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

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%

Metabolic Effects of Atypical Agents

Lieberman et al. New Eng J Med 2005 and Allison et al. Am J Psych1999

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

Metformin for Antipsychotic-Induced Weight Gain in Youth

-2

0

2

4

6

0 4 8 12 16

Metformin

Placebo

MeanWeightChangeIn kg

Weeks

N= 39 youth, mean age 13, gained >10% body weight on OLZ, RISP, QUETRCT metformin 500 – 850mg bid or like placebo; ADRs similar both groups

Klein DJ, et al. Am Journal of Psychiatry 2006

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 1st 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

Lifestyle Intervention & Metformin for Antipsychotic Induced Weight Gain

N= 128Schizophrenia

for 9 yearsMean age – 26

OlanzapineRisperidone

Sulpiride

Lifestyle/ Metforminn= 32

Wt kg ( -4.7)BMI ( - 1.8)Waist (-2.0)

Insulin (-13.9)IRI ( - 3.5 )

Metforminn= 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)

Placebon= 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. differences5 exacerbations of psychosis2 in placebo group developeddiabetes at week 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