Ginger E. Nicol

Metabolic Screening in Children Receiving Antipsychotic Drug Treatment

OBJECTIVES To estimate metabolic screening rates, predictors of screening, and incidence of metabolic disturbances in children initiating second-generation antipsychotic (SGA) drug treatment. DESIGN A retrospective, new-user cohort study (between July 1, 2004, and June 30, 2006) using Medicaid claims data. SETTINGS California, Missouri, and Oregon. PATIENTS A total of 5370 children (aged 6-17 years) without diabetes mellitus taking SGA drugs and 15,000 children without diabetes taking albuterol (control individuals) [corrected] but no SGA drugs. INTERVENTION Findings 1 year after recommendations from the American Diabetes Association and American Psychiatric Association called for metabolic screening of patients receiving SGA drugs. OUTCOME MEASURES Serum glucose and lipid testing, 6-month incidence of diabetes, and dyslipidemia disturbances. RESULTS Glucose screening was performed in 1699 (31.6% [95% confidence interval (CI), 30.4%-32.9%]) SGA-treated children vs 1891 (12.6% [12.1%-13.2%]) control individuals. Lipid testing was performed in 720 (13.4% [95% CI, 12.5%-14.4%]) SGA-treated children vs 458 (3.1% [2.8%-3.3%]) controls. In multivariate logistic regression analysis, children with serious and/or multiple psychiatric diagnoses and those who used health care services more intensively were more likely to receive metabolic screening. The case incidence of glucose and lipid disorders was higher in SGA-treated vs albuterol-treated children (8.9 per 1000 children [95% CI, 6.6%-11.8%] vs 4.9 per 1000 children [3.9%-6.2%]; and 9.7 per 1000 children [95% CI, 7.2%-12.7%] vs 4.6 per 1000 children [95% CI, 3.6%-5.8%], respectively). CONCLUSION Most children starting treatment with SGA medications in this public sector sample did not receive recommended glucose and lipid screening.

Recent advances in understanding and mitigating adipogenic and metabolic effects of antipsychotic drugs

Although offering many benefits for several psychiatric disorders, antipsychotic drugs (APDs) as a class have a major liability in their tendency to promote adiposity, obesity, and metabolic dysregulation in an already metabolically vulnerable population. The past decade has witnessed substantial research aimed at investigating the mechanisms of these adverse effects and mitigating them. On July 11 and 12, 2011, with support from 2 NIH institutes, leading experts convened to discuss current research findings and to consider future research strategies. Five areas where significant advances are being made emerged from the conference: (1) methodological issues in the study of APD effects; (2) unique characteristics and needs of pediatric patients; (3) genetic components underlying susceptibility to APD-induced metabolic effects; (4) APD effects on weight gain and adiposity in relation to their acute effects on glucose regulation and diabetes risk; and (5) the utility of behavioral, dietary, and pharmacological interventions in mitigating APD-induced metabolic side effects. This paper summarizes the major conclusions and important supporting data from the meeting.

Cardiometabolic outcomes in children and adolescents following discontinuation of long-term risperidone treatment

OBJECTIVE Second-generation antipsychotics (SGAs) cause weight gain and cardiometabolic abnormalities in children and adolescents. Less well-investigated is the outcome of these adverse events following SGA discontinuation, which we examined. METHODS Medically healthy 7 to 17-year-old patients treated with risperidone for ≥6 months were enrolled and returned for follow-up, 1.5 years later. Treatment history was extracted from the medical and pharmacy records. Anthropometric and laboratory measurements were obtained at each research visit. Multivariable linear regression analysis and Fishers exact test were used to compare participants who remained on risperidone at follow-up (Risp Cont Group) with those who had discontinued SGA treatment (SGA Disc Group) and those who had switched to another SGA (SGA Cont Group). Correlational analyses examined the association between change in age-sex specific body mass index (BMI) z score between study entry and follow-up and change in cardiometabolic outcomes. RESULTS The sample consisted of 101 participants (93% male) with a mean age of 11.7±2.6 years at study entry. The majority had an externalizing disorder and received 0.03±0.02 mg/kg/day of risperidone, for 2.5±1.6 years. At follow-up, 18% (n=18) were in the SGA Disc Group and 9% (n=9) were in the SGA Cont Group. BMI z score decreased in the SGA Disc Group, remained unchanged in the Risp Cont Group (n=74), and increased in the SGA Cont Group. Importantly, the change in BMI z score between study entry and follow-up was significantly correlated with the change in systolic and diastolic blood pressure z scores, heart rate, waist circumference, percent body fat, inflammatory markers, fasting total insulin, homeostatic model assessment insulin resistance index (HOMA-IR), C-peptide, total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, triglycerides, triglycerides/HDL ratio, and leptin. CONCLUSIONS Following several years of treatment, risperidone discontinuation is associated with a reversal of the excessive weight gain, mediated by a negative energy balance, and a corresponding improvement in cardiometabolic parameters.

The Prevalence of Past 12-Month and Lifetime DSM-IV Eating Disorders by BMI Category in US Men and Women

OBJECTIVE This study aims to determine whether the prevalence of lifetime and past 12-month DSM-IV eating disorders (ED) diagnoses differed by body mass index category among men and women in a general population sample. METHODS Data from the Collaborative Psychiatric Epidemiology Surveys (n = 12 337 adults) were analysed using logistic regression. Analyses were conducted separately by gender. RESULTS Lifetime ED prevalence was 2.22% in men and 4.93% in women. In both genders, the prevalence of any lifetime and past 12-month ED, binge eating disorder and recurrent binge eating was highest among obese individuals. Among obese men and women, lifetime and past 12-month ED prevalence was highest among those with class III obesity. CONCLUSION Eating disorders were most prevalent among high-weight individuals. This information is important for planning targeted public health ED and obesity prevention and intervention activities, as well as for informing the clinical care of obese individuals. Copyright

Psychotropic Drug Use Among Preschool Children in the Medicaid Program From 36 States

OBJECTIVES We determined the prevalence of and indications for psychotropic medication among preschool children in Medicaid. METHODS We obtained 2000 to 2003 Medicaid Analytic Extract data from 36 states. We followed children in 2 cohorts, born in 1999 and 2000, up to age 4 years. We used logistic regression to model odds of receiving medications for (1) attention-deficit disorder/attention-deficit hyperactivity disorder, (2) depression or anxiety, and (3) psychotic illness or bipolar. RESULTS Overall, 1.19% of children received at least 1 psychotropic drug. Medications for attention-deficit disorder/attention-deficit hyperactivity disorder treatment were most common (0.61% of all children), followed by depression or anxiety (0.59%) and psychotic illness or bipolar (0.24%). Among children, boys, those of other or unknown race compared with White, and those with other insurance compared with fee for service-only had higher odds of receiving a prescription (odds ratio [OR]=1.80 [95% confidence interval (CI)=1.74, 1.86], 1.75 [corrected] [1.66, 1.85], and 1.14 [1.01, 1.28], respectively), whereas Black and Hispanic children had lower odds (OR=0.51 [95% CI=0.48, 0.53] and 0.37 [0.34, 0.39], respectively). CONCLUSIONS Preschoolers are receiving psychotropic medications despite limited evidence supporting safety or efficacy. Future research should focus on implementing medication use practice parameters in infant and toddler clinics, and expanding psychosocial interventions for young children with behavioral problems.

Implementation of a Glucose Screening Program Based on Diffusion of Innovation Theory Methods

There is public health interest in the identification and treatment of modifiable cardiometabolic risk factors among patients treated with antipsychotic medications. However, best-practice screening recommendations endorsed by multiple medical organizations have not translated into real-world clinical practice. Quality improvement strategies may help to address the gap between policy and implementation. This column describes the successful implementation of a best-practice glucose screening program in a large network of community mental health centers that was based on Six Sigma and diffusion of innovation theory.

Correlates of weight gain during long-term risperidone treatment in children and adolescents

BackgroundMost clinical trials of antipsychotics in children are brief, failing to address their long-term safety, particularly when taken concurrently with other psychotropics. This hypothesis-generating analysis evaluates potential correlates of weight gain in children receiving extended risperidone treatment.MethodsMedically healthy 7–17 year-old patients treated with risperidone for six months or more were enrolled. Anthropometric measurements were conducted. Developmental and medication history was obtained from the medical record. Information related to birth weight, dietary intake, physical activity, and parental weight was collected. Mixed regression analyses explored the contribution of various demographic and clinical factors to age- and sex-adjusted weight and body mass index (BMI) z scores over the treatment period.ResultsThe sample consisted of 110 patients (89% males) with a mean age of 11.8 years (sd = 2.9) upon enrollment. The majority had an externalizing disorder and received 0.03 mg/kg/day (sd = 0.02) of risperidone, for 2.5 years (sd = 1.7), to primarily target irritability and aggression (81%). Polypharmacy was common with 71% receiving psychostimulants, 50% selective serotonin reuptake inhibitors (SSRIs), and 32% α2-agonists. Weight and BMI z score were positively correlated with baseline weight at the start of risperidone, treatment duration, and the weight-adjusted dose of risperidone but inversely associated with the weight-adjusted dose of psychostimulants and the concurrent use of SSRIs and α2-agonists. The effect of risperidone dose appeared to attenuate as treatment extended while that of psychostimulants became more significant. The rate of change in weight (or BMI) z score prior to and within the first 12 weeks of risperidone treatment did not independently predict future changes neither did birth weight, postnatal growth, dietary intake, physical activity, or parental weight.ConclusionsThis comprehensive analysis exploring correlates of long-term weight (or BMI) change in risperidone-treated youths revealed that pharmacotherapy exerts significant but complex effects.Trial RegistrationNot applicable.

The Role of Clinical Setting and Management Approach in Metabolic Testing Among Youths and Adults Treated With Antipsychotics

OBJECTIVE This study compared metabolic screening among patients who received antipsychotic treatment at community mental health centers (CMHCs), with or without case management, and patients treated elsewhere. METHODS Rates of glucose and lipid testing among youths and adults in Missouri Medicaid (N=9,473) who received antipsychotic treatment at CMHCs, with and without case management, were evaluated. Multivariable logistic regressions determined which characteristics were independently associated with metabolic testing. RESULTS A total of 37.0% and 17.3% of youths and 68.7% and 34.9% of adults had glucose and lipid testing, respectively. Compared with treatment elsewhere, treatment at CMHCs, with or without case management, respectively, was associated with higher odds of glucose testing (youths, adjusted odds ratio [AOR]=1.68 and 1.89; adults, AOR=1.43 and 1.44) and lipid testing (youths, AOR=2.40 and 2.35; adults, AOR=1.97 and 1.48). CONCLUSIONS CMHCs had higher rates of metabolic testing, possibly reflecting Missouris efforts to promote testing in these settings.

Getting to More Effective Weight Management in Antipsychotic-Treated Youth: A Survey of Barriers and Preferences

BACKGROUND Mentally ill youth are at risk for developing obesity, especially when they require antipsychotic treatment; moreover, they may face unique challenges in adhering to behavioral weight loss interventions. The aims of this project were to characterize the challenges families of youth with psychiatric disorders face when engaging in weight loss treatment and to gather information on attitudes and preferences for weight management interventions in this population. METHODS We devised a telephone survey to evaluate caregiver-perceived barriers/challenges to and preferences for behavioral weight loss treatment in overweight or obese mentally ill youth ages 6-18 treated with an antipsychotic agent in an outpatient setting. RESULTS A total of 26 parents or primary caregivers completed the survey. The most commonly cited barriers to participation in physical activity (PA) and maintaining a healthy diet were childs dislike of PA and childs preference for energy-dense foods, respectively, which were impacted by psychiatric symptoms. Preferences for weight loss treatment included individualized, prescribed meal plans and shopping lists, and exercise support/demonstration, with a preference for Internet or cell phone applications to help with monitoring food intake and exercise. CONCLUSIONS These results suggest that targets for obesity treatment in this population include individualized, specific support that takes into account the childs motivation, which is effected by psychiatric symptoms. Tools for providing support may include the use of telehealth visits and mobile device applications for self-monitoring.

Review: Children and adolescents with schizophrenia spectrum disorders respond to antipsychotics, but are susceptible to adverse events

ED FROM Kumra S, Oberstar JV, Sikich L, et al. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull 2008;34:60–71. Correspondence to: Sanjiv Kumra, Division of Child and Adolescent Psychiatry, University of Minnesota Medical School, 2450 Riverside Avenue, F256/2B, Minneapolis, MN 55454, USA; kumra002@umn.edu Source of funding: National Institute of Mental Health, National Alliance for research in Schizophrenia and Affective Disorders, and the Mental Illness and Neuroscience Discovery Institute. c Additional references are published online only at http://ebmh.bmj.com/content/ vol11/issue3 C O M M EN TA R Y K umra and colleagues have offered a timely review on the efficacy and tolerability of second-generation antipsychotics (SGAs) for the treatment of Early Onset Schizophrenia Spectrum (EOSS) disorders. This review potentially helps clinicians analyse and critically interpret the available study results relevant to EOSS disorders. A relatively well-supported conclusion that clozapine offers superior efficacy for treatment of EOSS is offered. However, it is difficult to draw firm conclusions regarding comparative efficacy for other SGAs given the lack of differences in efficacy noted in the existing literature. Therefore, the distinction between individual medications is likely to be based on differences in adverse event profiles, an important principle for the practicing clinician. The authors allude to this issue, but readers are left to decide for themselves whether this might be the primary basis for choosing between agents. There are limited head-to-head comparisons of SGAs addressing relative risk of adverse events in children and adolescents. Having noted this limitation, the authors summarise that first generation antipsychotics probably have a higher risk of extrapyramidal side-effects (EPS) and that certain medications like olanzapine and clozapine probably have a higher risk of metabolic side-effects like weight gain, consistent with evidence from adults. The authors also note that the adverse event ‘‘stakes’’ are higher for children than adults due to the length of exposure and/or the longer opportunity to develop gradual onset, weight-related conditions like diabetes mellitus or cardiovascular disease. A brief summary of methods to avoid or attenuate antipsychotic-associated weight gain is provided, including lifestyle interventions and adjunctive pharmacotherapies such as metformin or sibutramine, although neither drug therapy has been adequately tested or approved for this use in children. However, the differential risk of weight gain rationally suggests the preferential first-line use of lower-risk medications, which is not clearly stated by the authors. These fundamentally different approaches are of great interest to clinicians and might ideally deserve equal and thorough treatment in future studies and reviews. Despite these limitations, this review offers a succinct compilation of what is known about the efficacy and risk profile of antipsychotics in EOSS disorders, usefully highlighting crucial areas where future studies on the treatment of these complex and disabling disorders are needed. Ginger Nicol, MD, John Newcomer, MD Washington University School of Medicine, Department of Psychiatry, St Louis, USA Competing interests: None. Therapeutics EBMH August 2008 Vol 11 No 3 81