Obesity treated strategy and clinical practice in psychiatric disease related obesity 中國醫藥大學附設醫院精神醫學部黃介良 psyche@

Obesity treated strategy and clinical practice in psychiatric disease related obesity

中國醫藥大學附設醫院精神醫學部

黃介良[email protected]

Psychiatric illness related Obesity Substance use disorder Nicotine

Men with a former nicotine dependence had higher odds of being overweight than men who never had a nicotine dependence (adjusted odds ratio, 1.5; confidence interval, 1.1 to 2.1)

Alcohol Men at current risk for drinking and current

alcohol-dependent or abusing men had lower odds of being overweight compared with men who never were alcohol dependent, abusing, or at risk for drinking (adjusted odds ratio, 0.3; confidence interval, 0.8 to 0.9).

John U et al., OBESITY RESEARCH,13, 101-109, 2005

Psychiatric illness related Obesity Major depression

No relationship of overweight with depressive, anxiety, or somatoform disorders was found in the multivariate analysis. 1

obesity is associated with depression mainly among persons with severe obesity 2

1. John U et al., OBESITY RESEARCH,13, 101-109, 20052. Onyike CU et al., Am J Epidemiol 2003;158:1139–1147

Psychiatric illness related Obesity bipolar affective disorder Patients with bipolar disorder appear to be at g

reater risk than the general population for overweight and obesity 1,2

Risk factor:1 Comorbid binge-eating disorder the number of depressive episodes treatment with medications associated with weight g

ain alone or in combination; excessive carbohydrate con

sumption low rates of exercise

1.Keck PE et al.,J Clin Psychiatry. 2003 Dec;64(12):1426-35.2. McElroy SL et al.,J Clin Psychiatry. 2002 Mar;63(3):207-13.

Allison DB et al. J Clin Psychiatry. 1999;60:215-220.

Pe

r ce

nt

Pe

rce

nt

< 18.518.5-20 20-22 22-24 24-26 26-28 28-30 30-32 32-34 > 34

0

10

20

30

No schizophrenia

Schizophrenia

Obese Overweight Acceptable Under-weight

BMI RangeBMI Range

BMI Distributions for General Population and Those With Schizophrenia (1989)

Psychiatric illness related ObesityCause

Disease itself Lifestyle Psychotropic effect


Psychiatric illness in Obesity population

Obesity (BMI>30) was associated with significant increases in lifetime

diagnosis of major depression (odds ratio [OR], 1.21; 95% confidence

interval [CI], 1.09-1.35), bipolar disorder (OR, 1.47; 95% CI, 1.12-1.93), panic disorder or agoraphobia (OR, 1.27; 95% CI, 1.01-

1.60). significantly lower lifetime risk of

substance use disorder (OR, 0.78; 95% CI, 0.65-0.93).

Simon GEet al., Arch Gen Psychiatry. 2006;63:824-830

Simon GEet al., Arch Gen Psychiatry. 2006;63:824-830

Psychiatric illness in Obesity population

Obesity Among women,

increased BMI was associated with both major depression and suicide ideation.

Among men, lower BMI was associated with major

depression, suicide attempts, and suicide ideation.

Kenneth M.et al., Am J Public Health. 2000;90:251–257

Mokdad et al. Diabetes Care. 2000;23:1278.Mokdad et al. JAMA. 1999;282:1519.Mokdad et al. JAMA. 2001;286:1195.

72

73

74

75

76

77

78

4.04.55.05.56.06.57.07.5

1990 1992 1994 1996 1998 2000

Pre

vale

nc

e (

%)

Pre

vale

nc

e (

%)

DiabetesMean body weight

kg

YearYear

Diabetes and Obesity: The Continuing Epidemic

Cardiovascular Disease (CVD) Risk Factors

Modifiable Risk Factors

Estimated Prevalence and Relative Risk (RR)

SchizophreniaBipolar

Disorder

Obesity45–55%, 1.5-2X

RR1 26%5

Smoking 50–80%, 2-3X

RR2 55%6

Diabetes 10–14%, 2X RR3 10%7

Hypertension ≥18%4 15%5

Dyslipidemia Up to 5X RR8

1. Davidson S, et al. Aust N Z J Psychiatry. 2001;35:196-202. 2. Allison DB, et al. J Clin Psychiatry. 1999; 60:215-220. 3. Dixon L, et al. J Nerv Ment Dis. 1999;187:496-502. 4. Herran A, et al. Schizophr Res. 2000;41:373-381. 5. MeElroy SL, et al. J Clin Psychiatry. 2002;63:207-213. 6. Ucok A, et al. Psychiatry Clin Neurosci. 2004;58:434-437. 7. Cassidy F, et al. Am J Psychiatry. 1999;156:1417-1420. 8. Allebeck. Schizophr Bull. 1999;15(1)81-89.

Psychiatric illness related ObesityCause

Disease itself Lifestyle Psychotropic effect


Body Weight Changes AssociatedWith Psychopharmacology

Malhi GS, Australian and New Zealand Journal of Psychiatry 2001; 35:315–321

Body Weight Changes AssociatedWith Psychopharmacology-1

Vanina Y. Psychiatric Services 53:842–847, 2002

Medication Effect on WeightAntipsychotic drugsChlorpromazineThioridazineFluphenazineHaloperidolPerphenazinePimozideLoxapineMolindoneClozapineOlanzapineQuetiapineRisperidoneZiprasidone

++++++++++Not clear–+++++++++++



Medication Effect on Weight

Mood stabilizersValproate productsLithiumCarbamazepineGabapentinLamotrigineTopiramate

++++++++++Not clear–




Antidepressant drugs-1AmitriptylineImipramineNortriptylineProtriptylineTrimipramineDesipraminePhenelzineTranylcypromineIsocarboxazid

+++++++Not clearNot clearNot clearNo change+No change–




Antidepressant drugs-2MirtazapineCitalopramFluoxetineSertralineTrazodoneFluvoxamineParoxetineVenlafaxineBupropionNefazodone

+++Not clearNot clearNot clearNot clearNot knownNot knownNo change––




Antiparkinsonian drugsAmantadineBiperidineDiphenhydramineTrihexyphenidylBenztropinePsychostimulantsDextroamphetamineFenfluramineMethylphenidatePemoline

No changeNo changeNo changeNo change–

––––




Other medicationsBuspironeClonidineZaleplonBarbituratesHydroxyzineZolpidemBenzodiazepinesBeta blockersNaltrexone

+++Not knownNot knownNot knownNo changeNo change–

CATIE Trial Results: CATIE Trial Results: Weight Gain Per Month Weight Gain Per Month

TreatmentTreatment

NEJM 2005 353:1209-1223

-1

0

1

2

OLZOLZ RISRIS PERPERQUETQUET ZIPZIP

Wei

gh

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(lb

) p

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lb)

per

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1-Year Weight Gain: Mean Change From Baseline Weight

Ch

ang

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m B

aseline W

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t (lb)

Weeks

Ch

ang

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rom

Bas

elin

e W

eig

ht

(kg

)

52484440363228242016128400

Olanzapine (12.5–17.5 mg)Olanzapine (all doses)QuetiapineRisperidoneZiprasidoneAripiprazole

0

5

10

15

20

25

30

0

2

4

6

8

10

12

14

Nemeroff CB. J Clin Psychiatry. 1997;58(suppl 10):45-49; Kinon BJ et al. J Clin Psychiatry. 2001;62:92-100; Brecher M et al. American College of Neuropsychopharmacology; 2004. Poster 114; Brecher M et al. Neuropsychopharmacology. 2004;29(suppl 1):S109; Geodon® [package insert]. New York, NY:Pfizer Inc; 2005. Risperdal® [package insert]. Titusville, NJ: Janssen Pharmaceutica Products, LP; 2003; Abilify® [package insert]. Princeton NJ: Bristol-Myers Squibb Company and Rockville, Md: Otsuka America Pharmaceutical, Inc.; 2005.

Diabetes Care 27(2):596-601, 2004

ADA/APA/AACE/NAASO Consensus on Antipsychotic Drugs and Obesity and Diabetes: Monitoring Protocol

Diabetes Care. 27:596-601, 2004

Start 4 wks 8 wks 12 wk qtrly 12 mos. 5 yrs.

Personal/family Hx

X X

Weight (BMI) X X X X X

Waist circumference

X X

Blood pressure X X X

Fasting glucose X X X

Fasting lipid profile

X X X X

• If a patient gains 5% of his or her initial weight at any time during therapy, one should consider switching the SGA

• For people who develop worsening glycemia or dyslipidemia while on antipsychotic therapy, the panel recommends considering switching to an SGA that has not been associated with significant weight gain and diabetes

Four American Medical Societies 2004

Treated strategy

Example1 use of clozapine associated with a 10-kg (22 l

bs) weight increase would prevent 492 suicide deaths per 100 000 patients with schizophrenia over a 10-year period.

there would be an estimated additional 416 deaths resulting from antipsychotic-induced weight gain

Early intervention2

1.Sussman N. J Clin Psychiatry 2001; 62(Suppl. 23): 5–12.2.Schwartz TL et al., obesity reviews (2004),5,233–238

Treated strategy Diet

Appetite increase by drug Prolactin promote weight gain by impairing the synt

hesis of gonadal steroids restrict the number of high-fat and high-calorie foods

Exercise Cognitive-behavioural therapy

Behaviour modification alone can generate a weight loss of 0.5–0.7 kg per week

Schwartz TL et al., obesity reviews (2004),5,233–238

Treated strategy

Pharmacotherapy shifting

Weiden P et al. Presented APA 2004.

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

Weiden P et al. Presented APA 2004. Am J Psychiatry 2005; 162:1535–1538

Change in Weight From Baseline 58 Weeks After Switch to Low Weight Gain Agent

Treated strategy Pharmacotherapy

Shifting Appetite suppressants

Sibutramine Orlistat

13 consecutive patients with psychotropic druginduced weight gain lost 34.6% 1

The average weight gained from psychotropics prior to orlistat initiation was 16.4 kg.

The average weight loss within this relatively short-time period was 5.6 kg.

1. Schwartz TL et al., Psychopharmacol Bull 2003; 37: 5–8.

Treated strategy-Pharmacotherapy

Amantadine 12 patients who had already gained a mean w

eight of 7.3 kg during olanzapine treatment amantadine at 300 mg d-1 average weight loss of 3.5 kg over 3–6 months.

Floris M et al., Eur Neuropsychopharmacol 2001; 11: 181–182.

Floris M et al., Eur Neuropsychopharmacol 2001; 11: 181–182.


Nizatidine 16-week, randomized, double-blind, placebo-

controlled study nizatidine, 300 mg bid daily 2.5 kg compared with the 5.5 kg gained by pat

ients treated without nizatidine

Breier A. et alEuropean Neuropsychopharmacology 13 (2003) 81–85

Breier A. et alEuropean Neuropsychopharmacology 13 (2003) 81–85


Naltrexone opioid antagonist, dose of 50 mg d-1 decrease weight by reversing the observed hu

nger and craving for sweet, fatty foods cause by tricyclic antidepressants and lithium.

Zimmermann U et al. Biol Psychiatry 1997; 41: 747–749


Topiramate dual purpose agent in the treatment of obese

patients with affective disorders topiramate was added on clozapine to a 29 ye

ars old male schizophrenic who had gained weight and results showed a sustained weight loss and improvement of psychotic symptoms. 1

topiramate add-on studies for bipolar disorder have shown 33–55% of patients losing weight (10–15 lbs) 2,3

1.Lessig MC. Et al., J Am Acad Child Adolesc Psychiatry 2001; 40: 1364. 2. Ghaemi SN et al., Ann Clin Psychiatry 2001; 13: 185–189.3. Vieta E et al., J Clin Psychopharmacol 2002; 22: 431–435.


Topiramate 16-week double-blind, placebo-controlled tria

l in 39 subjects, ages 10–17 olanzapine,risperidone, or quetiapine therapy Weight was stabilized in subjects receiving me

tformin, while those receiving placebo continued to gain weight (0.31 kg/week).

1.Klein DJ. Et al., Am J Psychiatry 2006; 163:2072–2079


1.Klein DJ. Et al., Am J Psychiatry 2006; 163:2072–2079


Metformine 12-week open label study 19 patients (aged 10–18 years) who had gaine

d over 10% of their baseline weight on antipsychotics

500 mg three times a day of metformin was given for in addition to psychotropic drugs

15 patients lost weight, three gained weight, and for oneweight remained unchanged.

Morrison JA, Am J Psychiatry 2002; 159: 655–657.

Real world issues Psychiatry clinic

Increasing BW associated problems BM control programs

Obesity clinic

Increase incidence on some psychiatric disorders

Impact of psychiatric disorders on obesity treatment

Recommendations

1. provide quality medical care and mental health care Screen for general health with priority for high risk conditionsOffer prevention and intervention especially for modifiable risk factors (obesity, abnormal glucose and lipid levels, high blood pressure, smoking, alcohol and drug use, etc.)Prescribers will screen, monitor and intervene for medication risk factors related to treatment of SMI (e.g. risk of metabolic syndrome with use of second generation anti-psychotics)Treatment per practice guidelines, e.g heart disease, diabetes, smoking cessation, use of novel anti-psychotics.

2. Care coordination Models

Routine sharing of clinical information with other providers (primary and specialty healthcare providers as well as mental health providersCare integration where services are co-located

Recommendations

3. Support consumer wellness and empowerment to improve personal mental and physical well-being

educate / share information to make healthy choices regarding nutrition, tobacco use, exercise, implications of psychotropic drugsteach /support wellness self-management skillsteach /support decision making skillsmotivational interviewing techniquesImplement a physical health Wellness approach that is consistent with Recovery principles, including supports for smoking cessation, good nutrition, physical activity and healthy weight.attend to cultural needs

Recommendations

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Obesity treated strategy and clinical practice in psychiatric disease related obesity 中國醫藥大學附設醫院 精神醫學部 黃介良 psyche@

Obesity treated strategy and clinical practice in psychiatric disease related obesity 中國醫藥大學附設醫院精神醫學部黃介良 psyche@