1. MIAMI: MIRECC Initiative on Antipsychotic Management Improvement Metabolic Monitoring and Management of Antipsychotic Medication

2. Comorbidity and Mortality in Patients With Serious Mental Illness Patients, % 50% increased risk of death from medical causes in schizophrenia (20% shorter lifespan; die approximately 10 years younger)

3. Obesity in Patients With Schizophrenia Prevalence of overweight patients with schizophrenia (BMI ≥25) is 42%. Obesity Disability Premature death Diabetes mellitus Coronary artery disease Hypertension Gallbladder disease Osteoarthritis Several types of tumors

4. The Metabolic Syndrome

5. Metabolic Syndrome in Patients With Schizophrenia  Metabolic syndrome is a constellation of abnormal physiologic conditions characterized by:  Increased body weight  Glucose intolerance  Dyslipidemia  Hypertension  High prevalence in patients who receive SGAs (varies by antipsychotic agent)  Antipsychotic polypharmacy has been associated with higher rates of metabolic syndrome Patients, %

6. Metabolic Abnormalities With Second-Generation Antipsychotics +: increase –: no effect +/--: discrepant results

7. Weight Gain: Second-Generation Antipsychotics Versus Placebo Clinically Significant (≥7%) Weight Gain During Antipsychotic Treatment Placebo Aripiprazole Quetiapine Clozapine Ziprasidone Paliperidone Incidence, % Placebo Risperidone Placebo Olanzapine

8. Mean Glucose Change by Antipsychotic Medication (CATIE Results) Glucose (mg/dL) Glycosylated Hg (% HgA1c) 13.7 0.11 2.9 0.0 5.4 0.07 6.6 0.04 7.5 0.4 olanzapinerisperidoneperphenizinequetiapineziprasidone

9. Change in Cholesterol and Triglyceride Levels by Antipsychotic Medication (CATIE Results) Olanzapine Perphenazine Quetiapine Risperidone Ziprasidone Cholesterol and Triglycerides Change, mg/dL Cholesterol Triglycerides

10. Change in Metabolic Syndrome by Antipsychotic Medication (CATIE Results) Olanzapine Risperidone Quetiapine Ziprasidone Perphenazine a Proportion of Patients, % a At 3 months, patients taking olanzapine showed a significant increase in metabolic syndrome. Those treated with ziprasidone had the greatest reduction.

11. VA Monitoring Protocol in Patients Receiving Second-Generation Antipsychotics More frequent assessments should be conducted for those who have gained more than 5% of their body weight (approximately 7.5 pounds for most people). Baseline 4 Weeks 8 Weeks 12 Weeks 3 MonthsYearly Medical historyX X Weight (BMI)XXXXXX Blood pressureX X X Fasting plasma glucose or HgA1c X X X Fasting lipidsX X X

12. Body Mass Index Chart

13. Intervention for Overweight Patients on Antipsychotic Medication  Refer to a weight management program  Consider switching to medication with less weight gain liability  Switching SGA should be considered if patient gains ≥5% of baseline body weight (approximately 7.5 pounds for most people)  Abrupt discontinuation of SGAs should be avoided  Discontinuing clozapine should be carefully considered due to the potential for serious psychiatric sequelae  For patients with worsening glycemia or dyslipidemia, it is recommended that switching to an FGA or an SGA that has not been associated with significant weight gain or diabetes (i.e., ziprasidone and aripiprazole) should be considered

14. Psychosocial Weight Management Programs  Review of 11 studies targeting weight loss among individuals with schizophrenia-spectrum disorders  Compared psychosocial weight intervention to control condition  10 of the 11 studies found support for modest weight loss  Mean weight loss of 5 pounds across all 10 studies  Weight loss ranged from 1-7 pounds  Treatment may include:  Psychoeducation regarding diet and exercise  Goal setting  Self-monitoring of food and physical activity level  Caloric restriction  Increase in physical activity

15. Weight Loss Due to Medication Switch: CATIE Study  Patients who gained more than 7% of their body weight in Phase 1 had their medication switched.  Switching resulted in greater weight loss for some medications than others.  Switch to Olanzapine: 0% lost greater than 7% of their weight  Switch to Quetiapine: 7% lost greater than 7% of their weight  Switch to Risperdone: 20% lost greater than 7% of their weight  Switch to Ziprasidone: 42% lost greater than 7% of their weight

16. Weight Loss Due to Medication Switch: Newcomer Study (2008)  Overweight patients on olanzapine  Switch to aripiprazole vs. remain on olanzapine  RCT, n=173, 16 weeks  Results  Weight change (pounds): -4.0 vs. +3.1  Lost more than 7% of body weight: 11.1% vs. 2.6%  Lipids improved, glucose unaffected  CGI-Improvement: no change - minimal improvement

17. How to Know When to Refer to Primary Care  Blood Glucose  If fasting glucose is between 110 and 126 mg/dl or is > 126 with HgbA1c < 7%: Counsel on diet/exercise, re-evaluate pharmacotherapy, and recheck blood sugar at a reasonable interval  If fasting glucose is 126-199 and HgbA1c > 7%: Refer to primary care  If fasting glucose is > 200 or symptoms of diabetes: Urgent follow- up with primary care for consult  Lipids  If test reveals an increase in LDL that is clinically significant but still below 160, more frequent monitoring is recommended  If LDL >160: Refer to primary care  Treatment/referral decision must consider risk factors in addition to lab values (see table of recommendation for LDL)

18. Recommendations for LDL Risk Category *LDL Goal (mg/dL) Initiate Therapeutic Lifestyle Changes (mg/dL) Consider Drug Therapy High risk: CAD or CAD equivalents** (10-year risk > 20%) < 100 (aggressive goal: < 70) ≥100≥130 (100-129: consider drug options) Moderately high risk: 2+ risk factors (10-year risk 10-20%) < 130≥130 Moderate risk: 2+ risk factors (10-year risk < 10%) < 130≥130≥160 Low risk: 0-1 risk factor < 160≥160≥190 (160-189: LDL-lowering drug optional *Risk factors: tobacco use, HTN, family history, age (> 45 ♂, > 55 ♀ ), HDL (< 40 ♂, < 50 ♀) **CAD equivalents: diabetes, abdominal aortic aneurysm, peripheral or coronary artery disease, carotid artery stenosis

19. How to Know When to Refer to Primary Care  Blood Pressure  BP 120-139/80-89: Counsel on diet/exercise, re-evaluate pharmacotherapy, and recheck at next visit  BP > 130/80: Refer to primary care if patient has any of the following co-occurring diseases: Diabetes Chronic kidney disease Cerebrovascular disease Coronary artery disease  BP > 140/90: Refer to primary care

20. Recommendations for Blood Pressure Initial Drug Therapy BP Classification SBP MMHG DBP MMHG Lifestyle Modification Without Compelling Indication With Compelling Indications Normal< 120and < 80Encourage No antihypertensive drug indicated. Drug(s) for compelling indications. Prehypertension120-139or 80-89Yes Stage 1 Hypertension 140-159or 90-99Yes Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Drug(s) for the compelling indications. Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Stage 2 Hypertension ≥ 160or ≥ 100Yes Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB).

21. MIAMI: MIRECC Initiative on Antipsychotic Management Improvement  Educational materials and implementation tools are available at http://vaww.mirecc.va.gov/miamiproject/http://vaww.mirecc.va.gov/miamiproject/  A technical assistance center is available to offer clinical consultation on metabolic effects of antipsychotics, advice about effective implementation strategies, and access to additional educational materials. Contact us:  Toll free number: 1-888-357-1978  E-mail: vhalitmiamiproject@va.govvhalitmiamiproject@va.gov