Difficulties in emotional regulation and substance use disorders: a controlled family study of bipolar adolescents.

BACKGROUND: Self-regulatory mechanisms appear etiologically operant in the context of both substance use disorders (SUD) and bipolar disorder (BD), however, little is known about the role of deficits in emotional self-regulation (DESR) as it relates to SUD in context to mood dysregulation. To this end, we examined to what extent DESR was associated with SUD in a high-risk sample of adolescents with and without BD. METHODS: 203 families were assessed with a structured psychiatric interview. Using the Child Behavior Checklist (CBCL), a subject was considered to have DESR when he or she had an average elevation of 1 standard deviation (SD) above the norm on 3 clinical scale T scores (attention, aggression, and anxiety/depression; scores: 60 × 3 ≥ 180). RESULTS: Among probands and siblings with CBCL data (N=303), subjects with DESR were more likely to have any SUD, alcohol use disorder, drug use disorder, and cigarette smoking compared to subjects with scores <180 (all p values <0.001), even when correcting for BD. We found no significant differences in the risk of any SUD and cigarette smoking between those with 1SD and 2SD above the mean (all p values >0.05). Subjects with cigarette smoking and SUD had more DESR compared to those without these disorders. CONCLUSIONS: Adolescents with DESR are more likely to smoke cigarettes and have SUD. More work is needed to explore DESR in longitudinal samples.

A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents.

RATIONALE: Treatment studies for the management of pediatric bipolar disorder are limited. OBJECTIVES: This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders. METHODS: An 8-week, prospective, open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders (depression, psychosis, attention-deficit/hyperactivity disorder [ADHD]). Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impression scale (CGI), Children's Depression Rating Scale-Revised (CDRS-R), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. RESULTS: Fifteen youth with bipolar spectrum disorders (YMRS at entry: 32.8 ± 6.1) were enrolled in the study and 11 (73 %) completed the 8-week trial. The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects. Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores (-18.7 ± 13.9, p < 0.001) at endpoint. Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms. Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight (4.1 ± 5.5 lb) were substantial. CONCLUSIONS: Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth. Future placebo-controlled studies are warranted to confirm these findings.

A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder.

OBJECTIVES: Due to concerns about the safety of stimulants for ADHD, novel assessments of the cardiopulmonary impact of these agents are needed. METHODS: An open design of lisdexamfetamine (LDX) in 15 adults with DSM-IV ADHD. Following a psychiatric evaluation and medical history, subjects underwent echocardiography (TTE) and cardiopulmonary exercise testing (CPET). LDX was titrated to 70 mg daily over 6 weeks, followed by monthly visits to 6 months. Change in TTE and CPET measures were examined following up to 6 months of LDX. RESULTS: At endpoint, there were no significant alterations in indices of cardiac systolic performance, or in metabolic and ventilatory variables at maximum exertion (P values >0.05). We found significant mean changes in resting LV systolic dimension and Doppler diastolic indices. Change in heart rate recovery at 1 min met statistical significance (P = 0.05). CONCLUSIONS: We did not detect clinically meaningful changes in cardiac structure and function or in metabolic and ventilatory variables at maximum exertion in ADHD adults receiving open LDX. The clinical significance of changes in resting LV dimension and indices of diastolic function are not in the direction of cardiomyopathy. Future large sample controlled study can examine these findings, as well as stimulants' impact on heart rate recovery.

Cardiovascular risk of stimulant treatment in pediatric attention-deficit/hyperactivity disorder: update and clinical recommendations.

OBJECTIVE: This review provides an update on the cardiovascular impact of therapeutic stimulant-class medication for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHOD: Relevant clinical literature was ascertained using PubMed searches limited to human studies and the English language as of May 2011. Current practice guidelines and consensus statements also were reviewed. RESULTS: Stimulant-class medications for healthy children and adolescents with ADHD are associated with mean elevations in blood pressure (≤5 mmHg) and heart rate (≤10 beats/min) without changes in electrocardiographic parameters. A subset (5-15%) of children and adolescents treated may have a greater increase in heart rate or blood pressure at a given assessment or may report a cardiovascular-type complaint during stimulant treatment. It is extremely rare for a child or adolescent receiving stimulant medication to have a serious cardiovascular event during treatment, with the risk appearing similar to groups of children not receiving stimulant medication. CONCLUSIONS: Clinicians should adhere to current recommendations regarding the prescription of stimulant medications for youth with ADHD. Scientific inquiry is indicated to identify patients at heightened risk and to continue surveillance for the longer-term cardiovascular impact of these agents.