Treatment-related weight gain and metabolic complications in children with mental health disorders: Potential role for lifestyle interventions Alejandra M. Wiedeman, PhD Postdoctoral Fellow | Devlin Lab - ule Bc 27 A ; _ | Children’s Canadian Nutrition Society Hospital January 12‘, 2021 Research InstituteMENTAL HEALTH DISORDERS IN CHILDREN @QXO LO LO Over 1 million children are estimated to have a mental health disorder in Canada Prevalence across provinces varies (11-17%) In BC, 14% of children experience a mental health disorder before the age of 19 years In BC, this is equal to 1 in 7 children Public Health Agency of Canada. 2015 Mental Health Commission of Canada. 2013MENTAL HEALTH DISORDERS IN CHILDREN Mental Health Disorders Anxiety disorders Depressive disorder Attention deficit hyperactivity disorder Mood disorders Psychotic disorders Pervasive developmental disorder Adjustment disorders Second-generation antipsychotics (SGAs) 10 20 Percentage of children Primary psychiatry diagnosis in children (n=506) at BC Children’s Hospital Canadian Mental Health Association. 2014 Wiedeman et al. 2020 manuscript in preparation Lambert et al. Can Fam Physician, 20: Lee et al. J Child Adolesc Psychopharmacol. 2018}SECOND-GENERATION ANTIPSYCHOTICS (SGAs) Atypical antipsychotics Treatment of schizophrenia, bipolar disorder, irritability/aggression Used off-label to treat a range of mental health disorders In BC, 18-fold increase in SGAs prescription rates for children since 1996 Patients per 1000 population 96/97 98/99 00/01 02/03 04/05 06/07 08/09 10/11 Fiscal year (1996-2011) Trends in antipsychotic prescriptions to children in BC Sohn et al. Medicine. 2016;95:e3; Olfson et al. N Engl J Med. 2015;372:2029-38 Ronsley et al. Can J Psychiatry. 2013;58:361-9 Chen et al. Clin Drug Investig. 2018; 38:449-55SECOND-GENERATION ANTIPSYCHOTICS (SGAs) c © 2 = Oo So £ oO £ <= oO no x Risperidone Quetiapine Aripiprazole Olanzapine Ziprasidone Paliperidone Lurasidone Clozapine Second-generation antipsychotics used to treat children (n=230) at BC Children’s Hospital Wiedeman et al. App! Physiol Nutr Metab. 2020; Nov 23 onlineSECOND-GENERATION ANTIPSYCHOTICS (SGAs)Differentiate the metabolic complications in children with mental health disorders treated with second-generation antipsychoticsSGAsS — METABOLIC COMPLICATIONS Increased Excessive weight blood pressure gain and Obesity Dyslipidemia Elevated fasting glucose and insulin Greater risk of \ Y type 2 diabetes Allison et al. Am J Psychiatry. 1999) Panagiotopoulos et al. Can J Psychiatry. 2009;STUDIES ASSESSING WEIGHT GAIN AND OBESITY Almandil et al 2013 Meta-analysis of 21 double-blind RCT Children (n=2455) treated with risperidone, aripiprazole, and olanzapine Weight gain, SGA-treated vs placebo: + olanzapine 3.5 kg + risperidone 1.8 kg, and + aripiprazole 0.9 kg Vandenderghe et al 2018 Retrospective chart review Children starting SGA treatment (n=42) Follow-up at 1 and 3-month A weight gain >4% after 1 month was the best predictor for a weight gain >15% after 3 months Nicol et al 2018 Prospective RCT Children starting SGA treatment (n=144), randomized to olanzapine, risperidone or aripiprazole 12 weeks of treatment Total body fat (DEXA): + olanzapine 4.1%, + risperidone 1.2%, and + Aripiprazole 1.7%STUDIES ASSESSING METABOLIC COMPLICATIONS Galling et al 2016 Meta-analysis of 13 longitudinal studies Children SGA treatment (n=185105), healthy controls (n=298803), and psychiatric controls (n=1342121) Mean follow-up 1.7 years t Type 2 diabetes risk SGA-treated vs: + Healthy controls, RR=3.02 + Psychiatric controls, RR= 1.79 llies et al 2017 Retrospective chart review Children starting SGA treatment (n=32) Follow-up 24 months + 7 Fasting glucose 0.29 mmol/L + Hyperglycemia (5.6-6.9 mmol/L) 9% + Type 2 diabetes (7 mmol/L) 3% Nicol et al 2018 Prospective RCT Children starting SGA treatment (n=144), Randomized to olanzapine, risperidone or aripiprazole 12 weeks of treatment Insulin sensitivity (hyperinsulinemic. clamp) + | aripiprazole 29%, + | olanzapine 30%, and + risperidone 2.3%SGAsS — METABOLIC COMPLICATIONS I SGA-Treated (n=230) EI SGA-Naive (n=377) m= General pediatric population c 2 Zn 5s 52 oD Oc Ss £2 se 2 o ao Overweight Elevated waist Elevated BP Low HDL- Elevated Impaired and obesity circumference _ @120/800r cholesterol __triglycerides_ fasting glucose (BMI285" percentile) (290 percentile) 290" percentile) (<1.93 mmol/L) (21.47 mmol/L) (25.6 mmol/L) Prevalence of metabolic complications in SGA-treated and SGA-naive children at BC Children’s Hospital Median treatment duration 6 months. * P < 0.05 Ng et al. Lancet. 2014;384:766-81 Wiedeman et al. App! Physio! Nutr Metab. 2020; Nov 23 onlineDiscuss the dietary intakes and physical activity data from children with mental health disordersSGAsS — DIETARY ENERGY INTAKES SGA treatment may cause hyperphagia Hypothalamus Conflicting and inconclusive appetite/satiety So regulation findings Most studies have been conducted in adults with schizophrenia Many have assessed SGAs not commonly used in children (olanzapine) Pancreas Cuerda et al. Eur J Clin Nutr. 2014;68:146-52 Ballon et al. Trends Endocrinol Metab. 2014;25:593-600STUDIES ASSESSING ENERGY INTAKE AND APPETITE Gothelf et al 2002 Longitudinal Male youth with schizophrenia treated with olanzapine (n=10) 4 weeks of treatment Baseline vs 4 weeks, + 4 Dietary total energy intakes (2-day weighted food records) * mean increase 589 kcal/d (2127 + 1032 kcal/d vs 2716 + 958 kcal/d) Ngai et al 2018 Oral glucose tolerance test Children SGA treated, risperidone (n=20), quetiapine (n=16), and SGA-naive (n=18) Risperidone vs SGA-naive: + 1 Appetite (visual analogue scale) No difference in satiety hormones Barker et al 2018 Cross-sectional Children SGA-treated (n=35) and SGA-naive (n=29) + Dietary total energy intakes (3-day food records) were not different + SGA-treated 1971 + 649 kcal/d and SGA-naive 1734 + 486 kcal/d childrenSGAs — DIETARY ENERGY AND NUTRIENT INTAKES + 237 kcal/d Di SGA-Treated Dl SGANaive k 2 @ 6.3 8 (within group) Percentage of Children 8 = g o x £ = > > oO c Ww 0. ° SGA-Treated SGA-Naive Total Fat Saturated Fat Sugar Sodium >35% energy >7% energy >20% energy >2300 mg/d Dietary intakes in SGA-treated (n=35) and SGA-naive children (n=29) Unadjusted mean + SD. P-value = NS Barker et al. Clin Nutr ESPEN. 2018;23:205-11PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOUR Guidelines (5-17 years) I Psychiatric (n=100) . not BD School (n=110) Physical Activity fm Screen time guideline + Moderate to vigorous > 260 min/d + Muscle/bone strengthening > 23 d/wk Time (hours) CHMS ‘37.6% 57 min/d Sedentary Behaviour Total Screen Television Gaming Non- Time gaming + Limit sitting for extended periods Amount of time spent on different electronic media in youth CHMS y 28.5% 4.2 h/d * P< 0.05, after controlling for SES and sex Public Health Agency of Canada. 2017 Baer et al. Can J Psychiatry. 2012;57:728-35 CHMS Canadian Health Measures Survey (2014-2015) ‘Tremblay et al. App/ Physiol Nutr Metab. 2016;41:S311-27 + Recreational screen time > <2 h/dGothelf et al 2002 Longitudinal Male youth with schizophrenia treated with olanzapine (n=10) 4 weeks of treatment At baseline and after 4 weeks: + NS change in physical activity (accelerometer) + 4.4 vs 2.9 %time moderate to vigorous Cuerda et al 2011 Longitudinal Youth starting SGA treatment (n=16) Baseline during hospitalization Follow-up 12 months Baseline vs 12 months: +t Energy expenditure (self-reported physical activity using a 3-day record) + 2010 + 357 vs 2688 + 472 kcal/d Cote et al 2014 Cross- sectional Children SGA-treated (n=166) and SGA-naive (n=220) SGA-treated children who met the physical activity recommendation (260 min) vs who did not: + | Insulin resistance (HOMA-IR) + | BMIz-scoresUnderstand the potential role of lifestyle interventions on metabolic complications in children with mental health disordersLIFESTYLE INTERVENTIONS IN CHILDREN Curtis et al 2016 EU CE UM Cau Cel) Youth/young adults (14-25 y) with first-episode psychosis + Individualized intervention (n=16; nurse, dietician, exercise physiologist, and youth peer wellness coaches + standard care) + Standard care (n=12) Mean change after 12 weeks, Intervention vs standard care: + | Weight gain + | Waist circumference NS effect on blood glucose and lipids Intervention: + | Energy intake + ¢ Physical activity Correll et al 2020 Children with mental health disorders and overweight/obesity + Healthy lifestyle education + pharmacological modifications (n=80) + Healthy lifestyle education (n=47) Mean change after 24 weeks, Education + Pharmacological vs Education: + | BMI z-scores + | HbAtc + NS effect on blood lipidsLIFESTYLE INTERVENTIONS IN CHILDREN HUD NS Current follow-up practices often fail to detect metabolic and neurological adverse reactions in children treated with second- generation antipsychotics ‘irs Kako, Leena Pilakosl Pal Keskinen, Ral Saimelin, Kaja Pura Enhancing metabolic monitoring for children and adolescents using second-generation antipsychotics Mary Coughlin RN, MSCN&@, Catherine L. Goldie RN, Ph, Deborah Tregunno RN, PhD, Joan Tranmer RN, Pho, xanellos Sutton RN, BSCN, PHC-NP, Sarosh Khalid-Khan MD, DABPN Eanes Health Information Preference among Youth and Caregivers related to Second-Generation Antipsychotic Treatment Yan Xu, BSe!2; Duc Nguyen, MD, PhD*; Jana Davidson, MD, FRCPC; Constadina Panagiotopoulos, MD, FRCPC® Kakko et al. Acta Paediatr. 2020;109:342-8 Coughlin et al. Can J Psychiatry. 2018;63:240-49 Xu et al. J Can Acad Child Adolesc Psychiatry. 2012:21;302-9BC PROVINCIAL MENTAL HEALTH METABOLIC PROGRAM What is Specialized care to children and youth at risk for or are experiencing obesity and metabolic side effects associated with the use of psychotropics Rear The multi-disciplinary team includes: + Pediatric Endocrinologist + Occupational Therapist + Nurse Practitioner + Child & Adolescent Psychiatrist + Dietitian Healthy living toolkits for professionals and families* (*English, French, Farsi, Punjabi, Korean, Traditional Chinese, and Simplified Chinese) Modules include: + Healthy Eating + Healthy Sleep Habits Being Active Together + Managing Stress https://keltymentalhealth.ca/toolkits http://www. bechildrens.ca/health-professionals/clinical-resources/mental-health/metabolic-complicationsUae Children are increasingly being treated with second-generation antipsychotics for mental health disorders Dietary and physical activity assessments are not commonly considered in clinical settings Randomized controlled trials of lifestyle interventions are needed to determine the effectiveness of mitigating the cardiometabolic complications in second-generation antipsychotic-treated childrenACKNOWLEDGEMENTS: Devlin & Panagiotopoulos Labs Dr. Tiffany Ngai Amanda Henderson Ricky Thandi Dew 11a Narr Tel ig - Cynthia Ramirez | = a EMM 1- — Dr. Nicha Boonpattrawong v BC. BC MENTAL HEALTH Children's ‘SUBSTANCE USE SERVICES Hospital D BC DIABETES