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At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?
This article answers those questions by addressing:
- clinical guidelines for diagnosing metabolic syndrome
- suggested intervals for monitoring at-risk patients
- strategies for managing metabolic abnormalities with lifestyle changes or medication.
CASE REPORT: 'FAT' AND FRUSTRATED
Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.
Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.
Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.
The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).
The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.
Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?
IMPLICATIONS OF METABOLIC SYNDROME
Patients with metabolic syndrome are at increased risk for:
In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.
DEFINING METABOLIC SYNDROME
Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.
According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:
- abdominal obesity
- insulin resistance
- high blood pressure
- elevated triglycerides
- below-normal HDL.
This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.
Table 1
5 defined risk factors* for metabolic syndrome
| Risk factor | Clinically significant level |
|---|---|
| Abdominal obesity | |
| Men | Waist circumference >40 in (102 cm) |
| Women | Waist circumference >35 in (88 cm) |
| Blood pressure | |
| Systolic | >130 mm Hg |
| Diastolic | >85 mm Hg |
| HDL count | |
| Men | <40 mg/dL (<1.04 mmol/L) |
| Women | <50 mg/dL (<1.30 mmol/L) |
| Fasting glucose | |
| Men, women | >110 mg/dL (>6.11 mmol/L) |
| Triglycerides | |
| Men, women | >150 mg/dL (>1.70 mmol/L) |
| * If 3 risk factors are present, suspect metabolic syndrome | |
| HDL: high-density lipoprotein cholesterol | |
| Source: Adapted from reference 5. | |
MONITORING FREQUENCY
Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6
Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).
Table 2
Suggested monitoring intervals for patients taking atypical antipsychotics*
| Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually | Every 5 years | |
|---|---|---|---|---|---|---|---|
| Personal/family history | X | X | |||||
| Weight (BMI) | X | X | X | X | X | ||
| Waist circumference | X | X | |||||
| Blood pressure | X | X | X | ||||
| Fasting plasma glucose | X | X | X | ||||
| Fasting lipid profile | X | X | X | ||||
| *Clinical status may warrant more-frequent assessments | |||||||
| BMI: Body mass index | |||||||
| Source: Reference 6. | |||||||
MANAGING METABOLIC PROBLEMS
Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:
- weight management, weight control education, and promoting regular exercise and a healthy diet
- switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
- working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.
Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.
Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7
Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.
Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19
In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.
Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:
- 43% had lower triglycerides than at baseline
- 16% had higher HDL cholesterol
- 38% had lower blood pressure
- 9% had improved fasting glucose
- 28% reduced their waist circumference.
Table 3
Interventions for specific metabolic complications
| Metabolic complication | Nondrug interventions8 | Medications |
|---|---|---|
| Abdominal obesity | Encourage weight loss | Sibutramine*† |
| Increase physical activity | Appetite suppressant | |
| Orlistat*† | ||
| Lipase inhibitor | ||
| Hypertriglyceridemia | Encourage weight loss | Fibrates9* |
| Increase physical activity | Reduce fasting and postprandial triglycerides 20% to 50% | |
| Increase low-glycemic-index food intake | Shift small dense LDL to large buoyant particles | |
| Reduce total carbohydrate intake | Increase HDL particles 10% to 35% | |
| Increase consumption of omega-3 fatty acids | Nicotinic acid10 | |
| Limit alcohol consumption | Reduces triglycerides 20% to 50% | |
| Statins11 | ||
| Reduce fasting and postprandial triglycerides 7% to 30% | ||
| Reduce LDL particles | ||
| Increase HDL particles | ||
| Reduce major coronary vascular events | ||
| Low HDL | Encourage weight loss | Nicotinic acid* |
| Increase physical activity | Increases HDL particles 15% to 35% | |
| Stop smoking | Fibrates9 | |
| Increase monounsaturated fat intake | See above | |
| Statins11 | ||
| See above | ||
| Hypertension | Encourage weight loss | ACE inhibitors* |
| Increase physical activity | May slow progression to diabetes12 | |
| Reduce saturated fat intake | Decrease CVD events13 | |
| Reduce sodium intake | Delay progression of microalbuminuria13 | |
| Limit alcohol consumption | Angiotensin receptor blockers | |
| May improve dyslipidemia associated with metabolic syndrome14 | ||
| Delay progression of microalbuminuria13 | ||
| Hyperglycemia | Encourage weight loss | Metformin,* thiazolidinediones |
| Increase physical activity | Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15 | |
| Reduce total carbohydrates | ||
| * Suggested first-line therapy. | ||
| † For patients with BMI 30 kg/m2 | ||
| ACE: Angiotensin-converting enzyme | ||
| CVD: Cardiovascular disease | ||
| HDL: High-density lipoprotein cholesterol | ||
| LDL: Low-density lipoprotein cholesterol | ||
Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.
By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21
In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22
Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).
Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.
Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6
Table 4
Atypical antipsychotics and their propensity for causing metabolic abnormalities
| Drug | Weight gain | Hyperglycemia | Dyslipidemia |
|---|---|---|---|
| Clozapine | High | High | High |
| Olanzapine | High | High | High |
| Risperidone | Medium | Medium | Low |
| Quetiapine | Medium | Medium | High |
| Aripiprazole | Low | Low | Low |
| Ziprasidone | Low | Low | Low |
| Source: Reference 6 | |||
Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).
Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).
CASE CONTINUED: 10 LBS IN 10 WEEKS
At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).
Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.
Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.
- National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
- Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
- National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
- Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.
Drug brand names
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sibutramine • Meridia
- Ziprasidone • Geodon
Disclosure
Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.
1. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715-22.
2. Isomma B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.
3. Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998;148:958-66.
4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
5. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
6. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.
7. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998;6(suppl 2):51S-209S.
8. Darwin D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875-82.
9. Maki KC. Fibrates for treatment of the metabolic syndrome. Curr Atheroscler Rep 2004;6:45-51.
10. Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-85.
11. Showers JR. Effects of statins on the vasculature: implications for aggressive lipid management in the cardiovascular metabolic syndrome. Am J Cardiol 2003;91(suppl):14B-22B.
12. Yusuf S, Gerstein H, Hoogwerf B, et al. for the HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001;286:1882-5.
13. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.
14. Derosa G, Cicero AF, Bertone G, et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized double-blind study. Clin Ther 2004;26:1228-36.
15. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
16. Buchanan T, Xiang A, Peters R, et al. Prevention of type 2 diabetes by treatment of insulin resistance: comparison of early vs. late in the TRIPOD study [abstract]. Diabetes 2002;51(suppl 2):A35.-
17. Leon AS, Sanchez O. Meta-analysis of the effects of aerobic exercise training on blood lipids. Circulation 2001;104(suppl II):414-15 (abstract).
18. Fagard RH. Exercise characteristics and blood pressure response to dynamic physical training. Med Sci Sports Exerc 2001;33(6 suppl):S484-S492.
19. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33(6 suppl):S438-S445.
20. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 2003;35:1703-9.
21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.
22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.
23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.
24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.
25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.
At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?
This article answers those questions by addressing:
- clinical guidelines for diagnosing metabolic syndrome
- suggested intervals for monitoring at-risk patients
- strategies for managing metabolic abnormalities with lifestyle changes or medication.
CASE REPORT: 'FAT' AND FRUSTRATED
Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.
Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.
Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.
The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).
The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.
Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?
IMPLICATIONS OF METABOLIC SYNDROME
Patients with metabolic syndrome are at increased risk for:
In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.
DEFINING METABOLIC SYNDROME
Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.
According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:
- abdominal obesity
- insulin resistance
- high blood pressure
- elevated triglycerides
- below-normal HDL.
This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.
Table 1
5 defined risk factors* for metabolic syndrome
| Risk factor | Clinically significant level |
|---|---|
| Abdominal obesity | |
| Men | Waist circumference >40 in (102 cm) |
| Women | Waist circumference >35 in (88 cm) |
| Blood pressure | |
| Systolic | >130 mm Hg |
| Diastolic | >85 mm Hg |
| HDL count | |
| Men | <40 mg/dL (<1.04 mmol/L) |
| Women | <50 mg/dL (<1.30 mmol/L) |
| Fasting glucose | |
| Men, women | >110 mg/dL (>6.11 mmol/L) |
| Triglycerides | |
| Men, women | >150 mg/dL (>1.70 mmol/L) |
| * If 3 risk factors are present, suspect metabolic syndrome | |
| HDL: high-density lipoprotein cholesterol | |
| Source: Adapted from reference 5. | |
MONITORING FREQUENCY
Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6
Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).
Table 2
Suggested monitoring intervals for patients taking atypical antipsychotics*
| Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually | Every 5 years | |
|---|---|---|---|---|---|---|---|
| Personal/family history | X | X | |||||
| Weight (BMI) | X | X | X | X | X | ||
| Waist circumference | X | X | |||||
| Blood pressure | X | X | X | ||||
| Fasting plasma glucose | X | X | X | ||||
| Fasting lipid profile | X | X | X | ||||
| *Clinical status may warrant more-frequent assessments | |||||||
| BMI: Body mass index | |||||||
| Source: Reference 6. | |||||||
MANAGING METABOLIC PROBLEMS
Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:
- weight management, weight control education, and promoting regular exercise and a healthy diet
- switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
- working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.
Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.
Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7
Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.
Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19
In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.
Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:
- 43% had lower triglycerides than at baseline
- 16% had higher HDL cholesterol
- 38% had lower blood pressure
- 9% had improved fasting glucose
- 28% reduced their waist circumference.
Table 3
Interventions for specific metabolic complications
| Metabolic complication | Nondrug interventions8 | Medications |
|---|---|---|
| Abdominal obesity | Encourage weight loss | Sibutramine*† |
| Increase physical activity | Appetite suppressant | |
| Orlistat*† | ||
| Lipase inhibitor | ||
| Hypertriglyceridemia | Encourage weight loss | Fibrates9* |
| Increase physical activity | Reduce fasting and postprandial triglycerides 20% to 50% | |
| Increase low-glycemic-index food intake | Shift small dense LDL to large buoyant particles | |
| Reduce total carbohydrate intake | Increase HDL particles 10% to 35% | |
| Increase consumption of omega-3 fatty acids | Nicotinic acid10 | |
| Limit alcohol consumption | Reduces triglycerides 20% to 50% | |
| Statins11 | ||
| Reduce fasting and postprandial triglycerides 7% to 30% | ||
| Reduce LDL particles | ||
| Increase HDL particles | ||
| Reduce major coronary vascular events | ||
| Low HDL | Encourage weight loss | Nicotinic acid* |
| Increase physical activity | Increases HDL particles 15% to 35% | |
| Stop smoking | Fibrates9 | |
| Increase monounsaturated fat intake | See above | |
| Statins11 | ||
| See above | ||
| Hypertension | Encourage weight loss | ACE inhibitors* |
| Increase physical activity | May slow progression to diabetes12 | |
| Reduce saturated fat intake | Decrease CVD events13 | |
| Reduce sodium intake | Delay progression of microalbuminuria13 | |
| Limit alcohol consumption | Angiotensin receptor blockers | |
| May improve dyslipidemia associated with metabolic syndrome14 | ||
| Delay progression of microalbuminuria13 | ||
| Hyperglycemia | Encourage weight loss | Metformin,* thiazolidinediones |
| Increase physical activity | Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15 | |
| Reduce total carbohydrates | ||
| * Suggested first-line therapy. | ||
| † For patients with BMI 30 kg/m2 | ||
| ACE: Angiotensin-converting enzyme | ||
| CVD: Cardiovascular disease | ||
| HDL: High-density lipoprotein cholesterol | ||
| LDL: Low-density lipoprotein cholesterol | ||
Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.
By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21
In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22
Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).
Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.
Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6
Table 4
Atypical antipsychotics and their propensity for causing metabolic abnormalities
| Drug | Weight gain | Hyperglycemia | Dyslipidemia |
|---|---|---|---|
| Clozapine | High | High | High |
| Olanzapine | High | High | High |
| Risperidone | Medium | Medium | Low |
| Quetiapine | Medium | Medium | High |
| Aripiprazole | Low | Low | Low |
| Ziprasidone | Low | Low | Low |
| Source: Reference 6 | |||
Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).
Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).
CASE CONTINUED: 10 LBS IN 10 WEEKS
At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).
Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.
Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.
- National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
- Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
- National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
- Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.
Drug brand names
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sibutramine • Meridia
- Ziprasidone • Geodon
Disclosure
Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.
At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?
This article answers those questions by addressing:
- clinical guidelines for diagnosing metabolic syndrome
- suggested intervals for monitoring at-risk patients
- strategies for managing metabolic abnormalities with lifestyle changes or medication.
CASE REPORT: 'FAT' AND FRUSTRATED
Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.
Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.
Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.
The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).
The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.
Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?
IMPLICATIONS OF METABOLIC SYNDROME
Patients with metabolic syndrome are at increased risk for:
In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.
DEFINING METABOLIC SYNDROME
Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.
According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:
- abdominal obesity
- insulin resistance
- high blood pressure
- elevated triglycerides
- below-normal HDL.
This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.
Table 1
5 defined risk factors* for metabolic syndrome
| Risk factor | Clinically significant level |
|---|---|
| Abdominal obesity | |
| Men | Waist circumference >40 in (102 cm) |
| Women | Waist circumference >35 in (88 cm) |
| Blood pressure | |
| Systolic | >130 mm Hg |
| Diastolic | >85 mm Hg |
| HDL count | |
| Men | <40 mg/dL (<1.04 mmol/L) |
| Women | <50 mg/dL (<1.30 mmol/L) |
| Fasting glucose | |
| Men, women | >110 mg/dL (>6.11 mmol/L) |
| Triglycerides | |
| Men, women | >150 mg/dL (>1.70 mmol/L) |
| * If 3 risk factors are present, suspect metabolic syndrome | |
| HDL: high-density lipoprotein cholesterol | |
| Source: Adapted from reference 5. | |
MONITORING FREQUENCY
Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6
Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).
Table 2
Suggested monitoring intervals for patients taking atypical antipsychotics*
| Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually | Every 5 years | |
|---|---|---|---|---|---|---|---|
| Personal/family history | X | X | |||||
| Weight (BMI) | X | X | X | X | X | ||
| Waist circumference | X | X | |||||
| Blood pressure | X | X | X | ||||
| Fasting plasma glucose | X | X | X | ||||
| Fasting lipid profile | X | X | X | ||||
| *Clinical status may warrant more-frequent assessments | |||||||
| BMI: Body mass index | |||||||
| Source: Reference 6. | |||||||
MANAGING METABOLIC PROBLEMS
Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:
- weight management, weight control education, and promoting regular exercise and a healthy diet
- switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
- working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.
Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.
Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7
Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.
Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19
In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.
Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:
- 43% had lower triglycerides than at baseline
- 16% had higher HDL cholesterol
- 38% had lower blood pressure
- 9% had improved fasting glucose
- 28% reduced their waist circumference.
Table 3
Interventions for specific metabolic complications
| Metabolic complication | Nondrug interventions8 | Medications |
|---|---|---|
| Abdominal obesity | Encourage weight loss | Sibutramine*† |
| Increase physical activity | Appetite suppressant | |
| Orlistat*† | ||
| Lipase inhibitor | ||
| Hypertriglyceridemia | Encourage weight loss | Fibrates9* |
| Increase physical activity | Reduce fasting and postprandial triglycerides 20% to 50% | |
| Increase low-glycemic-index food intake | Shift small dense LDL to large buoyant particles | |
| Reduce total carbohydrate intake | Increase HDL particles 10% to 35% | |
| Increase consumption of omega-3 fatty acids | Nicotinic acid10 | |
| Limit alcohol consumption | Reduces triglycerides 20% to 50% | |
| Statins11 | ||
| Reduce fasting and postprandial triglycerides 7% to 30% | ||
| Reduce LDL particles | ||
| Increase HDL particles | ||
| Reduce major coronary vascular events | ||
| Low HDL | Encourage weight loss | Nicotinic acid* |
| Increase physical activity | Increases HDL particles 15% to 35% | |
| Stop smoking | Fibrates9 | |
| Increase monounsaturated fat intake | See above | |
| Statins11 | ||
| See above | ||
| Hypertension | Encourage weight loss | ACE inhibitors* |
| Increase physical activity | May slow progression to diabetes12 | |
| Reduce saturated fat intake | Decrease CVD events13 | |
| Reduce sodium intake | Delay progression of microalbuminuria13 | |
| Limit alcohol consumption | Angiotensin receptor blockers | |
| May improve dyslipidemia associated with metabolic syndrome14 | ||
| Delay progression of microalbuminuria13 | ||
| Hyperglycemia | Encourage weight loss | Metformin,* thiazolidinediones |
| Increase physical activity | Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15 | |
| Reduce total carbohydrates | ||
| * Suggested first-line therapy. | ||
| † For patients with BMI 30 kg/m2 | ||
| ACE: Angiotensin-converting enzyme | ||
| CVD: Cardiovascular disease | ||
| HDL: High-density lipoprotein cholesterol | ||
| LDL: Low-density lipoprotein cholesterol | ||
Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.
By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21
In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22
Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).
Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.
Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6
Table 4
Atypical antipsychotics and their propensity for causing metabolic abnormalities
| Drug | Weight gain | Hyperglycemia | Dyslipidemia |
|---|---|---|---|
| Clozapine | High | High | High |
| Olanzapine | High | High | High |
| Risperidone | Medium | Medium | Low |
| Quetiapine | Medium | Medium | High |
| Aripiprazole | Low | Low | Low |
| Ziprasidone | Low | Low | Low |
| Source: Reference 6 | |||
Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).
Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).
CASE CONTINUED: 10 LBS IN 10 WEEKS
At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).
Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.
Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.
- National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
- Centers for Disease Control and Prevention: Body mass index formula for adults. http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
- National Heart, Lung and Blood Institute body mass index calculator. http://www.nhlbisupport.com/bmi/bmicalc.htm.
- Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.
Drug brand names
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sibutramine • Meridia
- Ziprasidone • Geodon
Disclosure
Dr. Bermudes is a speaker for Bristol-Myers Squibb Co. and Pfizer Inc.
1. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715-22.
2. Isomma B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.
3. Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998;148:958-66.
4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
5. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
6. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.
7. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998;6(suppl 2):51S-209S.
8. Darwin D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875-82.
9. Maki KC. Fibrates for treatment of the metabolic syndrome. Curr Atheroscler Rep 2004;6:45-51.
10. Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-85.
11. Showers JR. Effects of statins on the vasculature: implications for aggressive lipid management in the cardiovascular metabolic syndrome. Am J Cardiol 2003;91(suppl):14B-22B.
12. Yusuf S, Gerstein H, Hoogwerf B, et al. for the HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001;286:1882-5.
13. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.
14. Derosa G, Cicero AF, Bertone G, et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized double-blind study. Clin Ther 2004;26:1228-36.
15. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
16. Buchanan T, Xiang A, Peters R, et al. Prevention of type 2 diabetes by treatment of insulin resistance: comparison of early vs. late in the TRIPOD study [abstract]. Diabetes 2002;51(suppl 2):A35.-
17. Leon AS, Sanchez O. Meta-analysis of the effects of aerobic exercise training on blood lipids. Circulation 2001;104(suppl II):414-15 (abstract).
18. Fagard RH. Exercise characteristics and blood pressure response to dynamic physical training. Med Sci Sports Exerc 2001;33(6 suppl):S484-S492.
19. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33(6 suppl):S438-S445.
20. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 2003;35:1703-9.
21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.
22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.
23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.
24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.
25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.
1. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715-22.
2. Isomma B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.
3. Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998;148:958-66.
4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
5. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
6. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.
7. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998;6(suppl 2):51S-209S.
8. Darwin D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875-82.
9. Maki KC. Fibrates for treatment of the metabolic syndrome. Curr Atheroscler Rep 2004;6:45-51.
10. Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-85.
11. Showers JR. Effects of statins on the vasculature: implications for aggressive lipid management in the cardiovascular metabolic syndrome. Am J Cardiol 2003;91(suppl):14B-22B.
12. Yusuf S, Gerstein H, Hoogwerf B, et al. for the HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001;286:1882-5.
13. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.
14. Derosa G, Cicero AF, Bertone G, et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized double-blind study. Clin Ther 2004;26:1228-36.
15. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
16. Buchanan T, Xiang A, Peters R, et al. Prevention of type 2 diabetes by treatment of insulin resistance: comparison of early vs. late in the TRIPOD study [abstract]. Diabetes 2002;51(suppl 2):A35.-
17. Leon AS, Sanchez O. Meta-analysis of the effects of aerobic exercise training on blood lipids. Circulation 2001;104(suppl II):414-15 (abstract).
18. Fagard RH. Exercise characteristics and blood pressure response to dynamic physical training. Med Sci Sports Exerc 2001;33(6 suppl):S484-S492.
19. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33(6 suppl):S438-S445.
20. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 2003;35:1703-9.
21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.
22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.
23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.
24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.
25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.