADS); Psychopathology; Symptoms
To determine the contribution of parent-reported manic symptoms, family history, stressful life events, and family environment in predicting diagnosis of bipolar spectrum disorders (BPSD) in youth presenting to an outpatient psychiatric clinic.
A total of 707 6- to 12-year-old children [621 with elevated symptoms of mania (ESM+) based on screening via the Parent General Behavior Inventory 10-item Mania Scale (PGBI-10M) and 86 without ESM (ESM−)] received a comprehensive assessment.
Of the 629 with complete data, 24% (n = 148) had BPSD. Compared to those without BPSD (n = 481), children with BPSD: were older (Cohen’s d = 0.44) and more likely to be female (Cohen’s d = 0.26); had higher parent-endorsed manic symptom scores at screening (Cohen’s d = 0.36) and baseline (Cohen’s d = 0.76), more biological parents with a history of manic symptoms (Cohen’s d = 0.48), and greater parenting stress (Cohen’s d = 0.19). Discriminating variables, in order, were: baseline PGBI-10M scores, biological parent history of mania, parenting stress, and screening PGBI-10M scores. Absence of all these factors reduced risk of BPSD from 24% to 2%.
History of parental manic symptoms remains a robust predictor of BPSD in youth seeking outpatient care, even after accounting for parent report of manic symptoms in the child at screening. However, the risk factors identified as associated with BPSD, together had limited value in accurately identifying individual participants with BPSD, highlighting the need for careful clinical assessment.
bipolar disorder; children; family history; risk factors; high-risk; family environment; stressful life events
Robust screening measures that perform well in different populations could help improve the accuracy of diagnosis of pediatric bipolar disorder. Changes in sampling could influence the performance of items and potentially influence total scores enough to alter the predictive utility of scores. Additionally, creating a brief version of a measure by extracting items from a longer scale might cause differential functioning due to context effects. The current study examines both sampling and context effects of a brief measure of pediatric mania. Caregivers of 813 youths completed the parent-report General Behavior Inventory (PGBI) at an academic medical center enriched for mood disorders. Caregivers of 481 youth completed the PGBI at a community mental health center. Caregivers of 799 youth completed 10 items extracted from the PGBI at a community setting. Caregivers of 159 youth completed both versions of the PGBI and a semi-structured diagnostic interview. Differential item functioning indicated that across samples some items functioned differently; however, total observed scores were similar across all levels of mania. Receiver Operating Characteristic analysis indicated that the ten extracted items discriminated bipolar from non-bipolar as well as when the items were embedded within the full measure. Findings suggest that the extracted items perform similarly to the embedded items in the community setting. Measurement properties appear sufficiently robust across settings to support clinical applications.
Bipolar Disorder; Sensitivity; Specificity; Differential Item Functioning
To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS).
Neurocognitive functioning of youth (ages 8–19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site randomized, double-blind clinical trial comparing molindone, olanzapine or risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses.
Seventy-seven of 116 TEOSS participants (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores.
Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS.
early-onset; schizophrenia; neurocognition; outcomes; antipsychotics
This article explores aspects of family environment and parent–child conflict that may predict or moderate response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive behavioral therapy, their combination, or placebo. Outcomes were Week 12 scores on measures of depression and global impairment. Of 20 candidate variables, one predictor emerged: Across treatments, adolescents with mothers who reported less parent–child conflict were more likely to benefit than their counterparts. When family functioning moderated outcome, adolescents who endorsed more negative environments were more likely to benefit from fluoxetine. Similarly, when moderating effects were seen on cognitive behavioral therapy conditions, they were in the direction of being less effective among teens reporting poorer family environments.
To find, review, and critically evaluate evidence pertaining to the phenomenology of pediatric bipolar disorder and its validity as a diagnosis.
The present qualitative review summarizes and synthesizes available evidence about the phenomenology of bipolar disorder (BD) in youths, including description of the diagnostic sensitivity and specificity of symptoms, clarification about rates of cycling and mixed states, and discussion about chronic versus episodic presentations of mood dysregulation. The validity of the diagnosis of BD in youths is also evaluated based on traditional criteria including associated demographic characteristics, family environmental features, genetic bases, longitudinal studies of youths at risk of developing BD as well as youths already manifesting symptoms on the bipolar spectrum, treatment studies and pharmacologic dissection, neurobiological findings (including morphological and functional data), and other related laboratory findings. Additional sections review impairment and quality of life, personality and temperamental correlates, the clinical utility of a bipolar diagnosis in youths, and the dimensional versus categorical distinction as it applies to mood disorder in youths.
A schema for diagnosis of BD in youths is developed, including a review of different operational definitions of `bipolar not otherwise specified.' Principal areas of disagreement appear to include the relative role of elated versus irritable mood in assessment, and also the limits of the extent of the bipolar spectrum – when do definitions become so broad that they are no longer describing `bipolar' cases?
In spite of these areas of disagreement, considerable evidence has amassed supporting the validity of the bipolar diagnosis in children and adolescents.
bipolar disorder; children and adolescents; diagnosis; phenomenology; sensitivity and specificity
To assess whether combination treatment with lithium and divalproex is more effective than lithium monotherapy in prolonging the time to mood episode recurrence in patients with rapid-cycling bipolar disorder (RCBD) and comorbid substance abuse and/or dependence.
A 6-month, double-blind, parallel group comparison was carried out in recently manic/hypomanic/mixed patients who had demonstrated a persistent bimodal response to combined treatment with lithium and divalproex. Subjects were randomly assigned to remain on combination treatment or to discontinue divalproex and remain on lithium monotherapy.
Of 149 patients enrolled into the open-label acute stabilization phase, 79% discontinued prematurely (poor adherence: 42%; nonresponse: 25%; intolerable side effects: 10%). Of 31 patients (21%) randomly assigned to double-blind maintenance treatment, 55% relapsed (24% into depression and 76% into a manic/hypomanic/mixed episode), 26% completed the study, and 19% were poorly adherent or exited prematurely. The median time to recurrence of a new mood episode was 15.9 weeks for patients receiving lithium monotherapy and 17.8 weeks for patients receiving the combination of lithium and divalproex (p=NS). The rate of relapse into a mood episode for those receiving lithium monotherapy or the combination of lithium and divalproex was 56% and 53%, respectively. The rate of depressive relapse in both arms was 13%, while the rate of relapse into a manic, hypomanic, or mixed episode was 44% for lithium monotherapy and 40% for the combination of lithium and divalproex.
A small subgroup of patients in this study stabilized after six months of treatment with lithium plus divalproex. Of those who did, the addition of divalproex to lithium conferred no additional prophylactic benefit over lithium alone. Although depression is regarded as the hallmark of RCBD in general, these data suggest that recurrent episodes of mania tend to be more common in presentations accompanied by comorbid substance use.
Bipolar disorder; Rapid cycling; Dual-diagnosis; Substance use disorder; Maintenance trial; Placebo-controlled trial; Lithium; Divalproex; Combination pharmacotherapy
“With Significant Callous-Unemotional Traits” has been proposed as a specifier for Conduct Disorder (CD) in the upcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The impact of this specifier on children diagnosed with CD should be considered.
A multi-site cross-sectional design with volunteers (n=1136) in the 3rd-7th grades and 566 consecutive referrals (ages 5-18) to a community mental health center were used to estimate the prevalence rates of CD with and without the proposed specifier. In addition, the degree of emotional and behavioral (especially physical aggression) disturbance and level of impairment in youth with and without CD and with and without the specifier was evaluated.
In the community sample, 10% to 32% of those with CD and 2% to 7% of those without CD met the callous-unemotional (CU) specifier threshold depending on informant. In the clinic-referred sample, 21% to 50% of those with CD and 14% to 32% without CD met the CU specifier threshold depending on informant. Those with CD and the specifier showed higher rates of aggression in both samples and higher rates of cruelty in the clinic-referred sample.
Results indicate between 10% and 50% of youth with CD would be designated with the proposed CU specifier. Those with CD and the specifier appear to be more severe on a number of indices, including aggression and cruelty.
Callous-Unemotional Traits; Conduct Disorder; DSM-5; Aggression; Youth
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.
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.
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.
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.
This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder.
In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference >35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months.
Pioglitazone decreased depression symptom severity from a total IDS score of 40.3 ± 1.8 to 19.2 ± 1.8 at week 12 (p<.001). Among partial responders (≥ 25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration = 24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (−0.8 ± 0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (−0.87 ± 0.72; p<.001). During the current episode, the majority of participants (74%, n=17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects.
These data are limited by a small sample size and an open-label study design with no placebo control.
Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.
During childhood and adolescence, physiological, psychological, and behavioral processes strongly promote weight gain and increased appetite while also inhibiting weight loss and decreased appetite. The Diagnostic and Statistical Manual-IV (DSM–IV) treats both weight-gain/increased-appetite and weight-loss/decreased-appetite as symptoms of major depression during these developmental periods, despite the fact that one complements typical development and the other opposes it. To disentangle the developmental versus pathological correlates of weight and appetite disturbance in younger age groups, the current study examined symptoms of depression in an aggregated sample of 2307 children and adolescents, 47.25% of whom met criteria for major depressive disorder. A multigroup, multidimensional item response theory model generated three key results. First, weight loss and decreased appetite loaded strongly onto a general depression dimension; in contrast, weight gain and increased appetite did not. Instead, weight gain and increased appetite loaded onto a separate dimension that did not correlate strongly with general depression. Second, inclusion or exclusion of weight gain and increased appetite affected neither the nature of the general depression dimension nor the fidelity of major depressive disorder diagnosis. Third, the general depression dimension and the weight-gain/ increased-appetite dimension showed different patterns across age and gender. In child and adolescent populations, these results call into question the utility of weight gain and increased appetite as indicators of depression. This has serious implications for the diagnostic criteria of depression in children and adolescents. These findings inform a revision of the DSM, with implications for the diagnosis of depression in this age group and for research on depression.
depression; K-SADS; IRT; weight; appetite
The primary aim of the present study was to evaluate the validity of proposed DSM-5 criteria for Autism Spectrum Disorder (ASD).
We analyzed symptoms from 14,744 siblings (8,911 ASD; 5,863 non-ASD) included in a national registry, the Interactive Autism Network. Youth aged 2–18 were included if at least one child in the family was diagnosed with ASD. Caregivers reported symptoms using the Social Responsiveness Scale and the Social Communication Questionnaire. The structure of autism symptoms was examined using latent variable models that included categories, dimensions, or hybrid models specifying categories and sub-dimensions. Diagnostic efficiency statistics evaluated the proposed DSM-5 algorithm in identifying ASD.
A hybrid model that included both a category (ASD vs. non-ASD) and two symptom dimensions (social communication/interaction and restricted/repetitive behaviors) was more parsimonious than all other models and replicated across measures and sub-samples. Empirical classifications from this hybrid model closely mirrored clinical ASD diagnoses (90% overlap), implying a broad ASD category distinct from non-ASD. DSM-5 criteria had superior specificity relative to DSM-IV-TR criteria (.97 vs. .86), however sensitivity was lower (.81 vs. .95). Relaxing DSM-5 criteria by requiring one less symptom criterion increased sensitivity (.93 vs. .81), with minimal reduction in specificity (.95 vs. .97).
Results supported the validity of proposed DSM-5 criteria for ASD as provided in Phase I field trials criteria. Increased specificity of DSM-5 relative to DSM-IV-TR may reduce false positive diagnoses, a particularly relevant consideration for low base rate clinical settings. Phase II testing of DSM-5 should consider a relaxed algorithm, without which as many as 12% of ASD-affected individuals, particularly females, will be missed. Relaxed DSM-5 criteria may improve identification of ASD, decreasing societal costs through appropriate early diagnosis and maximizing intervention resources.
Autism Spectrum Disorder; diagnosis; factor analysis; latent class; factor mixture
Psychiatric treatment for children and adolescents with clinically significant aggression is common and often involves the use of antipsychotic medications. Increasingly, pediatricians are initiating or managing such treatments despite limited evidence on optimal diagnostic, psychosocial, and medication approaches for pediatric aggression.
The objective of this study was to gather clinicians' and researchers' expertise concerning the treatment of maladaptive aggression, using expert consensus survey methods to aid the development of guidelines for pediatricians and psychiatrists on the outpatient treatment of maladaptive aggression in youth (T-MAY).
Forty-six experts (psychiatrists, pediatricians, and researchers) with >10 years of clinical and/or research experience in the treatment of pediatric aggression completed a 27-item survey (>400 treatment alternatives) about optimal diagnostic, psychosocial, and medication treatments. Data were analyzed using descriptive statistics and confidence intervals.
Expert consensus methodology clearly differentiated optimal versus nonoptimal treatment strategies for maladaptive aggression. In contrast to current practice trends, results indicated that experts support the use of psychosocial interventions and parent education and training before the use of medication for maladaptive aggression at every stage of medication treatment, from diagnosis to maintenance to medication discontinuation.
Overall findings indicate that evidence-informed strategies for outpatient treatment of pediatric maladaptive aggression, guided by systematically derived expert opinions, are attainable. In light of the gap between the research literature and clinical practice, expert consensus opinion supports specific practices for optimal outpatient management in children and adolescents with severe and persistent behavioral difficulties.
A rapid-cycling course in bipolar disorder has previously been identified as a risk factor for attempted suicide. This study investigated factors associated with suicide attempts in patients with rapid-cycling bipolar I or II disorder.
Cross-sectional data at the initial assessment of patients who were enrolled into 4 clinical trials were used to study the factors associated with suicide attempt. An extensive clinical interview and the Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV diagnoses of rapid-cycling bipolar disorder, substance use disorders, anxiety disorders, psychosis, and other clinical variables. Chi-square, t test, and logistic regression or Poisson regression were used to analyze the data where appropriate, with odds ratios (ORs) for relative risk estimate. The data were collected from September 1995 to June 2005.
In a univariate analysis, 41% of 561 patients had at least 1 lifetime suicide attempt. Earlier age of depression onset, bipolar I subtype, female sex, unmarried status, and a history of drug use disorder, panic disorder, sexual abuse, and psychosis were associated with significantly higher rates of attempted suicide (all p<.05). After considering 31 potential confounding factors in the stepwise logistic regression model (n = 387), any Axis I comorbidity (OR=2.68, p = .0219), female sex (OR= 2.11, p = .0005), psychosis during depression (OR = 1.84, p = .0167), bipolar I subtype (OR= 1.83, p = .0074), and history of drug abuse (OR = 1.62, p = .0317) were independent predictors for increased risk of attempted suicide. However, white race was associated with a lower risk for suicide attempt (OR = 0.47, p = .0160). Psychosis during depression (p = .0003), bipolar I subtype (p = .0302), and physical abuse (p = .0195) were associated with increased numbers of suicide attempts by 248%, 166%, and 162%, respectively; white race was associated with a 60% decrease in the number of suicide attempts (p=.0320).
In this highly comorbid group of patients with rapid-cycling bipolar disorder, 41% had at least 1 suicide attempt. Among the demographics, female sex was positively associated, but white race was negatively associated, with the risk for suicide attempt. Independent clinical variables for increased risk and/or number of attempted suicides were any Axis I comorbidity, psychosis during depression, bipolar I subtype, a history of drug abuse, and physical abuse.
To pilot the efficacy and safety data of lamotrigine adjunctive therapy to lithium and divalproex in patients with rapid-cycling bipolar disorder (RCBD) and a recent substance use disorder (SUD).
Structured Clinical interviews were used to ascertain DSM-IV diagnosis of RCBD, SUDs, and other Axis I disorders. Patients who did not meet the criteria for a bimodal response after up to 16-weeks of open-label treatment with lithium plus divalproex, as measured by MADRS (Montgomery-Asberg Depression Rating Scale) ≤ 19, YMRS (Young Mania Rating Scale) ≤ 12 and GAF (Global Assessment of Functioning) ≥ 51 for 4 weeks, were rendomized to a 12-week, double-blind addition of lamotrigine or placebo to lithium plus divalproex. Primary and secondary outcomes were analyzed with ANCOVA, t-test, of chi-square/Fisher's exact.
Of 98 patients enrolled into the study, 36 were randomized to receive lamotrigine (n = 18) or placebo (n = 18), and 8 patients per arm completed the study. No patient discontinued due to adverse events. The change in MADRS total score from baseline to endpoint was –9.1 ± 11.2 in lamotrigine-treated patients versus –4.5 ± 13.1 in placebo-treated patients (p = 0.27). Therre were no significant differences in changes in YMRS total scores and rates of response or remission.
Lamotrigine adjunctive therapy was well toletated in patients previously non-responsive to initial treatment of lithium plus divalproex. A larger study is warranted to determine the efficacy and safety of adjunctive lamotrigine versus placebo in RCBD with a recent SUD.
Bipolar disorder; substance use disorder; mood stabilizer; lamotrigine; placebo-controlled trial; treament-refractory
This study explored the demographic and diagnostic features of children who were currently receiving antipsychotics compared to children who were receiving other psychotropics in a cohort of children with and without elevated symptoms of mania (ESM). Participants were recruited from 10 child outpatient mental health clinics associated with four universities. Guardians with children between 6–12 years who presented for new clinical evaluations completed the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M). All children who scored ≥12 on the PGBI-10M and a select demographically matched comparison group of patients who scored ≤11 were invited to participate. Children were divided into two groups: those receiving at least one antipsychotic medication and those receiving other psychotropic medications. The groups were compared on demographics, diagnoses, psychiatric symptoms, functioning, and past hospitalizations. Of the 707 children enrolled in the Longitudinal Assessment of Manic Symptoms (LAMS) study, 443 (63%) were prescribed psychotropic medication at baseline: 157 (35%) were receiving an antipsychotic and 286 (65%) were prescribed other agents. Multivariate results indicated that being prescribed antipsychotics was related to being white, previous hospitalization, having a psychotic or bipolar 1 disorder and the site where the child was receiving services (p<0.001). In this sample, it is relatively common for a child to be prescribed an antipsychotic medication. However, the only diagnoses associated with a greater likelihood of being treated with an antipsychotic were psychotic disorders or unmodified DSM-IV bipolar 1 disorder.
The purpose of this open-label study was to describe the effectiveness of aripiprazole (APZ) in the treatment of children with bipolar disorders suffering from manic symptomatology.
Symptomatic outpatients (Young Mania Rating Scale [YMRS] score ≥15) meeting strict, unmodified, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic symptom criteria for a bipolar disorder, ages 4–9 years, were eligible. Subjects were treated prospectively with flexible doses of APZ (maximum daily dose of 15 mg/day), for up to 16 weeks or until a priori response criteria were met. Outcome measures included the YMRS, Clinical Global Impressions Scale-Severity, Children's Global Assessment Scale (CGAS), and the Children's Depression Rating Scale-Revised (CDRS-R). A priori response criteria consisted of 3 of 4 consecutive weeks with (1) CDRS-R <29; (2) YMRS <10; and (3) CGAS >50.
Ninety-six children (62 males; mean age of 6.9 (SD = 1.7), received APZ for an average length of treatment of 12.5 (SD = 3.9) weeks. Significant improvements in YMRS, CDRS-R, CGAS, and Clinical Global Impressions Scale-Severity scores (p < 0.001) were noted at the end of study participation. Sixty of the subjects (62.5%) met a priori response criteria at study's end. The most common side effects noted were stomachache, increased appetite, and headache. Two subjects were removed from the study due to side effects [epistaxis (n = 1); akathisia (n = 1)]. Subjects experienced an average weight gain of 2.4 (SD = 1.9) kg.
APZ may be effective in the acute treatment of symptoms of children with bipolar illnesses.
To compare attention-deficit hyperactivity disorder (ADHD), bipolar spectrum disorders (BPSD), and comorbidity in the Longitudinal Assessment of Manic Symptoms (LAMS) study.
Children ages 6–12 were recruited at first visit to clinics associated with four universities. A BPSD diagnosis required that the patient exhibit episodes. Four hypotheses were tested: (i) children with BPSD + ADHD would have younger age of mood symptom onset than those with BPSD but no ADHD; (ii) children with BPSD + ADHD would have more severe ADHD and BPSD symptoms than those with only one disorder; (iii) global functioning would be more impaired in children with ADHD + BPSD than children with either diagnosis alone; and (iv) the ADHD + BPSD group would have more additional diagnoses.
Of 707 children, 538 had ADHD, 162 had BPSD, 117 had both ADHD and BPSD, and 124 had neither. Comorbidity (16.5%) was slightly less than expected by chance (17.5%). Age of mood symptom onset was not different between the BPSD + ADHD group and the BPSD-alone group. Symptom severity increased and global functioning decreased with comorbidity. Comorbidity with other disorders was highest for the ADHD + BPSD group, but higher for the ADHD-alone than the BPSD-alone group. Children with BPSD were four times as likely to be hospitalized (22%) as children with ADHD alone.
The high rate of BPSD in ADHD reported by some authors may be better explained as a high rate of both disorders in child outpatient settings rather than ADHD being a risk factor for BPSD. Co-occurrence of the two disorders is associated with poorer global functioning, greater symptom severity, and more additional comorbidity than for either single disorder.
ADHD; bipolar; comorbidity; impairment; severity
Four subtypes of bipolar disorder (BP) – bipolar I, bipolar II, cyclothymia and bipolar not otherwise specified (NOS) – are defined in DSM-IV-TR. Though the diagnostic criteria for each subtype are intended for both adults and children, research investigators and clinicians often stray from the DSM when diagnosing pediatric bipolar disorder (PBD) (Youngstrom, 2009), resulting in a lack of agreement and understanding regarding the PBD subtypes.
The present study uses the diagnostic validation method first proposed by Robins and Guze (1970) to systematically evaluate cyclothymic disorder as a distinct diagnostic subtype of BP. Using a youth (ages 5–17) outpatient clinical sample (n=827), participants with cyclothymic disorder (n=52) were compared to participants with other BP spectrum disorders and to participants with non-bipolar disorders.
Results indicate that cyclothymic disorder shares many characteristics with other bipolar subtypes, supporting its inclusion on the bipolar spectrum. Additionally, cyclothymia could be reliably differentiated from non-mood disorders based on irritability, sleep disturbance, age of symptom onset, comorbid diagnoses, and family history.
There is little supporting research on cyclothymia in young people; these analyses may be considered exploratory. Gaps in this and other studies are highlighted as areas in need of additional research.
Cyclothymic disorder has serious implications for those affected. Though it is rarely diagnosed currently, it can be reliably differentiated from other disorders in young people. Failing to accurately diagnose cyclothymia, and other subthreshold forms of bipolar disorder, contributes to a significant delay in appropriate treatment and may have serious prognostic implications.
cyclothymic disorder; pediatric bipolar disorder; validation; Robins and Guze
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.
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.
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.
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.
To assess the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) combined with stimulants (ie, methylphenidate or amphetamine) for attention-deficit/hyperactivity disorder (ADHD).
PATIENTS AND METHODS:
In this phase 3, double-blind, placebo-controlled trial, children and adolescents with hyperactive- or combined-subtype ADHD who had an inadequate response to their stable stimulant regimen were randomized to receive CLON-XR or placebo in combination with their baseline stimulant medication. Predefined efficacy measures evaluated change from baseline to week 5. Safety was assessed by spontaneously reported adverse events, vital signs, electrocardiogram recordings, and clinical laboratory values. Improvement from baseline for all efficacy measures was evaluated using analysis of covariance.
Of 198 patients randomized, 102 received CLON-XR plus stimulant and 96 received placebo plus stimulant. At week 5, greater improvement from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score (95% confidence interval: −7.83 to −1.13; P = .009), ADHD-RS-IV hyperactivity and inattention subscale scores (P = .014 and P = .017, respectively), Conners' Parent Rating Scale scores (P < .062), Clinical Global Impression of Severity (P = .021), Clinical Global Impression of Improvement (P = .006), and Parent Global Assessment (P = .001) was observed in the CLON-XR plus stimulant group versus the placebo plus stimulant group. Adverse events and changes in vital signs in the CLON-XR group were generally mild.
The results of this study suggest that CLON-XR in combination with stimulants is useful in reducing ADHD in children and adolescents with partial response to stimulants.
α2-adrenergic agonist; attention-deficit/hyperactivity disorder; clonidine–hydrochloride extended-release tablets; psychostimulant
Pediatric bipolar disorder (PBD) involves a potent combination of mood dysregulation and interpersonal processes, placing these youth at significantly greater risk of suicide. We examined the relationship between suicidal behavior, mood symptom presentation, family functioning, and quality of life (QoL) in youth with PBD.
Participants were 138 youths aged 5–18 years presenting to outpatient clinics with DSM-IV diagnoses of bipolar I disorder (n = 27), bipolar II disorder (n = 18), cyclothymic disorder (n = 48), and bipolar disorder not otherwise specified (n = 45).
Twenty PBD patients had lifetime suicide attempts, 63 had past or current suicide ideation, and 55 were free of suicide ideation and attempts. Attempters were older than nonattempters. Suicide ideation and attempts were linked to higher depressive symptoms, and rates were even higher in youths meeting criteria for the mixed specifier proposed for DSM-5. Both suicide ideation and attempts were associated with lower youth QoL and poorer family functioning. Parent effects (with suicidality treated as outcome) and child effects (where suicide was the predictor of poor family functioning) showed equally strong evidence in regression models, even after adjusting for demographics.
These findings underscore the strong association between mixed features and suicidality in PBD, as well as the association between QoL, family functioning, and suicidality. It is possible that youths are not just a passive recipient of family processes, and their illness may play an active role in disrupting family functioning. Replication with longitudinal data and qualitative methods should investigate both child and parent effect models.
bipolar disorder; family; quality of life; suicide
To describe service utilization of a cohort of children with emotional and behavioral disorders who visited outpatient mental health clinics in four Midwest cities.
Data come from the Longitudinal Assessment of Manic Symptoms (LAMS) Study. 707 youth (ages 6–12 years) and their parents completed diagnostic assessments, demographic information and an assessment of mental health service utilization. Analyses examined the relationship of demographics, diagnoses, impairment, and comorbidity to the type and level of services utilized.
Service utilization is multimodal with half of the youth receiving both outpatient and school services during their lifetime. Non-need factors including age, sex, race, and insurance, were related to types of services used. Youth diagnosed with a bipolar spectrum disorder had higher utilization of inpatient services and two or more services at one time compared to youth diagnosed with depressive or disruptive disorders. More than half of youth diagnosed with bipolar or depressive disorders had received both medication and therapy during their lifetime whereas for youth diagnosed with a disruptive disorder therapy only was more common. Impairment and comorbidity were not related to service utilization.
Use of mental health services for children begins at a very young age and occurs in multiple service sectors. Type of service use is related to insurance and race/ethnicity, underscoring the need for research on treatment disparities. Contrary to findings from results based on administrative data, medication alone was infrequent. However, the reasonably low use of combination therapy suggests that clinicians and families need to be educated on the effectiveness of multimodal treatment.
Bipolar Disorder; Mania; Child; Adolescent; Services