Obesity treated strategy and clinical practice in psychiatric disease related obesity

1
Obesity treated strategy and clinical practice in
psychiatric disease related obesity

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• psyche_at_www.cmuh.org.tw

2
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

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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,
2005 2. Onyike CU et al., Am J Epidemiol
200315811391147
4
Psychiatric illness related Obesity bipolar
affective disorder

• Patients with bipolar disorder appear to be at
  greater risk than the general population for
  overweight and obesity 1,2
• Risk factor1
• Comorbid binge-eating disorder
• the number of depressive episodes
• treatment with medications associated with weight
  gain
• alone or in combination excessive carbohydrate
  consumption
• low rates of exercise

1.Keck PE et al.,J Clin Psychiatry. 2003
Dec64(12)1426-35. 2. McElroy SL et al.,J Clin
Psychiatry. 2002 Mar63(3)207-13.
5
BMI Distributions for General Population and
Those With Schizophrenia (1989)
30
Under-weight
Obese
Overweight
Acceptable
20
Percent
10
0
lt 18.5
18.5-20
20-22
22-24
24-26
26-28
28-30
30-32
32-34
gt 34
BMI Range
No schizophrenia Schizophrenia
Allison DB et al. J Clin Psychiatry.
199960215-220.
6
Psychiatric illness related ObesityCause

• Disease itself
• Lifestyle
• Psychotropic effect

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

7
Psychiatric illness in Obesity population

• Obesity (BMIgt30)
• 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. 200663824-8
30
8
Simon GEet al., Arch Gen Psychiatry. 200663824-8
30
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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.
200090251257
10
Diabetes and Obesity The Continuing Epidemic
Diabetes
Mean body weight
kg
Prevalence ()
Year
Mokdad et al. Diabetes Care. 2000231278. Mokdad
et al. JAMA. 19992821519. Mokdad et al. JAMA.
20012861195.
11
Cardiovascular Disease (CVD) Risk Factors
Modifiable Risk Factors Estimated Prevalence and Relative Risk (RR) Estimated Prevalence and Relative Risk (RR) Estimated Prevalence and Relative Risk (RR) Estimated Prevalence and Relative Risk (RR)
Modifiable Risk Factors Schizophrenia Schizophrenia Bipolar Disorder Bipolar Disorder
Obesity 4555, 1.5-2X RR1 265
Smoking 5080, 2-3X RR2 556
Diabetes 1014, 2X RR3 107
Hypertension 184 155
Dyslipidemia Up to 5X RR8
1. Davidson S, et al. Aust N Z J Psychiatry.
200135196-202. 2. Allison DB, et al. J Clin
Psychiatry. 1999 60215-220. 3. Dixon L, et al.
J Nerv Ment Dis. 1999187496-502. 4. Herran A,
et al. Schizophr Res. 200041373-381. 5. MeElroy
SL, et al. J Clin Psychiatry. 200263207-213. 6.
Ucok A, et al. Psychiatry Clin Neurosci.
200458434-437. 7. Cassidy F, et al. Am J
Psychiatry. 19991561417-1420. 8. Allebeck.
Schizophr Bull. 199915(1)81-89.
12
Psychiatric illness related ObesityCause

• Disease itself
• Lifestyle
• Psychotropic effect

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

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Body Weight Changes AssociatedWith
Psychopharmacology
Malhi GS, Australian and New Zealand Journal of
Psychiatry 2001 35315321
14
Body Weight Changes AssociatedWith
Psychopharmacology-1
Medication Effect on Weight
Antipsychotic drugs Chlorpromazine Thioridazine Fluphenazine Haloperidol Perphenazine Pimozide Loxapine Molindone Clozapine Olanzapine Quetiapine Risperidone Ziprasidone Not clear
Vanina Y. Psychiatric Services 53842847, 2002
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Body Weight Changes AssociatedWith
Psychopharmacology-2
Medication Effect on Weight
Mood stabilizers Valproate products Lithium Carbamazepine Gabapentin Lamotrigine Topiramate Not clear
Vanina Y. Psychiatric Services 53842847, 2002
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Body Weight Changes AssociatedWith
Psychopharmacology-3
Medication Effect on Weight
Antidepressant drugs-1 Amitriptyline Imipramine Nortriptyline Protriptyline Trimipramine Desipramine Phenelzine Tranylcypromine Isocarboxazid Not clear Not clear Not clear No change No change
Vanina Y. Psychiatric Services 53842847, 2002
17
Body Weight Changes AssociatedWith
Psychopharmacology-4
Medication Effect on Weight
Antidepressant drugs-2 Mirtazapine Citalopram Fluoxetine Sertraline Trazodone Fluvoxamine Paroxetine Venlafaxine Bupropion Nefazodone Not clear Not clear Not clear Not clear Not known Not known No change
Vanina Y. Psychiatric Services 53842847, 2002
18
Body Weight Changes AssociatedWith
Psychopharmacology-5
Medication Effect on Weight
Antiparkinsonian drugs Amantadine Biperidine Diphenhydramine Trihexyphenidyl Benztropine Psychostimulants Dextroamphetamine Fenfluramine Methylphenidate Pemoline No change No change No change No change
Vanina Y. Psychiatric Services 53842847, 2002
19
Body Weight Changes AssociatedWith
Psychopharmacology-6
Medication Effect on Weight
Other medications Buspirone Clonidine Zaleplon Barbiturates Hydroxyzine Zolpidem Benzodiazepines Beta blockers Naltrexone Not known Not known Not known No change No change
Vanina Y. Psychiatric Services 53842847, 2002
20
CATIE Trial Results Weight Gain Per Month
Treatment
Weight gain (lb) per month
OLZ
RIS
PER
QUET
ZIP
NEJM 2005 3531209-1223
21
1-Year Weight Gain Mean Change From Baseline
Weight
14
30
12
25
10
20
Change From Baseline Weight (kg)
8
15
Change From Baseline Weight (lb)
6
10
4
5
2
0
0
52
48
44
40
36
32
28
24
20
16
12
8
4
0
0
Weeks
Nemeroff CB. J Clin Psychiatry. 199758(suppl
10)45-49 Kinon BJ et al. J Clin Psychiatry.
20016292-100 Brecher M et al. American College
of Neuropsychopharmacology 2004. Poster 114
Brecher M et al. Neuropsychopharmacology.
200429(suppl 1)S109 Geodon package insert.
New York, NYPfizer 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.
22
Diabetes Care 27(2)596-601, 2004
23
Consensus Conference on Antipsychotic Drugs and
Risk of Obesity and Diabetes
Drug Weight Gain Diabetes Risk Dyslipidemia
clozapine
olanzapine
risperidone D D
quetiapine D D
aripiprazole /- - -
ziprasidone /- - -
increased effect - no effect D
discrepant results.
American Diabetes Association, American
Psychiatric Association, American Association of
Clinical Endocrinologists, North American
Association for the Study of Obesity
Diabetes Care 27596-601, 2004
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ADA/APA/AACE/NAASO Consensus on Antipsychotic
Drugs and Obesity and Diabetes Monitoring
Protocol
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
Diabetes Care. 27596-601, 2004
25

• 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

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Treated strategy

• Example1
• use of clozapine associated with a 10-kg (22 lbs)
  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) 512. 2.Schwartz TL et al., obesity reviews
(2004),5,233238
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Treated strategy

• Diet
• Appetite increase by drug
• Prolactin promote weight gain by impairing the
  synthesis 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 0.50.7 kg per week

Schwartz TL et al., obesity reviews
(2004),5,233238
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Treated strategy

• Pharmacotherapy
• shifting

Weiden P et al. Presented APA 2004.
29
Change in Weight From Baseline 58 Weeks After
Switch to Low Weight Gain Agent
58
27
19
49
53
45
40
36
32
23
14
10
6
5
0


-5
LS Mean Change (lb)

-10


-15
Plt0.05 Plt0.01 Plt0.0001
-20

-25
Switched from
Conventionals
Risperidone
Olanzapine
Weiden P et al. Presented APA 2004. Am J
Psychiatry 2005 16215351538
30
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 58.
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Treated strategy-Pharmacotherapy

• Amantadine
• 12 patients who had already gained a mean weight
  of 7.3 kg during olanzapine treatment
• amantadine at 300 mg d-1
• average weight loss of 3.5 kg over 36 months.

Floris M et al., Eur Neuropsychopharmacol 2001
11 181182.
32
Floris M et al., Eur Neuropsychopharmacol 2001
11 181182.
33
Treated strategy-Pharmacotherapy

• 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
  patients treated without nizatidine

Breier A. et alEuropean Neuropsychopharmacology
13 (2003) 8185
34
Breier A. et alEuropean Neuropsychopharmacology
13 (2003) 8185
35
Treated strategy-Pharmacotherapy

• Naltrexone
• opioid antagonist, dose of 50 mg d-1
• decrease weight by reversing the observed hunger
  and craving for sweet, fatty foods cause by
  tricyclic antidepressants and lithium.

Zimmermann U et al. Biol Psychiatry 1997 41
747749
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Treated strategy-Pharmacotherapy

• Topiramate
• dual purpose agent in the treatment of obese
  patients with affective disorders
• topiramate was added on clozapine to a 29 years
  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 3355 of patients losing weight
  (1015 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 185189. 3. Vieta E
et al., J Clin Psychopharmacol 2002 22 431435.
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Treated strategy-Pharmacotherapy

• Topiramate
• 16-week double-blind, placebo-controlled trial in
  39 subjects, ages 1017
• olanzapine,risperidone, or quetiapine therapy
• Weight was stabilized in subjects receiving
  metformin, while those receiving placebo
  continued to gain weight (0.31 kg/week).

1.Klein DJ. Et al., Am J Psychiatry 2006
16320722079
38
Treated strategy-Pharmacotherapy
1.Klein DJ. Et al., Am J Psychiatry 2006
16320722079
39
Treated strategy-Pharmacotherapy

• Metformine
• 12-week open label study
• 19 patients (aged 1018 years) who had gained
  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 655657.
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Disparities in care impact of mental illness on
diabetes management
Depression
Anxiety
Psychosis
Mania
Substance use disorder
Personality disorder
0.8
1.0
1.2
1.4
1.6
0.8
1.0
1.2
1.4
1.6
0.8
1.0
1.2
1.4
1.6
0.8
1.0
1.2
1.4
1.6
0.8
1.0
1.2
1.4
1.6
0.8
1.0
1.2
1.4
1.6
No HbA test done
No LDL test done
No Eye examination done
No Monitoring
Poor glycemic control
Poor lipemic control
Odds ratio for
313,586 Veteran Health Authority patients with
diabetes76,799 (25) had mental health
conditions (1999)
Frayne et al. Arch Intern Med. 20051652631-2638
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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

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Recommendations

• provide quality medical care and mental health
  care
• Screen for general health with priority for high
  risk conditions
• Offer 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.

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Recommendations

• 2. Care coordination Models
• Routine sharing of clinical information with
  other providers (primary and specialty healthcare
  providers as well as mental health providers
• Care integration where services are co-located

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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 drugs
• teach /support wellness self-management skills
• teach /support decision making skills
• motivational interviewing techniques
• Implement 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

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• Thank you for your attention
• Questions or Comments?