The document discusses the risks of weight gain and metabolic side effects from different antipsychotic medications, recommends monitoring weight and metabolic markers when prescribing antipsychotics, and outlines strategies for preventing and managing antipsychotic-induced weight gain through lifestyle interventions, switching medications, and collaboration with primary care physicians.

1. Antipsychotic Medications &
Weight Gain
Rohan Ganguli, MD, FRCP
Professor & Canada Research Chair
University of Toronto
Executive Vice President
Center for Addiction & Mental Health

2. CONFLICTS OF INTEREST
Current
• Investments in Pharmaceutical
Companies
– NONE
• Investments in healthcare-related industry
– NONE
• Slides provided by Pharmaceutical or
other companies
– NONE

3. 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

4. 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

5. YEARS OF POTENTIAL LIFE
LOST
Year AZ MO OK RI TX UT VA
1997 26.3 25.1 28.5
Average 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 13.5
Sixteen-State Study on Mental Health Performance Measures
Parks et al., Nat Assoc State Mental Health Program Directors, 2006

6. “CATIE STUDY”: Prevalence of
Metabolic 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 Females
McEvoy JP, et al. Schizophr Res. 2005; 80:19-32 Rohan Ganguli, M.D.

7. 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

8. RISK OF METABOLIC SYNDROME:
HIGHLY CORRELATED WITH BODY MASS (weight)
N=12,363 Healthy
70 Overweight
Obese
60
Prevalence (%)
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.

9. 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 >30
Strassing M, Brar JS, Ganguli R. Schizophr Bull. 2003;29:393-397.

10. COMPREHENSIVE RESEARCH SYNTHESIS OF
ANTIPSYCHOTIC-INDUCED WEIGHT GAIN
Allison et al., Am J Psychiatry,Rohan 156, 1999
Vol Ganguli, M.D.

11. 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?

12. Switching to ziprasidone
Weiden et al., Neuropsychopharmacology 2008
6 10 14 19 23 27 32 36 40 45 49 53 58
5
LS Mean Change (lb)
0 *
-5 ***
**
-10
*** **
-15
*P<0.05
**P<0.01
-20
***P<0.0001
***
-25 Switched from
Conventionals Risperidone Olanzapine

13. Switching to Aripiprazole
Ganguli et al. Clin. Schizophrenia & Related
Psychoses, 2011
33 schizophrenia patients who had
gained weight, and who agreed to
switch from other antipsychotics to
aripiprazole in an open, flexible-dose,
eight-week trial

14. Switching to aripiprazole
Ganguli et al. Clin. Schizophrenia & Related
Psychoses, 2011
Metabolic changes, based on antipsychotic prior to switching

15. Switching to aripiprazole
Stroup et al. American J Psychiatry, 2011

16. Switching to aripiprazole
Stroup et al. American J Psychiatry, 2011
Weight & Lipid
Changes

17. Switching to aripiprazole
Stroup et al. American J Psychiatry, 2011
Treatment
Discontinuation

18. 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 weeks
Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.

19. 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.

20. Prevention of Weight Gain
Results
10
8
Final – baseline weight in kg
6 (P=.003)
4
2
0
Control
-2
-4 Treatment
Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.

21. Behavior Therapy to Prevent
Weight Gain
100
No Some
weight weight
gain gain
No Gain
50
Gain
Intervention 17 10
Control 5 17
0
Intervention Control
P = 0.009
Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.

22. 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

23. Conclusions
Secondary Prevention
Monitor weight at regular intervals (at the
very least)
– Monitor lipid and fasting blood
sugar/HbA1c at least annually

24. 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

25. 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