1. The Biggest Loser Challenge: A Pill for Atypical Antipsychotic Induced-Weight Gain? Julie A. Dopheide, Pharm.D., BCPP Associate Professor of Clinical Pharmacy, Psychiatry and the Behavioral Sciences, University of Southern California Schools of Pharmacy and Medicine

2. Relative Risk of Weight Gain  Ziprasidone (Geodon)  Aripiprazole (Abilify)  Risperidone (Risperdal)  Quetiapine (Seroquel)  Olanzapine (Zyprexa)  Clozapine (Clozapine) Low Moderate High Wu Ren-Rong et al. JAMA 2008, Brooks JO et al. Current Psych Reports 2009 78.8% of patients receiving antipsychotics increase baseline weight by >7%

3. Metabolic Effects of Atypical Agents Lieberman et al. New Eng J Med 2005 and Allison et al. Am J Psych1999

4. Treatment Options for Antipsychotic Induced Weight Gain  Diet and exercise  Appetite suppressants (psychostimulants, sibutramine)  Blocks fat absorption – orlistat  Blocks glucose production and improves insulin sensitivity - metformin

5. Metformin for Antipsychotic-Induced Weight Gain in Youth Mean Weight Change In kg Weeks N= 39 youth, mean age 13, gained >10% body weight on OLZ, RISP, QUET RCT metformin 500 – 850mg bid or like placebo; ADRs similar both groups Klein DJ, et al. Am Journal of Psychiatry 2006

6. Lifestyle Intervention & Metformin for Antipsychotic Induced Weight Gain  RCT: 12 weeks, Oct 2004 – Dec 2006, China  N= 128, Diagnosis: Schizophrenia  Gained > 10% of baseline weight during 1 st yr  Randomized into 4 groups  Metformin 750mg/day + lifestyle intervention  Metformin 750mg/day alone  Lifestyle intervention + placebo  Placebo  Outcome Measures: BMI, insulin levels, insulin resistance index (IRI), waist circumference Wu Ren-Rong et al. JAMA 2008

7. Lifestyle Intervention & Metformin for Antipsychotic Induced Weight Gain N= 128 Schizophrenia for 9 years Mean age – 26 Olanzapine Risperidone Sulpiride Lifestyle/ Metformin n= 32 Wt kg ( -4.7) BMI ( - 1.8) Waist (-2.0) Insulin (-13.9) IRI ( - 3.5 ) Metformin n= 32 Wt kg (-3.2) BMI (-1.2) Waist (-1.3) Insulin (-12.7) IRI (-3.5) Lifestyle+ Placebo n= 32 Wt kg (-1.4) BMI (-0.5) Waist (0.1) Insulin (-2.7) IRI (-1.0) Placebo n= 32 Wt Kg (3.1) BMI (1.2) Waist (2.2) Insulin (2.1) IRI (0.4) Results: All treatments better than placebo. Best outcome: Lifestyle+metformin (p<0.001 ) ADRs: No sig. differences 5 exacerbations of psychosis 2 in placebo group developed diabetes at week 8

8. When to Consider Metformin  > 7% weight gain over baseline  Good renal function - stable  Positive antipsychotic response requires ongoing treatment  Start low at 250 – 500mg x 1 week, can increase as tolerated  Encourage Lifestyle Intervention