Monitoring of metabolic adverse events of second-generation antipsychotics in a naive paediatric population followed in mental health outpatient and inpatient clinical settings: MEMAS prospective study protocol.

INTRODUCTION: Second-generation antipsychotics (SGAs) are widely used in the paediatric population. It is currently established that SGAs may induce metabolic adverse events (AEs) such as weight gain, perturbation of blood lipids or glucose with risk of potential cardiovascular morbidity and mortality. The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in children (CAMESA) has published recommendations for monitoring the metabolic AEs of SGAs. Factors that may be associated with the onset of SGA's metabolic AEs and long-term consequences are less studied in the literature. The objectives of our research are to evaluate some factors that can influence the development of the SGA's metabolic AEs and to study clinical adherence to CAMESA guidelines. METHODS AND ANALYSIS: The Monitoring des Effets Métaboliques des Antipsychotiques de Seconde Génération study is a multicenter, prospective, longitudinal observational study with repeated measures of metabolic monitoring over 24 months. Two recruiting centres have been selected for patients under 18 years of age, previously naive of antipsychotics, starting an SGA or who have started an SGA for less than 4 weeks regardless of the diagnosis that motivated the prescription. Assessments are performed for anthropometric measures, blood pressure, blood tests at baseline and 1, 2, 3, 6, 9, 12 and 24 months of follow-up. ETHICS AND DISSEMINATION: The study protocol was approved by the CHU Sainte-Justine's Research Ethics Board (MP-21-2016-1201) in 2016 and obtained institutional suitability for the 'Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal' Research Center in May 2018. For all participants, written consent will be obtained from parents/caregivers as well as the participant's assent in order to enable their participation in this research project. The results of this research will be published. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (number NCT04395326).

Long-Term Metabolic Monitoring of Youths Treated with Second-Generation Antipsychotics 5 Years after Publication of the CAMESA Guidelines Are We Making Progress? Surveillance Métabolique à Long Terme des Jeunes Traités par Antipsychotiques de Deuxième Génération, Cinq ans Après la publication des Lignes Directrices Camesa: Faisons-Nous des Progrès?

OBJECTIVE: The potential metabolic adverse effects of second-generation antipsychotics (SGA) need to be monitored. The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics (CAMESA) offers guidelines for this purpose. We aimed to evaluate the long-term rates of youths receiving monitoring in mental health clinics and document the factors that may influence them. METHOD: The charts of 180 patients (13.3 ± 3.1 years, 54.4% males) receiving SGA treatment for the first time between January 2016 and June 2018 were reviewed. Monitoring was divided into baseline and 1- to 6-month and 9- to 24-month periods. Population under study was stratified into children (4 to 12 years) and adolescents (13 to 18 years). Sociodemographic characteristics, psychiatric diagnosis and comorbidities, prescribed SGAs and comedications, anthropometric measures (AM), blood pressure (BP), blood tests (BT), electrocardiogram, and the psychiatrist's years of practice were collected. Cross tables were used to present the monitoring rates. Categories were compared by covariate analysis. Rates of patients monitored across categories were compared using Fisher exact test. RESULTS: Monitoring rates for AM, BT, and BP were 55%, 47.8%, and 46.7% at baseline; 50%, 41.7%, and 45.2% at 1 to 6 months; and 47.2%, 41.5%, and 40.6% at 9 to 24 months, respectively. Higher monitoring rates were significantly associated with adolescent status (baseline, 1 to 6 months), a diagnosis of psychotic and/or affective disorder (baseline, 1 to 6 months, 9 to 24 months), having ≤1 psychiatric comorbidities (1 to 6 months), high SGA dose (baseline, 1 to 6 months), and clinician's experience (baseline, 9 to 24 months). Significantly lower monitoring rates were associated with the psychostimulant/atomoxetine comedication (baseline, 1 to 6 months, 9 to 24 months). CONCLUSION: Five years after publication of the CAMESA guidelines, metabolic monitoring is conducted for less than half of patients. In our sample, age, diagnostic category, psychiatric comorbidities, SGA dose, clinician's experience, and comedications influenced the monitoring rates. Major progress still needs to be made before reaching a satisfactory level of monitoring.

Impact of Psychoactive Drug Use on Developing Obesity among Children and Adolescents with Autism Spectrum Diagnosis: A Nested Case-Control Study.

BACKGROUND: Obesity in children on the autism spectrum (AS) is becoming a significant health concern. The purpose of this study was to identify the predictors of obesity in a cohort of AS youth and to assess the impact of psychoactive medication use while exploring the second-generation antipsychotics (SGAs) dose-response curve. STUDY DESIGN: A nested case-control study was conducted using Quebec public administrative databases. Subjects with AS <18 years [≥2 diagnoses International Classification of Diseases: 9th revision (ICD-9): 299.X] were identified (January 1993 to May 2011). Cases were defined as subjects with an obesity diagnosis (ICD-9: 278.X) during the coverage period and matched to 10 controls for age, gender, and follow-up duration. Potential risk factors for obesity (sociodemographic characteristics, other neuropsychiatric conditions, and psychoactive drug use) were evaluated and analyzed using conditional logistic regression. RESULTS: From a cohort of 5369 AS subjects, we identified 135 obesity cases. Among the different risk factors, only SGAs [rate ratio (RR): 1.04, 95% confidence interval (CI): 1.01-1.07] increased the probability of obesity in multivariate analysis. Exposure for ≥12 months increased significantly the likelihood of obesity (RR: 2.01, 95% CI: 1.18-3.42). Higher risk was observed with chlorpromazine-equivalent daily doses ≥100 mg (RR: 2.20, 95% CI: 1.00-4.84). Among SGA users, concomitant antidepressants (per 30-day exposure) slightly increased the probability (RR: 1.08, 95% CI: 1.01-1.15). CONCLUSIONS: Longer and higher SGA exposure increased the risk of obesity, which has to be considered in relation to the paucity of evidence supporting long-term psychoactive medication use in AS children. Results highlight the need to promote optimal use and interventions to mitigate metabolic side effects of SGAs in this population.

Long-Term Metabolic Effects in French-Canadian Children and Adolescents Treated with Second-Generation Antipsychotics in Monotherapy or Polytherapy: A 24-Month Descriptive Retrospective Study.

OBJECTIVE: To compare weight and glucose changes of long-term second-generation antipsychotic (SGA) monotherapy versus polytherapy (switching or combining SGAs) in children and adolescents. METHODS: This is a 24-month retrospective study conducted between November 2005 and June 2013. From 147 antipsychotic-naive patients selected (mean age, 12.8 years; 95% confidence interval [CI], 9.8-15.9), 116 (78.9%) received SGA monotherapy and 31 (21.1%) SGA polytherapy for up to 24 months. Height, weight, and fasting glucose (FG) were measured at baseline and 1, 3, 6, 12, and 24 months. Linear mixed-model analysis was used to compare weight, body mass index z score (BMI z score), and glucose changes between the 2 SGA treatment groups, with the repeated factor being the time relative to baseline at 1, 3, 6, 12, and 24 months. RESULTS: Overall, after 24 months of SGA treatment, mean weight increased significantly by 12.8 kg (95% CI, 10.4-15.0), BMI z score by 0.44 (95% CI, 0.21-0.68), and FG levels by 0.29 mmol/L (95% CI, 0.11-0.47). Incidence of overweight/obesity was 22.6%, BMI z score increase over 0.5 was 9.4%, impaired fasting glucose was 9.4%, and type 2 diabetes mellitus was 3.1%. Regarding metabolic effects, no significant difference was found between the subjects taking a single SGA and those exposed to an SGA polytherapy. CONCLUSION: Our study confirms the significant increase of metabolic complications during 24 months of SGA treatment without excluding or confirming a difference between the 2 groups of treatment (mono vs. poly).