Antipsychotic Medications & Weight Gain Rohan Ganguli, MD, FRCP Professor & Canada Research Chair University of Toronto Executive Vice President Center for Addiction & Mental Health
CONFLICTS OF INTEREST Current• Investments in Pharmaceutical Companies – NONE• Investments in healthcare-related industry – NONE• Slides provided by Pharmaceutical or other companies – NONE
POTENTIAL CONFLICTS OF INTEREST• Research grants - current – Canadian Institutes of Health Research, Public Health Agency of Canada, Canadian Diabetes Association• Research grants - past – National Institute of Mental Health (US), Stanley Research Foundation (US), Eli Lilly, Janssen, Bristol Myers-Squibb, Pfizer• Past Consultations & Speaker’s Honoraria – Janssen, Bristol Myers Squibb, Eli Lilly, Pfizer
WHAT WILL BE PRESENTED?• Evidence for role of antipsychotics in weight gain• Comparison of weight gain risk with different antipsychotics• Treatment and reduction/reversal of anti-psychotic associated adverse metabolic changes
YEARS OF POTENTIAL LIFE LOST Year AZ MO OK RI TX UT VA 1997 26.3 25.1 28.5Average years of life lost=25 years 1998 27.3 25.1 28.8 29.3 15.5 1999 32.2 26.8 26.3 29.3 26.9 14.0 2000 31.8 27.9 24.9 13.5Sixteen-State Study on Mental Health Performance MeasuresParks et al., Nat Assoc State Mental Health Program Directors, 2006
“CATIE STUDY”: Prevalence ofMetabolic Syndrome at Baseline * 60 CATIE (N = 689) 50 NHANES (N = 687) * % with MetS 40 30 20 10 0 NHANES = National Health and Nutrition Examination Survey. *P = 0.0001 CATIE vs NHANES. Males FemalesMcEvoy JP, et al. Schizophr Res. 2005; 80:19-32 Rohan Ganguli, M.D.
Prevalence of Metabolic Syndrome in Clozapine Patients 60 53.8 % with MetS 40 20.7 20 0 Controls Clozapine Patients Lamberti JS, et al., Am J Psychiatry. 2006; 163:1273-1276
RISK OF METABOLIC SYNDROME:HIGHLY CORRELATED WITH BODY MASS (weight) N=12,363 Healthy 70 Overweight Obese 60Prevalence (%) 50 40 Men Women 30 20 10 0 Healthy=BMI ≤25 kg/m2 ; Overweight=BMI 25-29.9 kg/m2; Obese=BMI ≥30 kg/m2. Park YW et al. Arch Intern Med. 2003;163:427-436. Rohan Ganguli, M.D.
BMI among ambulatory schizophrenia patients N=276 19% NORMAL WEIGHT OVER WEIGHT OBESE 59% 22% Normal weight: BMI 19-25 Overweight: BMI 25-30 Obese: BMI >30Strassing M, Brar JS, Ganguli R. Schizophr Bull. 2003;29:393-397.
COMPREHENSIVE RESEARCH SYNTHESIS OF ANTIPSYCHOTIC-INDUCED WEIGHT GAINAllison et al., Am J Psychiatry,Rohan 156, 1999 Vol Ganguli, M.D.
Conclusions• Antipsychotic medications vary in terms of the risk of weigh gain associated with their use• This needs to be discussed with a patient and her/his caregivers, when initiating treatment – And the risks of alternatives also need to be presented• If a patient is gaining weight on a high risk medication, can switching to a low risk medication help?
Switching to Aripiprazole Ganguli et al. Clin. Schizophrenia & Related Psychoses, 201133 schizophrenia patients who hadgained weight, and who agreed toswitch from other antipsychotics toaripiprazole in an open, flexible-dose,eight-week trial
Switching to aripiprazole Ganguli et al. Clin. Schizophrenia & Related Psychoses, 2011Metabolic changes, based on antipsychotic prior to switching
Switching to aripiprazoleStroup et al. American J Psychiatry, 2011
Switching to aripiprazoleStroup et al. American J Psychiatry, 2011 Weight & Lipid Changes
Switching to aripiprazoleStroup et al. American J Psychiatry, 2011 Treatment Discontinuation
Prevention of Antipsychotic- Associated Weight Gain• 49 patients with schizophrenia or schizoaffective disorder – Starting a novel antipsychotic • Risperidone, olanzapine, quetiapine, ziprasidone, clozapine• Randomized to – “intervention” – stepped care, based on observed weight gain – “usual care” – weight monthly• Follow up for 16 weeksGanguli R, Brar JS. Schizophr Bull. 2005;31:561.
Prevention of Weight Gain Stepped Interventions• STEP 1 – self-monitoring • daily weight, food consumed and physical activity – controlling urges to overeat and snack • covert procedures & limiting eating to one area• STEP 2 – decreasing food cues – developing good eating habits – self-control of overeating• STEP 3 – Exercise• STEP 4 – changing snack habits Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.
Prevention of Weight Gain Results 10 8Final – baseline weight in kg 6 (P=.003) 4 2 0 Control -2 -4 Treatment Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.
Behavior Therapy to Prevent Weight Gain 100 No Some weight weight gain gain No Gain 50 GainIntervention 17 10Control 5 17 0 Intervention ControlP = 0.009 Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.
Conclusions Primary prevention• Recommend and use agents with the lowest potential for adverse metabolic effects• Discuss possibility of weight gain and suggest strategies to prevent this • Self monitoring • Nutrition • Physical activity
Conclusions Secondary PreventionMonitor weight at regular intervals (at the very least) – Monitor lipid and fasting blood sugar/HbA1c at least annually
Conclusions Secondary Prevention• Switching from metabolically high risk to low risk medications should be considered – and presented to patient (and caregiver) as an option• The probability of metabolic benefit must be weighed against the risk of worsening or relapse
Conclusions Tertiary Prevention• Refer individuals who have gained weight to programs which specialize in weight loss interventions – Or develop these in your program• Make sure that your patients have primary care physicians for treatment of metabolic complications – And that the see them regularly – And that you collaborate with the PCP