Ann E. Maloney

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study

OBJECTIVE Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. METHOD This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. RESULTS In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. CONCLUSIONS Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder. The safety findings related to weight gain and metabolic problems raise important public health concerns, given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders.

Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study.

OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. METHOD Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703.

Games for Health for Children - Current Status and Needed Research

Videogames for health (G4H) offer exciting, innovative, potentially highly effective methods for increasing knowledge, delivering persuasive messages, changing behaviors, and influencing health outcomes. Although early outcome results are promising, additional research is needed to determine the game design and behavior change procedures that best promote G4H effectiveness and to identify and minimize possible adverse effects. Guidelines for ideal use of different types of G4H by children and adolescents should be elucidated to enhance effectiveness and minimize adverse effects. G4H stakeholders include organizational implementers, policy makers, players and their families, researchers, designers, retailers, and publishers. All stakeholders should be involved in G4H development and have a voice in setting goals to capitalize on their insights to enhance effectiveness and use of the game. In the future, multiple targeted G4H should be available to meet a populations diverse health needs in developmentally appropriate ways. Substantial, consistent, and sophisticated research with appropriate levels of funding is needed to realize the benefits of G4H.

Parental and environmental factors associated with physical activity among children participating in an active video game.

Purpose: Parental and intervention-specific environmental supports were examined as potential reinforcers for physical activity and use of a video game, Dance Dance Revolution (DDR), among a cohort of 7- to 8-year-old children. Methods: Sixty children were randomized to an intervention (n = 40) or a control (n = 20) group. Physical activity was measured with accelerometry and DDR logs. Parental support for their child’s physical activity was assessed via a questionnaire. DDR-specific environmental supports were captured on an environmental home screen and the DDR log. Results: At baseline, the absence of other video games and parent DDR participation was associated with child participation in DDR. At follow-up, DDR participation of siblings and friends was associated with child participation in DDR. Conclusion: The primary findings of this study suggest that parental and peer participation in DDR may play a role in children’s initial and sustained participation in DDR.

Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain

Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that risperidone treatment can have negative skeletal consequences by direct activation of osteoclast activity and by indirect non-cell autonomous mechanisms. Our findings further support the tenet that the negative side effects of SGAs on bone mass should be considered when weighing potential risks and benefits, especially in children and adolescents who have not yet reached peak bone mass.

Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

Background Severe and persistent mental illnesses in children and adolescents, such as early- onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP. Methods PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined. Results Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare. Conclusions The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.

Can Dance Exergames Boost Physical Activity as a School-Based Intervention?

BACKGROUND Children need opportunities to have physical activity (PA). Using exergames could be a feasible and acceptable way to boost PA in middle schools. Our goal was to increase PA by 40 minutes per week and to determine how much time, if any, was spent in moderate-to-vigorous PA (MVPA). SUBJECTS AND METHODS Eighty-four middle school youth were in a pilot study for 20 weeks: half in the Generation Fit (GenFit) intervention group and half in the control group. The GenFit group played the exergame for the first 10 weeks (Session 1), and the control group joined from 10 to 20 weeks (Session 2). The main outcome was exergaming time per student per week. RESULTS Fifty-eight students completed the pilot after 26 youth at School C were excluded for administrative reasons. Of those remaining, 40 students at School A and 18 students at School B, the average age of the sample was 13.7 years (SD=0.6), and average body mass index percentile was close to 70. During Session 1, the average dance time per child was 49 minutes per week, versus 54 minutes per week in Session 2. Mean body mass index percentile decreased by 5.6 for children who participated in GenFit, compared with 0.2 for children in the control group. At end point, accelerometers showed over half of the dance time was spent in MVPA. Qualitative data showed that most children found the exergame acceptable. CONCLUSIONS A dance exergame in middle schools offered opportunities for PA. About half of the exergame time was spent in MVPA. Exergames may be feasible and acceptable in middle schools to boost PA, and access could provide a way for schools to support the health of students.

Gaming, Adiposity, and Obesogenic Behaviors among Children

Videogames in general have been maligned for causing obesity because of their inherent sedentariness, whereas exergames have been both maligned for requiring low levels of activity and extolled for requiring physical activity to move game play along. The intensity and duration of physical activity resulting from exergame play have shown varying results, and they have been explored for use in obesity treatment and prevention, primarily among children. Other videogames have been developed and tested to help children change their diet and physical activity practices with various outcomes. As a field of inquiry, we are in the earliest stages of understanding how, or under what circumstances, videogames can influence all these behavioral and health outcomes. To deal with these complexities, we have assembled a group of investigators who have made important, but diverse, contributions to this research agenda and asked them to address five key child obesity-related issues in a Roundtable format. Brief biosketches are presented at the end of this article.

Empirical evidence for psychopharmacologic treatment in early-onset psychosis and schizophrenia.

Psychotic symptoms presenting in youth can be clinically complex and require that a child and adolescent psychiatrist use significant skill in making a diagnosis and initiating treatment. There are a number of illnesses to rule out before making a diagnosis of early-onset schizophrenia in particular. Psychosis in youth has significant associated morbidity and places high demands not only on families but also on the medical and educational systems. More effective pharmacologic and nonpharmacologic treatments for psychosis are needed. Nonpharmacologic therapies targeting relatively treatment-resistant domains of dysfunction such as neurocognition are also necessary as adjunctive treatments to our extant pharmacologic agents.

Pediatric Obesity: A Review for the Child Psychiatrist

Child and adolescent psychiatrists frequently encounter children who are obese in their practices and may be asked to work alongside primary care physicians and other specialists who treat youngsters with obesity. To offer expert consultation, they must understand all aspects of the pediatric obesity epidemic. By summarizing the relevant endocrinology, cardiology, nutrition, exercise science, and public health literature, this review of pediatric obesity assesses the epidemics background, delineates the challenges of clinical care, and appraises the therapeutic recommendations for this population of patients and their families.