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Presented at the first Obesity and Mental Health Conference, Toronto June 2012
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Antipsychotic Medications & Weight Gain
Rohan Ganguli, MD, FRCPProfessor & Canada Research Chair
University of Toronto
Executive Vice President
Center for Addiction & Mental Health
CONFLICTS OF INTERESTCurrent
• 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 28.5
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
Average years of life lost=25 years
Rohan Ganguli, M.D.
NHANES = National Health and Nutrition Examination Survey. * P = 0.0001 CATIE vs NHANES.
0
10
20
30
40
50
60
Males Females
% w
ith
Met
S
*
*
CATIE (N = 689)
NHANES (N = 687)
McEvoy JP, et al. Schizophr Res. 2005; 80:19-32
“CATIE STUDY”: Prevalence of Metabolic Syndrome at Baseline
Prevalence of Metabolic Syndrome in Clozapine Patients
20.7
53.8
0
20
40
60
% w
ith
Me
tS
Controls Clozapine Patients
Lamberti JS, et al., Am J Psychiatry. 2006; 163:1273-1276
Rohan Ganguli, M.D.
RISK OF METABOLIC SYNDROME: HIGHLY CORRELATED WITH BODY MASS (weight)
Healthy=BMI ≤25 kg/m2 ; Overweight=BMI 25-29.9 kg/m2; Obese=BMI ≥30 kg/m2.
Men Women
0
10
20
30
40
50
60
70
Pre
vale
nce
(%
)
HealthyOverweightObese
N=12,363
Park YW et al. Arch Intern Med. 2003;163:427-436.
BMI among ambulatory schizophrenia patients
19%
22%59%
NORMAL WEIGHT
OVER WEIGHT
OBESE
Normal weight: BMI 19-25Overweight: BMI 25-30Obese: BMI >30
N=276
Strassing M, Brar JS, Ganguli R. Schizophr Bull. 2003;29:393-397.
Rohan Ganguli, M.D.
COMPREHENSIVE RESEARCH SYNTHESIS OF ANTIPSYCHOTIC-INDUCED WEIGHT GAIN
Allison et al., Am J Psychiatry, Vol 156, 1999
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?
Conventionals OlanzapineRisperidone
-25
-20
-15
-10
-5
0
5
LS
Mea
n C
han
ge
(lb
)
49 53 584540363227231914106
*
***
***
**
**
***
*P<0.05 **P<0.01***P<0.0001
Switched from
Switching to ziprasidoneWeiden et al., Neuropsychopharmacology 2008
Switching to Aripiprazole Ganguli et al. Clin. Schizophrenia & Related
Psychoses, 201133 schizophrenia patients who had gained weight, and who agreed to switch from other antipsychotics to aripiprazole in an open, flexible-dose, eight-week trial
Switching to aripiprazole Ganguli et al. Clin. Schizophrenia & Related
Psychoses, 2011
Metabolic 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 & LipidChanges
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 weeks
Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.
Prevention of Weight GainStepped 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 GainResults
Ganguli R, Brar JS. Schizophr Bull. 2005;31:561.
0
-2
-4
4
2
8
6
10
(P=.003)
Fin
al –
bas
elin
e w
eig
ht
in k
g
Treatment
Control
Behavior Therapy to Prevent Weight Gain
0
50
100
Intervention Control
No Gain
Gain
No weight
gain
Some weight
gain
Intervention 17 10
Control 5 17
P = 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
ConclusionsSecondary Prevention
Monitor 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
ConclusionsTertiary 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
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