Antipsychotic-Related Risk for Weight Gain and Metabolic Abnormalities During Development Christoph U. Correll, MD
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1 Antipsychotic-Related Risk for Weight Gain and Metabolic Abnormalities During Development Christoph U. Correll, MD Professor of Psychiatry and Molecular Medicine Hofstra North Shore - LIJ School of Medicine Medical Director Recognition and Prevention Program The Zucker Hillside Hospital New York, USA
2 Disclosures: Christoph U. Correll, MD I have an interest in relation with one or more organizations that could be perceived as a possible conflict of interest in the context of this presentation. The relationships are summarized below: Interest Grants Shares Honoraria and Advisory Boards Name of the Organization Bristol-Myers Squibb, Feinstein Institute for Medical Research, Janssen/Johnson & Johnson, National Institute of Mental Health (NIMH), Otsuka, Takeda, Thrasher Foundation None AbbVie, Alkermes, Bristol-Myers Squibb, Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Reviva, Roche, Sunovion, Supernus, and Takeda.
3 Overview Mental Disorders And Physical Health Mechanisms Antipsychotic Effects Conclusions
4 Mental Disorders and Physical Health
5 2010: Years Lived with Disability MALES FEMALES Vos T et al. Lancet 2012; 380:
6 2010: Disability Adjusted Life Years (DALYs) MALES FEMALES DALYs= Years of Life Lost + Years Lived with Disability Murray C et al. Lancet 2012; 380:
7 Trajectories
8 Early Cardiometabolic Risk Indicator Differentiation In Adults with Psychosis From the General Population Foley D et al. PLoS One Dec 18;8(12):e82606.
9 Hazard Ratios for Risk of DM and CHD By BMI in Adolescence and Adulthood in 37,674 Israeli Men BMI increase: 0.3/year and 15 kg or 4.0 until endpoint Tirosh A. et al. N Engl J Med 2011;364:
10 Antipsychotic Effects
11 Atypical Antipsychotic Use Increasing Dramatically in Youth : Olfson M et al. Arch Gen Psychiatry Jun;63:679-85; Aparasu R & Bhatara V. Curr Med Res Opin Jan;23(1):49-56; Olfson M et al. Arch Gen Psychiatry Dec;69(12): : ~10% of mental health visits involved SGA treatment : 31% of psychiatrists visits involved antipsychotic treatment : DBDs most common diagnoses in child 63% and adolescent (34%) visits
12 2010: Antipsychotic Use in the US by Age and Sex Olfson M et al. JAMA Psychiatry in press.
13 US Trends in Youth s Reporting Severe Mental Health Impairment* and Outpatient Mental Health Service Use Rated by Columbia Impairment Scale (CIS) cut scores; Medical Expenditure Panel Surveys (ages 6-17 years): N=15,307 ( ), N=19,450 ( ), N=18,865 ( ). Olfson M et al. NEJM in press.
14 Main Effect, Mediator and Moderator Model of Antipsychotic Induced Weight Gain Moderators Genetic effects Demographics, setting and illness Drug effects Baseline antipsychotics and co-medications Dose (mg/dl) Changes in neurotransmitters, peptides and hormones regulating appetite and energy homeostasis Baseline diet Baseline BMI Baseline activity Antipsychoticinduced weight change Mediators Dietary changes Activity changes Co-medications Adverse effects Correll CU et al. Trends Mol Med Feb;17(2):97-107
15 12-week Cardiometabolic Effects of SGAs in AP-Naïve Youth Body Weight Fasting Total Cholesterol Fasting Glucose Fasting Triglycerides * Correll CU et al. JAMA 2009;302:
16 Weight Gain > 7% 12-week Weight Gain > 7% (N=541) 100 p=.037 p=.014 p=.015 p< OLZ RIS ZPD QTP APZ AP-Naïve AP-History AP-Switch Correll et al., unpublished data and Correll CU et al. JAMA 2009;302(16):
17 Number needed to harm (NNH) for adverse body composition outcomes Antipsychotic-naïve sample. Total n=272* Outcome variable Aripiprazole (n=41) Olanzapine (n=45) Quetiapine (n=36) Risperidone (n=135) Weight gain >7% 2 (1-3) 1 (1-2) 2 (1-3) 2 (1-3) Weight gain >14% Weight gain >21% 6 (3- ) 2 (1-4) 3 (2-14) 4 (2-31) 20 (6- ) 4 (2-38) 18 (6- ) 15 (5- ) *Includes 15 untreated comparison patients Data are presented as NNT +/- 95% Confidence Interval Calculated from data in Correll CU et al. JAMA 2009;302:
18 No Age Dependent Weight Gain Relative to Baseline Body Weight at 12-weeks with RIS and OLA in Antipsychotic-Naïve Children, Adolescents and Young Adults aged 4-25 years 30 Risperidone: N=167 R 2 =0.011, p= Olanzapine: N=47 R 2 =0.006, p=0.59 WG % change 3 mo WG % change 3 mo Age Age Correll CU et al. Unpublished data.
19 6-Month Categorical Weight and BMI Z Score Changes with RIS, OLA, QUE and in CTRL Youth 6-month weight gain: RIS: 7.1 kg, OLA: 11.5 kg; QUE: 6.3 kg Arango C et al. J Am Acad Child Adolesc Psychiatry. 2014;53(11):
20 6-Month Categorical Cardiometabolic Changes with RIS, OLA, QUE and in CTRL Youth N= 15 N= 279 N= 157 N= 44 N= 47 N= 15 N= 279 N= 157 N= 44 N= 47 N= 15 N= 279 N= 157 N= 44 N= 47 N= 15 N= 279 N= 157 N= 44 N= 47 b 1) 85th BMI %ile + 1 negative weight-related clinical outcome (blood pressure >90 th percentile, total cholesterol 200 mg/dl, LDL-C >130 mg/dl, HDL-C 40 mg/dl, triglycerides 150 mg/dl, or glucose 100 mg/dl) RIS: youth <12 years (N=32) vs 12 yrs (N=125) higher glucose elevation (p<0.0001) Arango C et al. J Am Acad Child Adolesc Psychiatry. 2014;53(11):
21 Percent Percent De Hert M et al., Clin Pract Epidemol Ment Health. 2006;2:14. Metabolic Syndrome Prevalence in Schizophrenia: Effect of Illness (Treatment) Duration (N=415) N=100 First Episode <1.5 yrs N=130 Recent Onset yrs N=106 Subchronic yrs N=79 Chronic >20 yrs N=100 General Population Age 35-<45 Yrs N=100 Schizophrenia Age 35-<45 Yrs N=100 General Population Age Yrs N=100 Schizophrenia Age Yrs
22 ORs for Diabetes Among Antipsychotic Users vs. Non-Users: Greatest Antipsychotic- Related Risk Among Younger Age Groups Hammerman A et al. Ann Pharmacother (9):
23 Time to T2 Diabetes in Youth on Antipsychotics Antipsychotic Users Vs Psychiatric Controls Antipsychotic Users Vs Healthy Controls Galling B et al. in preparation.
24 Dyslipidemia: TG >150 mg/dl, LDL-C or non-hdl-c: >130 mg/dl; HDL-C for males <40 mg/dl, for females <50 mg/dl Correll CU, et al. JAMA Psychiatry Dec 1;71(12): RAISE: Smoking, Lipid Abnormalities, Hypertension Diabetes + Metabolic Syndrome with Related Drug Rx
25 Dyslipidemia: TG >150 mg/dl, LDL-C or non-hdl-c: >130 mg/dl; HDL-C for males <40 mg/dl, for females <50 mg/dl Correll CU, et al. JAMA Psychiatry Dec 1;71(12): RAISE: Smoking, Lipid Abnormalities, Hypertension Diabetes + Metabolic Syndrome with Related Drug Rx
26 Main Cardiometabolic Baseline Results In first-episode schizophrenia patients, despite similar obesity frequency, smoking and metabolic syndrome were more common than in similarly aged general population adults Dyslipidemia, and pre-hypertension were similar only to general population adults aged years older. Total psychiatric illness duration was significantly associated with higher body composition values (BMI, fat mass & percentage, waist circumference). Even brief antipsychotic treatment duration (47.6 days) was associated with higher metabolic values. Very early cardiometabolic effects were greatest for olanzapine (TG, insulin, HOMA), followed by quetiapine (TG/HDL-C ratio). Correll CU et al. JAMA Psychiatry Oct 8. [Epub ahead of print]
27 Prevalence / Lack of Intervention (%) CATIE: Rates of Pharmacological Interventions for Abnormal Blood Pressure, Lipids and Glucose (CATIE = Clinical Antipsychotic Trials of Intervention Effectiveness) n=1488 n=685 n= n=481 n=300 n=75 n=34 n=471 n=421 Hypertension Diabetes Dyslipidaemia Cases Lack of Medical Intervention Nonwhite men treated more for diabetes (p=0.005) and dyslipidaemia (p=0.014) than nonwhite women Nasrallah H, et al. Schizophr Res 2006:86:15 22
28 Lack of Medical Treatment (%) Self-Reported Lack of Medical Treatment in SMI Patients with Directly Assessed Metabolic Syndrome and Self-Reported Hypertension, Hypercholesterolemia and Diabetes / 1359 Metabolic Syndrome 1646/ 3608 Hypertension 2225/ 3732 Elevated Cholesterol 699/ 1754 Diabetes Correll CU et al. Psych Services Sep;61(9):892-8.
29 TERTIARY PREVENTION SECONDARY PRIMARY Medical Risk Management Strategies of Antipsychotic-Treated Patients Treatment Initiation Healthy lifestyle counseling Healthy lifestyle intervention Start with lower-risk antipsychotic If Adverse Effect Is Present Healthy lifestyle counseling/intervention Consider changing to lower-risk antipsychotic Consider weight loss intervention If Adverse Effect Progresses/Serious Healthy lifestyle counseling/intervention Considering changing to lower-risk antipsychotic Add targeted treatment for pathological values Consider referral to specialist Correll CU. CNS Spectr. Vol 12. No 10 (Suppl 17), 2007 :12-20,35.
30 Conclusions Mentally ill individuals are at increased risk for obesity, metabolic abnormalities and related cardiovascular morbidity/mortality. The risk for physical disorders in psychiatric patients is conferred by mental illness, unhealthy lifestyle and psychiatric treatments. Antipsychotic-induced weight gain leads to predictable medical complications. Effects of prior antipsychotic exposure seem to be more relevant than age for weight gain risk. Interactions between mental and medical illness, development of treatments without cardiometabolic risk and prevention require urgent study.
31 To keep the body in good health is a duty... otherwise we shall not be able to keep our mind strong and clear. Buddha
32 Acknowledgements Patients and their families who participated in the SATIETY and RAISE ETP study or who participated in studies that contributed to the development of these studies NIMH for funding SATIETY and RAISE- ETP, NIMH team for supporting RAISE ETP Community clinicians who referred patients or participated in SATIETY and RAISE-ETP
33 Christoph U. Correll, M.D. The Zucker Hillside Hospital Psychiatry Research rd Street Glen Oaks, New York Tel: Fax:
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