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