Introduction. Objectives. Psychotropic Medications & Cardiometabolic Risk

Transcription

1 Psychotropic Medications & Cardiometabolic Risk Sam Ellis, PharmD, BCPS, CDE Associate Professor University of Colorado School of Pharmacy Introduction Second GenerationAntipsychotics (SGA) first FDA approved less than 20 years ago Significantly less use of 1 st generation antipsychotic medications and related adverse drug events (ADE) AAPs introduced new ADE Significant variability exists among the SGA Objectives Describe the various SGA medications and their associated metabolic ADE List the differences in metabolic ADE among the various SGA Recommend a metabolic monitoring plan for patients starting SGA medications Determine possible preventative strategies for reducing metabolic abnormalities in patients taking SGA medications

2 Patient Case A 46 year old female presents to clinic after starting quetiapine XR (Seroquel XR) 300mg daily for add on therapy to sertraline for the management of Major Depressive Disorder (MDD). She started on 150mg daily x 1 month and this was increased 5 months ago to 300mg daily. She has been having a positive benefit over the past 4 months with the addition of this medication PMH: Depression, hypertension Medications: sertraline 150mg daily, lisinopril/hctz 20/25mg daily Social Hx: smoker, occasional ETOH, sedentary lifestyle Family Hx: father died at 66 yo from complications related to DM, mother HTN, Dyslipidemia Vitals: BP 144/86 mmhg Wt: 197 (up 8 lbs) BMI 31.9 Fasting Labs: Glucose: 133mg/dl TC 249 mg/dl (210 mg/dl last year) AST 27U/L TG 238 mg/dl (112 mg/dl last year) HDL 44 mg/dl (49 mg/dl last year) LDL 157mg/dl (139 mg/dl last year) Prevalence of Serious Mental Illness Among US Adults Almost 5% of US population with serious mental illness (SMI) Majority of patients with SMI receive prescription treatment Highest prevalence among younger female patients Psychiatric Patients and Medical Co-Morbidity Risk factors for cardiovascular disorders and rates of physical disorders are increased in the psychiatric population, partly due to low levels of help-seeking and lifestyle factors, poor diet, reduced of physical activity, smoking and medications Phelan, Stradins & Morrison(2001) Physical health of people with severe mental illness. BMJ 322:443-4

3 Smoking Physical Inactivity Schizophrenia and the Metabolic Highway Regardless of antipsychotic use, schizophrenia patients are at greater risk of developing diabetes and cardiovascular disease than the general population Overweight/Obese Alcohol Consumption Diabetes Family History of Diabetes 5x more likely ½ as likely to do light exercise ¼ as likely to do vigorous exercise 8x more likely 2x as likely to abstain 4x more likely to drink harmful amounts 1.5 2x greater prevalence 6x more likely American Diabetes Association et al. Consensus statement. Diabetes Care 2004.; Kabinoff GS et al. J Clin Psychiatry 2003.; Cavazzoni P et al. Br J Psychiatry 2004.; Kirn TF. Critical Psychiatry News Davidson S. Anz J Psych Cardiovascular Disease Risk Factors 45%-55%, 1.5-2X RR 1 26% 5 50%-80%, 2-3X RR 2 55% 6 10%-14%, 2X RR 3 10% 7 18% 4 15% 5 Up to 5X RR 8,9 1. Davidson S et al. Aust N Z J Psychiatry. 2001;35: Allison DB et al. J Clin Psychiatry. 1999;60: Dixon L et al. J Nerv Ment Dis. 1999;187: Herran A et al. Schizophr Res. 2000;41: McElroy SL et al. J Clin Psychiatry. 2002;63: Ucok A et al. Psychiatry Clin Neurosci. 2004;58: Cassidy F et al. Am J Psychiatry. 1999;156: Allebeck P. Schizophr Bull. 1989;15: Koro CE et al. Arch Gen Psychiatry. 2002;59: Second Generation Antipsychotics (SGA) Trade Name Generic Indication Schizophrenia Bipolar Dz MDD Abilify aripiprazole X X X (adjunct) Clozaril clozapine X Fanapt iloperidone X Geodon ziprasidone X X Invega paliperidone X Latuda lurasidone X Risperdal risperidone X X Seroquel quetiapine X X X (adjunct) Zyprexia olanzapine

4 Metabolic Effects of SGA Medications Associated with: Weight gain Diabetes Dyslipidemia Metabolic Syndrome? CAD Mechanisms of Increased Metabolic Risk Weight Gain: antihistamine, antimuscarinic and 5-HT2c receptor effects Genetic predispositions Lifestyle Free Fatty Acids, adipocytokines Insulin Resistance Insulin Resistance Obesity Metabolic Syndrome Diabetes 2 x 4 x Cardio Vascular Disease (CVD) Reilly MP et al Circulation 2003; 108:

5 CATIE Study: Weight Gain Evaluate the overall effectiveness and persistence of four 2 nd generation and one 1 st generation antipsychotic medication Secondary outcomes were evaluating metabolic changes of these drugs including weight gain Adverse Events of Antipsychotics: CATIE Study Percent of Patients (%) Weight Gain with SGA Incidence of 7% Increase in Body Weight in Short-Term Trials* Placebo Aripiprazole** Paliperidone ER*** Ziprasidone Risperidone Quetiapine Olanzapine *Based on USPIs **Error bars reflect reporting of weight gain in PI by baseline BMI ***Based on SCH-303, 304, 305 pooled dataset (all doses)

6 Reasons for discontinuation of antipsychotic medication Patients with medication change (%)* Positive Negative Weight gain Somnolence EPS Prolactin N=1582 Symptoms AEs *Percentages based on total number of subjects ever having received antipsychotic medication; more than one reason could be cited. Adapted from Tandon R et al. Schizophr Res. 2006;84:77-89 Increased Visceral Fat in Medication-Free Schizophrenics: Computed Tomography (CT) Findings 40,000 Fat (mm 2 ) 35,000 30,000 25,000 20,000 15,000 10,000 5,000 0 Controls n=15 Schizophrenics n=15 Total Body Fat Subcutaneous Fat Intra-Abdominal Fat p<0.12 p<0.68 *p<0.005 * Thakore JH et al. Int J Obes Relat Metab Disord Risk of Developing Diabetes with SGA Medications Short term studies show small increase (1-2%) in euglycemic patients to BG 126mg/dl Much greater in patients with pre-dm ranges ( mg/dl). Dose related for most SGA medications

7 Diabetes Incidence by Number of Metabolic Syndrome Components Subjects with Event (%) Factors 12 3 Factors 10 2 Factors 8 1 Factor 6 0 Factors Year Diabetes risk increases synergistically when at least four risk factors are present; risk factors evaluated comprise metabolic syndrome symptom clusters; those factors are increased waist circumference, blood pressure, triglyceride, and fasting glucose levels as well as decreased high-density lipoprotein levels Sattar N et al. Circulation In: Sacks FM. J Clin Psychiatry HTN Associated with SGA Medications CATIE Study Matched Controls with NHANES data Confounding factors Sedentary Smoking Obese Medications Dyslipidemia and SGA Medication Use

8 Patient Case Assess cardiometabolic risk factors in this patient Does she have metabolic syndrome What is her calculated risk score Atypical Antipsychotics and Risk Cardiometabolic Increased appetite Weight gain Insulin resistance Hyperinsulinemia Beta-cell failure Pre-diabetes Antipsychotic Diabetes Antipsychotic Antipsychotic Cardiovascular events -10 to Years Copyright 2006 Neuroscience Education Institute. All rights reserved. Figure reproduced, with permission from SM Stahl and N Muntner.; Stahl SM. Essential Psychopharmacology. 3rd ed. In preparation.; Newcomer JW. CNS Drugs. 2005;19(suppl 1):1-93. Premature death and loss of years of normal life span Monitor CV Risk Factors in Patients Using SGA premature death and loss of years of normal lifespan RIP monitor antipsychotic monitor antipsychotic insulin resistance beta cell failure hyperinsulinemia diabetes pre-diabetes cardiovascular events increased appetite obesity and increased fat mass weight gain raised triglycerides BEWARE: cardiometabolic risk ahead 24 monitor antipsychotic

9 Increase in Framingham Risk Scores during CATIE Study Patient Case What is this individuals Framingham Risk Score now on SGA therapy? What does this mean for CAD prevention SGA Medications: What Should We Monitoring and When Joint Guidelines from the American Diabetes Association and the American Psychiatric Association (Diabetes Care 27: , 2004).

10 ADA/APA Monitoring for Patients on Atypical Antipsychotics Baseline 4 weeks 8 weeks 12 weeks Quarterly Annually Every 5 years Personal/family history + + Weight (BMI) Waist circumference + + Blood pressure Fasting plasma glucose Fasting lipid profile American Diabetes Association et al. Consensus Statement. Diabetes Care Can We Prevent Metabolic ADE of SGA Medications Weight Loss Medications Metformin Goals of SGA Therapy Treat the underlying condition Identifying agents that decrease risk of inducing CV risk factors Tailor therapies to the patient Avoid giving medications to treat ADE

11 Strategies to Prevent Adverse Metabolic Outcomes Work closely with mental health experts Monitor closely according to ADA/APA Educate patient about prevention strategies and refer when necessary Consider pharmacologic strategies when absolutely necessary