# Presentation: 343147

## Objectives

- Define the metabolic syndrome
- Describe prevalence of metabolic changes with second generation antipsychotics in VA
- Discuss strategies for monitoring
- Describe challenges & treatment options for managing patients who develop metabolic changes

## Metabolic Syndrome Markers

|      Risk Factors |        Defining Level |
| --- | --- |
| Triglyceride | > 150 mg/dL |
| HDL-cholesterol
Men
Women | 
< 40 mg/dL
< 50 mg/dL |
| Blood Pressure | > 130/> 85 mm Hg |
| Fasting Glucose | > 110 mg/dL |
| Waist Circumference
Men
Women | 
>102 cm (> 40 in)
> 88 cm (> 35 in) |
| Substituted BMI (WHO) | > 30 kg/m2 |

## First Generation Antipsychotics

- Extrapyramidal side effects and Tardive Dyskinesia

**Second Generation Antipsychotics**

- Metabolic side effects

## Atypical Antipsychotic Agents

- Clozapine (Clozaril®)
- Risperidone (Risperdal®)
- Olanzapine (Zyprexa®)
- Quetiapine (Seroquel®)
- Ziprasidone (Geodon®)
- Aripiprazole (Abilify®)

## Short-Term Studies: Weight Gain

**Tandon et al. J Ser Res. 1997;4:159-177**

**Percentage of Patients with ******** 7% Weight Gain**

## Long-Term Studies: Weight Gain

- Clozapine-treated patients:
- Gained more than 40 lbs
- More than 30% of patients gained 10% or more of their initial body weight
- Long-term data:
- 56% of patients on olanzapine gained more than 7% of their body weight

**Psychiatric Clinic North Am 2003; 26(1):165-90.**

## Hyperglycemia/Diabetes

- Clozapine & olanzapine – numerous reports
- Risperidone & quetiapine-         few reports

**J Clin Psychiatry 1999;60:783-791**
**Psychosomatics 1999;40:438-443**
**Psychiatric Clinic North Am. 2003; 26(1):165-90**

## Dyslipidemias

- Retrospective study: clozapine ↑ TGs
- 48% (184 to 273mg/dL) in men
- 35% (165 to 223 mg dL)  in women
- Case series: TGs
- ↑ 37% (162 to 222 mg/dl)

**Psychiatric Clinic North Am. 2003; 26(1):165-90**
**Am J Psychiatry 1999;156:14714-1472.**
**Am J Psychiatry  1999;156(8): 1270-1272.**

## Weight Gain, Diabetes, and Dyslipidemias

- Atypical Antipsychotic Agents
- Clozapine > Olanzapine > Quetiapine
- Risperidone > Ziprasidone = Aripiprazole

## Atypical Antipsychotic Agents

- FDA mandates changes in labeling in 2004
**Warnings for hyperglycemia and diabetes**
**Affects all atypical antipsychotics**
- Consensus Development Conference on Antipsychotic Drugs & Obesity & Diabetes
**Aripiprazole and ziprasidone **
**Little/no weight gain**
**Little/no diabetes**
**Little/no dyslipidemia**

**Diabetes Care 2004; 27:596-601.**

## Clinical Data Warehouse

## Slide 12

## Demographics

|  | Number in Group | Average Age | Gender 
(% Male) |
| --- | --- | --- | --- |
| Population Group |  |  |  |
| Treatment Group |  |  |  |

**106,729             66.5              95%**

**5,808               57.4              93%**

## VISN-21 Regional Findings

- Population Group

- 2nd Generation Antipsychotic Treatment Group

- Chi squared = 18.5, df =1

- Chi

- Chi Squared = 68.7, df = 1

## VISN-21 Regional Findings

- Prevalence (%) Diabetes by Age

- Treatment Group

- Population Group

**VISN-21 Regional Findings**

**p=0.009**

## VISN-21 Regional Findings

- Treatment Group

- Population Group

- Prevalence (%) Metabolic Syndrome by Age

**p<0.001**

**p<0.001**

**p<0.001**

## VISN-21 Regional Findings

**Prevalence of Diabetes in Patients on**
**Second Generation Antipsychotics by Individual Drug**

**28%**

## VISN-21 Regional Findings

**Prevalence of Metabolic Syndrome in Patients on**
**Second Generation Antipsychotics by Individual Drug**

**39%**

## Slide 19

## VA Sierra NV- Local Findings

|  | All AAs | Olanzapine | Quetiapine | Risperidone |
| --- | --- | --- | --- | --- |
| Total # pts | 105 | 45 | 40 | 20 |
| Developed 
Metabolic
Syndrome | 31 (29.5%)* | 12 (26.7%)* | 13 (32.5%)* | 6 
(30%)* |
| Developed 
Metabolic Syndrome
still on antipsychotic 
N (%) | 15 (48%) | 5 (42%) | 7 (54%) | 3 (50%) |

*** Wilcox signed rank p < 0.001**

## American DiabetesAssociation Recommendations

- Personal/family Hx – BL, annually
- Weight (BMI) – BL, 4 wks, 8 wks, 12 wks, quarterly
- Waist circumference – BL, annually
- Blood Pressure – BL, 12 wks, annually
- Fasting plasma glucose – BL, 12 wks, annually
- Fasting lipid profile – BL, 12 wks, generally every 5 years

## VISN-21 Regional Findings

- Atypical Antipsychotics: By Indication

- Psychosis and other appropriate indications

- PTSD
- (Off Label)

- Other Bipolar
- (Off Label)

- Other Use
- (Off Label)

- Schizophrenia

## Metabolic Syndrome Report

- Left side

- Right side

## Recommendations for Monitoring 

- Patient education and behavior modification
- Monitor weight changes
- Obtain Labs

**Psychiatric Clinic North Am. 2003; 26(1):165-90.**

## VANTS CallJune 29, 20052:00 PM ET1-800-767-1750Access code: 95744#