Jana Davidson

Increased Prevalence of Obesity and Glucose Intolerance in Youth Treated with Second—Generation Antipsychotic Medications

Objective: To compare the rates of obesity, impaired fasting glucose (IFG), and type 2 diabetes between second-generation antipsychotic (SGA)-treated and -naive youth. Methods: A retrospective chart review was conducted for all child and adolescent psychiatry emergency admissions over 2.5 years. Data collected included age, sex, psychiatric diagnosis, medications, height, weight, fasting glucose, and lipid profile. Body mass index (BMI) was standardized for age and sex and converted to a z score. Overweight was defined as a BMI between the 85th and 95th percentile and obese as a BMI at the 95th percentile or greater for age and sex. The 2007 American Diabetes Association criteria for IFG and type 2 diabetes were used. Results: Among the 432 admissions, 167 (39%) had both height and weight measured, and 145 (34%) had fasting glucose measured. The mean zBMI was higher in the SGA-treated (n = 68), compared with the SGA-naive group (n = 99) (mean difference 0.81; 95% CI 0.46 to 1.16). In the SGA-treated group, 31% were obese and 26% were overweight, compared with 15% and 8%, respectively, in the SGA-naive group (P < 0.01). In the SGA-treated group (n = 65), 21.5% had IFG or type 2 diabetes, compared with 7.5% in the SGA-naive group (n = 80) (P = 0.01). Conclusions: Youth treated with SGAs have significantly higher rates of obesity and glucose intolerance than SGA-naive youth. These data emphasize the need for consistent metabolic monitoring of youth with psychiatric disorders who are prescribed SGAs.

A population-based study of antipsychotic prescription trends in children and adolescents in British Columbia, from 1996 to 2011.

Objectives: To establish prevalence rates of antipsychotic (AP) prescriptions for children 18 years of age or younger in British Columbia (BC) from 1996 to 2011 by age, sex, AP type, and primary diagnosis; and to identify the predominant AP prescribers for children by specialty training. Methods: BC Ministry of Health administrative data were used to describe AP prescriptions for youth aged 18 years or younger. Comparisons were made using population prevalence based on sex; age group; AP; International Classification of Diseases, Ninth Revision, diagnosis; and prescriber specialty. Results: From 1996 to 2011, overall AP (both first and second generation) prescription prevalence rate increased 3.8-fold (1.66 to 6.37 per 1000 population); second-generation AP (SGA) prescriptions increased 18.1-fold (0.33 to 5.98 per 1000 population). The highest increase in all AP prescriptions occurred in males aged 13 to 18 years (3.3 to 14.4 per 1000 population; 4.4-fold), followed by similar increases in males aged 6 to 12 years (2.3 to 8.6 per 1000 population; 3.7-fold) and in females aged 13 to 18 years (2.8 to 10.7 per 1000 population; 3.8-fold). Overall, the 3 most common diagnoses associated with all AP prescriptions were depressive disorders (12.8%), hyperkinetic syndrome of childhood (11.7%), and neurotic disorders (11.1%); however, variation was observed by prescriber specialty training. Among all new AP prescriptions in 2010/11, 38.6%, 34.3%, and 15.6% were provided by psychiatrists, family physicians, and pediatricians, respectively. Conclusions: There has been an exponential rise in SGA prescriptions in BC secondary to extensive off-label use, not only by psychiatrists but also by family physicians and pediatricians. Knowledge translation initiatives promoting evidence-based prescribing and monitoring practices related to SGA treatment need to target all 3 prescriber groups and be tailored for age subgroups.

A Naturalistic Study of Predictors and Risks of Atypical Antipsychotic Use in an Attention-Deficit/Hyperactivity Disorder Clinic

OBJECTIVE This was an exploratory study to examine the use of atypical antipsychotics in an attention-deficit/hyperactivity disorder (ADHD) clinic. METHOD A total of 194 patients was examined to compare those receiving atypical or second-generation antipsychotics (atypicals) from those who were not. A sample of 27 children on atypicals received laboratory investigation for indicators of possible metabolic effects. RESULTS In all, 19.1% of the patients in the clinic were receiving atypicals with a mean duration of 313 days; 36 of 37 patients on atypicals had received risperidone, with a mean dose of 0.62 mg. Children receiving atypicals were statistically more likely to have a severe co-morbid disorder, a lower Childrens Global Assessment Scale score, a greater total score on the teacher Strengths and Difficulties Questionnaire, and greater difficulty with parent-rated symptoms of being touchy, worried, rages, and explosive outbursts. There were no differences found in measures of functioning, adaptive skills, quality of life, or ADHD symptoms. In the subset of children studied for potential metabolic effects, 68.0% had a waist circumference > or =90(th) percentile that was independent of weight gain, 18.5% had impaired fasting glucose, 12.5% had elevated blood pressure, 11.1% had elevated triglycerides, and 16.7% met full criteria for metabolic syndrome. CONCLUSION Clinical implementation of the efficacy studies of risperidone for disruptive behavior disorders has led to a significant change in practice. Almost 1 in 5 patients are now receiving atypical neuroleptics, typically to treat severe co-morbid disorders and symptoms other than ADHD per se. Despite these children receiving low doses, concomitant stimulants, and low body mass index z-scores, a significant proportion of children demonstrated either one or more components or the full criteria for metabolic syndrome.

Waist Circumference Is a Sensitive Screening Tool for Assessment of Metabolic Syndrome Risk in Children Treated with Second-Generation Antipsychotics

Objective: To compare the prevalence of metabolic syndrome (MetS) and its components in second-generation antipsychotic (SGA)-treated and SGA-naive children; and to explore the utility of clinical markers, such as waist circumference (WC) and body mass index (BMI), as screening tools for MetS. Methods: Subjects were prospectively recruited from the Psychiatry Emergency Unit at British Columbia Childrens Hospital. As part of a quality-assurance project, a metabolic monitoring protocol was implemented, including collection of anthropomorphic and laboratory data. Results: From January 2008 to February 2010, there were 117 SGA-treated and 217 SGA-naive children recruited. The overall prevalence of MetS was 19.0% (16/84; median treatment duration = 14 months) in SGA-treated and 0.8% (1/127) in SGA-naive children (OR 29.7; 95% CI 3.85 to 228.40, P < 0.001), with an increased prevalence of all components except high-density lipoprotein cholesterol (HDL-C), respectively: elevated WC (40.7% and 10.1%; P < 0.001); hypertriglyceridemia (33.7% and 18.8%; P = 0.01); impaired fasting glucose (12.5% and 0.7%; P = 0.005); and elevated blood pressure (41.2% and 16.5%; P < 0.001). SGA treatment was the strongest predictor of MetS (OR 19.2; 95% CI 2.30 to 160.44, P = 0.006) followed by male sex (OR 5.7; 95% CI 1.08 to 30.62, P = 0.04). Presence of abdominal obesity was more sensitive (92.9%) than BMI (68.8%), while fasting glucose of 5.6 mmol/L or more and HDL-C of 1.03mmol/L or less were most specific (94.1%) in correctly identifying MetS. Conclusions: SGA treatment confers a significantly increased risk for MetS over the long term. WC measurement is a simple and sensitive screening tool for determining MetS risk in SGA-treated children. These data highlight the dangers of SGA treatment and the importance of standardized metabolic monitoring using sex- and age-adjusted tables in this population.

Increased Risk of Obesity and Metabolic Dysregulation Following 12 Months of Second-Generation Antipsychotic Treatment in Children: A Prospective Cohort Study

Objective: To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine. Methods: This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis. Results: After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively. Conclusion: Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

Metabolic monitoring training program implementation in the community setting was associated with improved monitoring in second-generation antipsychotic-treated children.

Objective: To determine whether implementation of a metabolic monitoring training program (MMTP) in an urban community-based setting improved monitoring in children treated with second-generation antipsychotics (SGAs) and changed prescription rates of SGAs to children. Method: The MMTP was implemented in the Vancouver Coastal Health Child and Youth Mental Health Teams (CYMHTs) on January 1, 2009. A retrospective review of paper charts and electronic records for children seen at the CYMHTs from September 1, 2007, to May 1, 2010, was performed to collect the following data: age, sex, foster care, immigrant status, Axis I diagnosis, and medications. In SGA-treated children, anthropometric measurements and blood work completed at baseline and 3, 6, and 12 months were also collected. Results: Among the 1114 children seen pre-MMTP and 1262 children seen post-MMTP implementation, 174 (15.4%) and 81 (6.4%), respectively, were SGA-treated (P < 0.001). Among the SGA-treated children seen at the CYMHTs after MMTP implementation, 38.3% had a copy of the MMTP in their paper chart. Metabolic monitoring increased by up to 40% at baseline (P < 0.01), 20% at 3 (P < 0.01) and 6 months (P < 0.01), and 18% at 12 months after MMTP implementation. Conclusions: Implementation of an MMTP was associated with significantly improved monitoring rates of anthropometric and blood work parameters at baseline and the 3- and 6-month time points, with a trend for improvement at the 12-month time point, in SGA-treated children cared for in urban community mental health clinics. In addition, a 56% decrease in SGA prescriptions was observed following MMTP implementation in this population.

Quetiapine treatment in youth is associated with decreased insulin secretion.

Abstract Second-generation antipsychotics (SGAs) are commonly prescribed to youth but are associated with metabolic effects including obesity and diabetes. The mechanisms underlying diabetes development are unclear. The purpose of this study was to compare glucose homeostasis, insulin sensitivity, insulin secretion, and overall &bgr;-cell function in risperidone-treated, quetiapine-treated, and SGA-naive youth with mental illness. We conducted a cross-sectional study in which youth aged 9 to 18 years underwent a 2-hour oral glucose tolerance test. Indices for insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), and &bgr;-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) were calculated. A total of 18 SGA-naive, 20 risperidone-treated, and 16 quetiapine-treated youth participated. The 3 groups were similar in age, sex, ethnicity, body mass index standardized for age and sex, pubertal status, degree of psychiatric illness, psychiatric diagnoses, and other medications. The median treatment duration was 17 months (range, 3–91 months) for risperidone-treated youth and 10 months (range, 3–44 months) for quetiapine-treated youth. The quetiapine-treated group had lower insulinogenic index (P < 0.01) and lower ISSI-2 (P < 0.01) compared with that in the SGA-naive group. Only the body mass index standardized for age and sex was negatively associated with Matsuda index (&bgr; = −0.540, P < 0.001) in all youth. Quetiapine treatment was negatively associated with insulinogenic index (&bgr; = −0.426, P = 0.007) and ISSI-2 (&bgr; = −0.433, P = 0.008). Quetiapine reduced the insulin expression in isolated mouse islets suggesting a direct &bgr;-cell effect. Our results suggest that quetiapine treatment in youth is associated with impaired &bgr;-cell function, specifically lower insulin secretion. Prospective longitudinal studies are required to understand the progression of &bgr;-cell dysfunction after quetiapine initiation.

What are Effective Strategies for Implementing Trauma-Informed Care in Youth Inpatient Psychiatric and Residential Treatment Settings? A Realist Systematic Review

BackgroundMany young people who receive psychiatric care in inpatient or residential settings in North America have experienced various forms of emotional trauma. Moreover, these settings can exacerbate trauma sequelae. Common practices, such as seclusion and restraint, put young people at risk of retraumatization, development of comorbid psychopathology, injury, and even death. In response, psychiatric and residential facilities have embraced trauma-informed care (TIC), an organizational change strategy which aligns service delivery with treatment principles and discrete interventions designed to reduce rates of retraumatization through responsive and non-coercive staff-client interactions. After more than two decades, a number of TIC frameworks and approaches have shown favorable results. Largely unexamined, however, are the features that lead to successful implementation of TIC, especially in child and adolescent inpatient psychiatric and residential settings.MethodsUsing methods proposed by Pawson et al. (J Health Serv Res Policy 10:21–34, 2005), we conducted a modified five-stage realist systematic review of peer-reviewed TIC literature. We rigorously searched ten electronic databases for peer reviewed publications appearing between 2000 and 2015 linking terms “trauma-informed” and “child*” or “youth,” plus “inpatient” or “residential” plus “psych*” or “mental.” After screening 693 unique abstracts, we selected 13 articles which described TIC interventions in youth psychiatric or residential settings. We designed a theoretically-based evaluative framework using the active implementation cycles of the National Implementation Research Network (NIRN) to discern which foci were associated with effective TIC implementation. Excluded were statewide mental health initiatives and TIC implementations in outpatient mental health, child welfare, and education settings. Interventions examined included: Attachment, Self-Regulation, and Competency Framework; Six Core Strategies; Collaborative Problem Solving; Sanctuary Model; Risking Connection; and the Fairy Tale Model.ResultsFive factors were instrumental in implementing trauma informed care across a spectrum of initiatives: senior leadership commitment, sufficient staff support, amplifying the voices of patients and families, aligning policy and programming with trauma informed principles, and using data to help motivate change.ConclusionsReduction or elimination of coercive measures may be achieved by explicitly targeting specific coercive measures or by implementing broader therapeutic models. Additional research is needed to evaluate the efficacy of both approaches.

Ensuring the Safety of Children Treated with Second-Generation Antipsychotics

Second-generation antipsychotic (SGA) prescriptions for children have steadily increased over the past two decades. This is in part due to the perception of a reduction in neurological side effects with SGAs as compared to first-generation antipsychotics. However, the current literature shows that children treated with SGAs are at risk for metabolic side effects including central obesity, impaired glucose tolerance, hypertension, dyslipidemia, and metabolic syndrome. To ensure the safety of children treated with SGAs, it is important that (1) these medications are used for evidence-based indications only; (2) prescribing physicians monitor metabolic changes at regular time intervals per the current recommendations; and (3) metabolic complications are identified early and treated through promotion of a healthy lifestyle, use of the lowest effective dose of the SGA, and reduction in the use of multiple medications.