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DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II, cyclothymic disorder and bipolar not otherwise specified (NOS). However, cyclothymic disorder in children is rarely researched, or often subsumed in an "NOS" category. The present study tests the replicability of findings from an earlier study, and expands on the criterion validity of cyclothymic disorder in youth. Using the Robins and Guze (1970) framework we examined the validity of cyclothymic disorder as a subtype of BP. Using a youth (ages 5-17) outpatient clinical sample (N = 894), participants with cyclothymic disorder (n = 53) were compared to participants with other BP spectrum disorders (n = 399) and to participants with non-bipolar disorders (n = 442). Analyses tested differences in youth with cyclothymic disorder and bipolar disorder not otherwise specified who do, and those who do not, have a parent with BP. Compared to youth with non-bipolar disorders, youth with cyclothymic disorder had higher irritability (p less than 0.001), more comorbidity (p less than 0.001), greater sleep disturbance (p less than 0.005), and were more likely to have a family history of BP (p less than 0.001). Cyclothymic disorder was associated with a younger age of onset compared to depression (p less than 0.001) and bipolar II (p = 0.05). Parental BP status was not significantly associated with any variables. Results support that cyclothymic disorder belongs on the bipolar spectrum. Epidemiological studies indicate that cyclothymic disorder is not uncommon and involves significant impairment. Failing to differentiate between cyclothymic disorder and bipolar NOS limits our knowledge about a significant proportion of cases of bipolarity.

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 authors of current study examined both sampling and context effects of a brief measure of pediatric mania. Caregivers of 813 youths completed the parent-reported version of the General Behavior Inventory (PGBI) at an academic medical center sample enriched for mood disorders. Caregivers of 481 youths completed the PGBI at a community mental health center. Caregivers of 799 youths completed 10 items extracted from the PGBI at a community setting. Caregivers of 159 youths completed both versions of the PGBI and a semistructured 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 10 extracted items discriminated bipolar disorder from nonbipolar behavior 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. (Contains 2 figures and 4 tables.)

Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase. Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of DVPX (50 micrograms/mL) or Li (0.6 mmol/L). Secondary measures included pill count, patient/parent report, and clinical judgment. Correlates of adherence, including patient characteristics, medication side effects, and family variables, were evaluated. Results: One hundred seven patients (70 males and 37 females) were studied. The proportion of serum concentrations in the therapeutic range across the study period was 0.84 for DVPX and 0.66 for Li. Maternal (r = -0.31; p less than 0.01) and paternal (r = -0.44; p less than 0.01) hospitalization for a psychiatric disorder and less adaptive family functioning (r= -0.26; p less than 0.05) related to treatment nonadherence for DVPX. Better treatment adherence to DVPX (r = 0.21; p less than 0.05) and Li (r = 0.23; p less than 0.05) was associated with a greater number of side effects, whereas male sex was associated with worse adherence to both DVPX (r= -0.24; p less than 0.05) and Li (r = -0.22; p less than 0.05) pharmacotherapy. Clinical response to treatment correlated with adherence to DVPX treatment (r = 0.33; p less than 0.01). Conclusions: Nonadherence may limit the statistical power of treatment efficacy studies and the effectiveness of pharmacotherapy treatment for juvenile BPD and necessitate strategies to evaluate and enhance levels of treatment adherence. (Contains 5 tables.)

Abstract Background The objective of this study was to examine whether fluoxetine was superior to placebo in the acute amelioration of depressive symptomatology in adolescents with depressive illness and a comorbid substance use disorder. Methods Eligible subjects ages 12–17 years with either a current major depressive disorder (MDD) or a depressive disorder that were also suffering from a comorbid substance-related disorder were randomized to receive either fluoxetine or placebo in this single site, 8-week double-blind, placebo-controlled study. The primary outcome analysis was a random effects mixed model for repeated measurements of Children's Depression Rating Scale-Revised (CDRS-R) scores compared between treatment groups across time. Results An interim analysis was performed after 34 patients were randomized. Based on the results of a futility analysis, study enrollment was halted. Twenty-nine males and 5 females were randomized to receive fluoxetine (n = 18) or placebo (n = 16). Their mean age was 16.5 (1.1) years. Overall, patients who received fluoxetine and placebo had a reduction in CDRS-R scores. However, there was no significant difference in mean change in CDRS-R total score in those subjects treated with fluoxetine and those who received placebo (treatment difference = 0.19, S.E. = 0.58, F = 0.14, p = .74). Furthermore, there was not a significant difference in rates of positive urine drug toxicology results between treatment groups at any post-randomization visit (F = 0.22, df = 1, p = 0.65). The main limitation of this study is its modest sample size and resulting low statistical power. Other significant limitations to this study include, but are not limited to, the brevity of the trial, high placebo response rate, limited dose range of fluoxetine, and the inclusion of youth who met criteria for depressive disorders other than MDD. Conclusion Fluoxetine was not superior to placebo in alleviating depressive symptoms or in decreasing rates of positive drug screens in the acute treatment of adolescents with depression and a concomitant substance use disorder.

Abstract Background Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. Methods Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. Results The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites. Conclusion These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness. Trial Registration NCT00442039