[show abstract][hide abstract] ABSTRACT: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders.
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.
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.
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.
Journal of the American Academy of Child and Adolescent Psychiatry 06/2010; 49(6):583-94; quiz 632. · 4.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Metformin was assessed as an interventional medication for weight gain in children and adolescents taking atypical antipsychotic agents.
A 12-week open-label trial was conducted to evaluate metformin's effectiveness and safety for weight management. Eleven subjects, ages 10-18 years, participated in the study. Each subject received metformin orally up to 2000 mg/day. Primary outcome measures included weight, body mass index (BMI), and waist circumference. Secondary outcome measures included serum glucose, insulin, and fasting lipid profile. Changes in weight, BMI, waist, and metabolic profile were obtained by using repeated measures of covariance.
The mean reduction in weight, waist, BMI, serum glucose, and serum insulin was not statistically significant. However, 5 out of 11 patients lost weight (mean, -2.82 kg +/- 7.25), and overall the sample did not continue to gain weight. There was a significant decrease in triglyceride levels. Metformin was fairly well tolerated.
Preliminary data suggests that metformin may safely and effectively improve the triglyceride profile. However, contrary to study hypotheses, weight, waist, and BMI reduction were not statistically significant. Future double-blind studies with larger sample sizes and of longer duration are warranted to assess more fully the safety and efficacy of this intervention.
Journal of child and adolescent psychopharmacology 07/2009; 19(3):275-9. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
American Journal of Psychiatry 10/2008; 165(11):1420-31. · 14.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Children with psychiatric illness are at greater risk for obesity than those in the general population. In part, this greater risk is due to the escalating use of psychotropic medications. Second-generation antipsychotics effectively treat mental illness but are associated with weight gain. Data for management of obesity in this population is lacking.
Articles on obesity, mental illness, and obesity management were reviewed. Keywords included children, adolescents, obesity, weight gain, psychiatric illness, therapy, treatment, and antipsychotic.
For pediatric obesity, educational, nutritional, behavioral, and family-based interventions were identified as nonpharmacological interventions. All nonpharmacological modalities indicate modest to moderate success in weight control or loss. Pharmacological agents, alone or with diet and exercise, appear promising in obesity management.
Since there are limited intervention studies available for obese children with psychiatric illness, general childhood obesity studies may be referenced for trials in this population. Long-term efficacy and safety of these interventions are not yet available. Methodological constraints of prior studies include small sample sizes and the absence of randomized, placebo-controlled, and longitudinal trials - highlighting the need for further trials addressing these issues. Clinical monitoring and management of medication-induced obesity remains an important public health concern.
Harvard Review of Psychiatry 01/2008; 16(2):69-79. · 3.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders.
Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites. Diagnosis was made via structured and clinical interviews. Assessments of psychiatric symptoms and social and global functioning were included.
A total of 119 youths were enrolled. The mean age at illness onset was 11.1 +/- 3.5 years. Patients with SZ and schizoaffective disorder had similar ratings on the Positive and Negative Symptom Scale, Brief Psychiatric Rating Scale for Children, and Clinical Global Impression-Severity Scale. The overall level of functioning was similar in the two groups. A comparison to published reports of adults with SZ indicates that these youths may have more severe symptoms based on results of the Positive and Negative Symptom Scale.
This is one of the largest samples of youths with SZ spectrum disorders studied to date and the largest assessment of youths with schizoaffective disorder. High rates of symptoms and general psychopathology were noted. There was a substantial degree of social and functional impairment. The symptom profiles are consistent with, but more severe than, those reported in the adult literature.
Journal of the American Academy of Child & Adolescent Psychiatry 09/2007; 46(8):979-88. · 6.97 Impact Factor