Metabolic syndrome in psychiatric patients: An update

19th March 2012

Presenter : Shanooha Mansoor Supervisor: Dr. Wan Norhairda Wan Abdullah

definition
Cluster of clinical & lab abnormalities:

Abdominal ( central) obesity Insulin resistance Hypertension Dyslipidemia :

Low levels of HDL cholesterol High levels of TG

Microalbuminuria ( WHO)

Criteria for dx

WHO

International Diabetes Federation ( IDF) National Cholesterol Education Project Adult Treatment Panel ( NCEPATP III) Joint statement ADA,EASD concluded MS is imprecisely defined:

Recommended to t/t all CVD risks whether they fulfill criteria for MS or not

Diagnostic criteria :
BP WHO * (1999) Central Obesity Glucose abnoma DM / IGT IFG/ Insulin resistance Dyslipidemia TG > 150 mg/dl ( 1.7 mmol/l) HDL : <35 mg/dl ( male) <39 mg/dl ( female) TG>150mg/dl HDL: <40 mg /dl (male) <50mg/dl (female) >140/90Waist-hip ratio : > 0.9 ( male) > 0.8 ( female)

IDF (2006 >130/85 - Central / rx ob + 2 others

Waist circumference: >94 cm male >80 cm female

FPG > 100mg.dl/5. 6 mmol/l DM II

NCEP>130/80 Waist cir: FBS > 110 Same as IDF ATP: >40 inc ( male) mg% < 126 =/> * microalbuminuria: albumin/creatinine ratio: 3 >35 inc (female) mg%

Diagnostic criteria :

Linked metabolic abnormalities:

Impaired glucose handling/insulin resistance Atherogenic dyslipidemia Endothelial dysfunction Prothorombotic state Hemodynamic changes Proinflammatory state Excessive ovarian testesterone production

Resulting clinical conditions

Type 2 DM :

Every 1% raise HbA1c18% raise in CVD Goal : FBS 90-130, PPBS: <180 , HbA1c<7

Essential HTN PCOS Non-alcoholic fatty liver disease Sleep apnea

Prevalence

Psychiatric patients :
Prevalence 1.5-2 x higher than gen pop

Sedentary life style Poor food intake Substance abuse & smoking

Limited data on antipsychotic nave patients:

Small cohort: visceral fat content 3X higher Increased prevalence of impaired fasting glucose, insulin resistant, higher plasma glucose level, insulin & cortisol

Prevalence

Correl et al 2007

Risk Factors

Increased body weight/ large waist circum* postmenopausal status Increased age male smoking high carbohydrate diet physical inactivity atypical antipsychotic medications,

Antipsychotic medication & antidepressants

SGAs associated with weight gain & dyslipidemia

Olanzapine, Clozapine : Inc cholesterol correlated with weight

Significant correlation seen amongst bipoar d/o and schizophrenia patients on SGAs

Antipsychotic and weight gain : Metaanalysis Allison et al

Percentage of patients who presented with >7% of weight gain : CATIE study

Mean wt gain 0.9 kg Over 1 mth

0.2 kg

0.2 kg

-0.1 kg

-0.1 kg

Antidepressants & mood stabilizers

TCA: weight gain, insulin resistance, increased cholesterol SRI : increase in weight on long term rx lithium : long term : > 10kgs in 20% of patients Valporic acid: similar to lithium CBZ: lower Valporic acid 71 % vs 43% CBZ weight gain > 5% ( corman et al)

C u Consensus development conference on r APAs, Obesity & Diabetes ( 2003) r e n t u s e o f

Relationship b/w SGAs and incidence of obesity & DM Obesity:

rapid increase in weight : 1st few months , does not plateau after 1 year 10 weeks therapy, avg weight gain 0.5-5.0 kg Mzm unknown:

R-r profile maybe responsible:

Antagonism of msucarinic r.r :weight gain hunger & satiety maybe altered, binding affinities to serotonin, NE, dopamine, H1 r-r*

Weight gain account for MS

Diabetes

Onset or exacerbation including hyperglycemic crises Usually at onset of rx Hyperglycemia resolved on discontinuation in several cases, reappeared on rechallenging Olanzapine and clozapine Mzm:

Insulin resistance: due to weight gain or change in body fat distribution Direct effect of insulin sensitive target tissues

Weight gain Clozapine Olanzapine Risperidone Quetiapine Aripiprazole* Ziprasidone* +++ +++ ++ ++ +/+/-

Risk of DM + + d d -

Worsening LP + + d d -

Risk-Benefit Assessment

Factors to be considered in choosing APAs

Nature of condition Specific target symptoms Past history of drug response, effectiveness, adherence Patient preference, availabilities of formulations Cormorbidities ( other medication) Need for monitoring

Monitoring

Monitoring

Encouraged to monitor own weight Nutrition and physical activity Awareness of symptoms, esp acute states such as DKA, immediate referral if > 300mg/di

Management Tips for those on APAs

Refer patients with abnormal glucose or lipid levels for medical consultation Encourage weight loss: modest weight loss can have health benefits Be alert to the possibility of DKA, especially in diabetic patients newly begun on atypical antipsychotics

Management Tips for those on APAs Leverage your therapeutic rapport to

establish moderate exercise and discourage smoking whenever possible

Consider discontinuing or switching antipsychotic: may resolve hyperglycemia and diabetes in some cases Switch if :

Weight gain >5% ( ADA-APA guideline) Hyperglycemia

Four strategies for switching

Cross tapering* Starting new medication at therapeutic dose while tapering old one off Stopping older antipsychotic abruptly while starting new one gradually Starting new drug at therapeutic dose and stopping old one abruptly

Lifestyle modification:

Nutritional intervention : reduce fat chol, inc fiber Exercise:

Improves CV fitness, wt control

sensitivity to insulin Weight loss

Goal : brisk walking 30 min/day 10% reduction in body weight Modest weight loss increased life

Medication

HTN:

ACE inhibitors, ARBs Thiazides, calcium channel/alpha/beta blockers

Hyperlipidemia:

Statins, fibrates

Platelet inhibitors:

DM:

Insulin sensitizers:

Biguanides: Metformin* : reverse weight gain and metabolic disturbance due to olanzapine PPAR agnoists: Glitazones, Glitazars Sulfonylureas: glipizide, glyburide,glimparide,gliblencamide Meglitinides: repaglanide,netiglamide

Insulin Secretagogues:

Insluin:

Food for thought

Vitamin B (specifically folate) supplement may help ameliorate metabolic effects of the AAP (Elligrod et al) Topiramate: off label to counteract weight gain : recent double blind trail show it can prevent APA induced adverse metabolic effects ( Afshar H et al) Amantadine: promote weight loss in patients on APA with no influence on psychopathology ( Deberdt W et al)

Prevention:

Education: patient and caregiver Screening & reduction Blood sugar?HbA1c Lipids : 10% leads to 30% reduction in CVD risk BP: lowering 4-6% leads 15% decrease in CVD risk Smoking : cessation 50-70% lowering of CVD prev Body habitus : BMI < 25, lowers CVD 3555% Central obesity reduction * 46% can

Cochrane Systemic Review:

Evaluate effects of risperidone compared with other atypical antipsychotics for people with schizophrenia & schizophrenia-like psychosis ( Katja et al 2011) Risperidone:

weight gain > amisulpiride < Olanzapine & clozapine Cholesterol > aripiprizole < Ziprasidone

Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems ( Mukundan et al 2010)

switching to aripiprazole / quetiapine from olanzapine

Weight loss 1.94kg Decrease in BMI Significant decrease in FBS

Less likely to leave if on olanzapine * No significant outcome on those switched and

Prediction of long term effects of olanzapine and risperidone from baseline BMI in schizophrenia and bipolar d/o W.V Bobo et al 2011 Higher baseline BMI : avg glycemic changes after 12 months with OLZ, Risp Normal baseline BMI maybe more susceptible to OLZ induced hyperlipidosis

Local study:

MS in psychiatric patients with primary psychotic and mood disorders :Abdul

Hamid Abdul Rahman et al 2009

Prevalance of MS : 37.2% Higher amongst mood disorder patients MS not associated with anti psychotic therapy (P 0.41)

Adherence to metabolic monitoring guidelines in atypical antipsychotic treated subjects: Do physicians comply ? Jesjeet Gill et al 2011

Data on metabolic monitoring collected over an year Recommended tests/procedures : performed in less than 50%

Summary

General population also at risk of MS SMI patients more vulnerable Routine screening SGAs associated with more weight gain : esp clozapine, olanzapine, quetiapine and lesser extent risperidone

Vigilant for metabolic issues and intervene early whe appropriate Interventions:

Nutritional counselling Exercise Medication

I hear and I forget I see and I remember I do and I understand Confucius

References

American Psychiatric Association: Practice Guideline for the Treatment of Patients With Schizophrenia, 2nd ed. Am J Psychiatry 2004; 161(2 suppl) Stahl S. The metabolic syndrome: psychopharmacologists should weigh the evidence for weighing the patient [BRAINSTORMS]. J Clin Psychiatry 2002;63:10941095 Ellingrod, V., Taylor, S, et-al, Risk Factors Associated With Metabolic Syndrome in Bipolar and Schizophrenia Subjects Treated With Antipsychotics: The Role of Folate Pharmacogenetics, Journal of Clinical Psychopharmacology: 2012, 32 (2) 261265
Coxtall, JD., Aripiprazole: a review of its use in the management of schizophrenia in adults. CNS Drugs. 2012 Feb 1;26(2):155-83. Metabolic syndrome: relevance to antidepressant treatment : Pratap et al 2006 Metabolic issues in patients with SMI : Leslie et al 2005

Lowest risk for antidepress Discuss management of MS Polypharmacy MS