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Educational Objectives


After reading this article, you will be familiar with:

• What constitutes metabolic syndrome.
• Why patients with schizophrenia are at increased risk for metabolic syndrome.
• How to manage metabolic syndrome in patients with schizophrenia.

Who will benefit from reading this article?

Psychiatrists, primary care physicians, neurologists, nurse practitioners, and other health care professionals. Continuing medical education credit is available for most specialists. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing board.

Dr Narasimhan is professor of psychiatry and director of biological research, Office of Biological Research in the department of neuropsychiatry and behavioral science at the University of South Carolina School of Medicine in Columbia. She reports that she has received a grant and/or research support from AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, and Janssen; she is on the speaker's bureau of Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen; and she is on the advisory boards of Bristol-Myers Squibb and Eli Lilly.

Ms Bailey is a third-year medical student at the University of South Carolina School of Medicine. She reports no conflicts of interest concerning the subject matter of this article.

Schizophrenia, a devastating mental illness that affects nearly 2.2 million Americans, is associated with high rates of morbidity and mortality.1 Individuals with schizophrenia have a 20% shorter life expectancy than the general population.1,2 Furthermore, among persons with schizophrenia, there is an increased prevalence of metabolic syndrome characterized by a constellation of risk factors, including insulin resistance, abdominal obesity, dyslipidemia, hyperglycemia, and hypertension,3 all of which contribute to the risk of cardiovascular morbidity and mortality.4 In fact, more than two thirds of patients with schizophrenia, compared with approximately half of the general population, die of coronary heart disease.2

In addition, metabolic syndrome is a global issue. Bobes and colleagues5 showed that the prevalence of coronary heart disease and metabolic syndrome in Spanish patients with schizophrenia who were treated with antipsychotics was the same as that in persons from the general population who were 10 to 15 years older.5 It has been suggested that patients with schizophrenia may have an inherent predisposition toward metabolic syndrome that is further complicated by their sedentary lifestyle, poor dietary habits, lack of access to care, poor insight, and medication-induced adverse effects.6

A number of studies have addressed some of the issues pertaining to the impact of metabolic abnormalities on overall quality of life. Weight gain and obesityincrease the risk of impaired physical health and may lead to nonadherence and decrements in subjective well-being.7-9 These studies have highlighted the deleterious effects of weight gain and its consequences on the long-term prognosis and life expectancy of patients with schizophrenia, and they emphasize the need to evaluate methods to prevent and treat weight gain in this population.

In recent years, mental health providers have been grappling with issues pertaining to metabolic disturbance in schizophrenia as well as the adverse effects of antipsychotic treatments. Recent trials estimate that rates of obesity and diabetes in those with schizophrenia are nearly twice that in the general population, and dyslipidemias are more common.10 The prevalence of smoking is 3 times that seen in the general population. These risks translate into cardiovascular morbidity and mortality with a risk twice that of the general population.10 A growing body of clinical and translational research evidence has implicated atypical antipsychotics in causing and worsening weight gain, dyslipidemia, and diabetes,11 resulting in "an epidemic within an epidemic."12

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, one of the largest studies of schizophrenia to date, compared metabolic syndrome in its sample with an age-matched sample from the general population drawn from the National Health and Nutrition Examination Survey (NHANES).13 The prevalence of metabolic syndrome at baseline was higher in the CATIE participants than in the NHANES participants. In the CATIE study, the overall prevalence of hypertension was 33.2%. The prevalence of diabetes was 10.4% for the entire cohort, with a prevalence of 10.9% in patients with fasting glucose results obtained 8 hours or more after their last meal. Dyslipidemia, as defined by elevated serum triglyceride levels, was found in 47.3% of fasting patients and when defined as low serum levels of high-density lipoprotein (HDL) cholesterol, it was found in 48.3% of all patients. Rates of nontreatment ranged from 30.2% for diabetes to 62.4% for hypertension and 88.0% for dyslip- idemia.14 These data reiterate the dilemma confronting practitioners in clinical practice on how best to determine strategies that would change the long-term adverse health consequences of these conditions.

Metabolic syndrome: do we have a universal consensus?

While metabolic syndrome is a growing concern for patients with mental illness, there is no universal agreement on precisely what metabolic syndrome is or how to concisely define it, thus making the diagnosis of metabolic syndrome an ambiguous task. Controversies stem from guidelines with different diagnostic criteria and debate over whether the syndrome represents anything more than the risk associated with these individual abnormalities.15

Metabolic syndrome is defined as a cluster of clinical and laboratory test result abnormalities including abdominal obesity, insulin resistance, hypertension, low levels of HDL cholesterol, and high levels of triglycerides—all of which can pose significant risk for cardiovascular morbidity and mortality.4 The most recent definitions come from the International Classification of Diseases-9th revision, the International Diabetes Federation (IDF), the World Health Organization (WHO), the American Heart Association, the American Diabetes Association, the NIH, and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). The most commonly applied definitions are from the WHO, the NCEP ATP III, and the IDF, and each includes slightly varying criteria (Table 1).16-18

Risk factors such as abdominal obesity, fasting triglyceride levels, HDL cholesterol levels, blood pressure, and fasting glucose levels are included in the criteria when diagnosing metabolic syndrome.16-18 Other important and potentially modifiable risk factors may also warrant consideration, including elevated levels of low-density lipoprotein (LDL) cholesterol, family history of premature coronary heart disease (age 45 years or youn- ger for men and 55 years or younger for women), ethnicity, postmenopausal status, cigarette smoking, diet, alcohol consumption, and exercise or lack of activity either with or without weight changes.13

While the current definitions seem to imply that the different components of metabolic syndrome are equal in importance, analyses of the components of metabolic syndrome have shown that the individual components are not necessarily equally associated with the risk for coronary heart disease.13 In fact, most of the risk associated with metabolic syndrome is linked with age, blood pressure, diabetes, and HDL cholesterol.13 Therefore, the burden of diagnosis is placed on the physician, who must closely monitor patients who are taking antipsychotics, especially atypical antipsychotics.

Antipsychotic drugs and metabolic syndrome: pathophysiology

Typical antipsychotics, especially low-potency phenothiazines, have been associated with significant weight gain, diabetes, and increased plasma lipid levels.19 Dramatic weight gain, diabetes, fatal ketoacidosis, and dyslipidemias following antipsychotic use have raised concerns and demand further scrutiny.19,20 In the vast majority of cases, weight gain and central adiposity are major players in the pathophysiology of antipsychotic-induced metabolic syndrome. Increasing visceral/ abdominal adiposity (assessed by measuring waist circumference or body mass index [BMI]) is directly linked to insulin resistance, risk of diabetes, and dyslipidemias.

The mechanism of weight gain with antipsychotic drugs is a multifactoral phenomenon that includes appetite-stimulating effects, genetic factors, sedentary lifestyle, and impaired metabolic regulation. The pathophysiology of weight gain is mediated through monoaminergic, cholinergic, and histaminergic neurotransmission.21 Differential affinities for the serotonin 5-HT2C and H1 receptors22,23 may explain the greater weight gain seen with clozapine and olanzapine.22,24 Despite its potent 5-HT2c antagonism, ziprasidone is associated with the least amount of weight gain, which may be attributed to its low H1 antagonism.25 Aripiprazole is a close second to ziprasidone in associated weight gain.

Antipsychotic-induced weight gain can increase the risk of various comorbidities, including cardiovascular morbidity that can adversely impact the patient's quality of life.26 Obesity is a risk factor for insulin resistance, hyperglycemia, and type 2 diabetes.27 Metabolic disturbances associated with atypical antipsychotics may be a direct consequence of the alteration of insulin sensitivity and/or insulin secretion. Antipsychotic-induced weight gain and metabolic liability,28 along with impaired parasympathetic regulation of b cell activity mediated by the blockade of histaminergic and muscarinic receptors, may contribute to increased metabolic risk.29 Antipsychotic agents may directly impair glucose transporter function by alterations in the insulin signaling pathway, resulting in elevated circulating glucose levels, compensatory insulin hypersecretion, and reduced insulin sensitivity, and thus lead to type 2 diabetes and metabolic syndrome.30

Antipsychotics, both typical and atypical, affect serum lipid levels to varying degrees. Clozapine and olanzapine can cause greater increases in triglyceride levels than typical antipsychotics and other atypical antipsychotics.31 Several factors play a role in dyslipidemias, including diet, weight gain, mental illness, and antipsychotics. Elevated fasting plasma triglyceride levels are an important indicator of potential insulin resistance and possible increases in fasting insulin levels.32 This serves as a valuable marker for evaluating a patient's potential risk for metabolic syndrome and cardiovascular disease. A direct correlation between increased adiposity and increased LDL cholesterol and decreased HDL cholesterol levels has been demonstrated.33 The NCEP ATP III has identified LDL cholesterol as the primary target for reducing risk of cardiovascular disease.16

Antipsychotic-induced weight gain and dysregulation of other metabolic parameters may predispose patients with mental illness to cardiovascular morbidity and mortality.26 The risk of coronary artery disease is increased in the presence of metabolic syndrome characterized by 3 of the following: insulin resistance (with or without glucose intolerance); atherogenic dyslipidemia (elevated triglyceride levels, low HDL cholesterol levels, and small dense LDL particles); hypertension; abdominal obesity; and prothrombotic and proinflammatory states.16 The metabolic risks associated with various atypical antipsychotics are outlined in the American Diabetes Association-American Psychiatric Association (ADA-APA) Consensus Guidelines Panel (Table 2).34

The prevalence of metabolic syndrome in the CATIE study was 42.7% at baseline, approximately twice that found in the general population14 with lower rates of treatment for the metabolic disturbance. In this study, olanzapine and clozapine demonstrated the highest risk for metabolic dysfunction. Ziprasidone appeared metabolically neutral. It is not surprising that atypical antipsychotics are associated with an elevated risk of metabolic syndrome, given the body of evidence linking them to weight gain, hyperglycemia, and lipid abnormalities.20 On the other hand, several studies have failed to detect differences in the prevalence of the syndrome between patients taking atypical antipsychotics and those taking typical antipsychotics, raising an important question of whether metabolic syndrome is underresearched and underestimated with typical antipsychotics.16-27

Screening and monitoring during the use of atypical antipsychotics

It is prudent to evaluate a patient for metabolic and cardiovascular risk before initiating antipsychotic treatment and to closely monitor these factors throughout treatment. A number of authoritative guidelines have been recommended, including the Mount Sinai Conference on medical monitoring and more recently, the ADA-APA Consensus Guidelines developed with the American Association of Clinical Endocrinologists and the North American Association for the Study of Obesity.34 These guidelines are a by-product of extensive review of the clinical literature examining metabolic changes associated with the use of atypical antipsychotics, and they provide us with a wide range of monitoring and management guidelines for assessing physical health needs and reducing morbidity and mortality in the mentally ill.

Cohn and Sernyak35 reviewed the 6 major consensus guidelines published in 2004 and 2005 for metabolic monitoring of patients treated with antipsychotics, including the guidelines published by the Mount Sinai Conference, the ADA-APA, and experts in Australia, Belgium, the United Kingdom, and Canada. They determined that areas of dissent include the frequency of monitoring various signs and symptoms, which patients to monitor, the utility of glucose tolerance testing, and the point at which to consider switching antipsychotics. The authors concluded that there is considerable consensus among the published guidelines, including a systematic assessment of:

• Family history.
• Weight and BMI.
• Waist circumference.
• Blood pressure.
• Fasting lipid levels.
• Fasting glucose levels.

According to the ADA-APA Consensus Guidelines, weight should be reassessed at weeks 4, 8, and 12 after initiating or changing an antipsychotic agent, and quarterly thereafter.34 A weight gain of 5% or more of initial body weight warrants lifestyle modification with diet and exercise and/or therapeutic alternatives, including drug switch strategies. Fasting plasma glucose levels, lipid profile, and blood pressure should be assessed every 3 months on initiation of antipsychotic therapy and sooner in persons who are at high risk at baseline.34 Compared with a fasting glucose test, a postload oral glucose tolerance test is an earlier indicator of failing glucose control.

TABLE 3
Barriers to integrated care in the mentally ill38
System-related issues
Limited resource in public mental health systems, which serve a greater proportion of clients with schizophrenia
Reimbursement issues
 
Provider-related issues
Resistance to change among providers
Lack of familiarity with monitoring guidelines
Other competing demands in mental health systems
 
Patient-related issues
Psychopathology-related barriers, including paranoia and mania
Cognitive deficits
Access and affordability to medical care
Nonadherence to treatment recommendations


Implementation of such guidelines can substantially improve the health of patients with schizophrenia but can be quite challenging to adopt in clinical practice. The Atypical Antipsychotic Therapy and Metabolic Issues National Survey in 2004,36 and more recently a nationwide database study by Cuffel and colleagues37 showed low rates of monitoring for metabolic risks. Our field needs to acknowledge patient-related, physician-related, and system-related barriers to implementing these guidelines (Table 3).38 These barriers highlight an urgent need to transform public mental health through early intervention, integrated medical and psychiatric care, and customizing treatments to enhance subjective wellness and recovery (Table 4).38

TABLE 4
Strategies to overcome barriers to foster monitoring and collaborative management38
• Educating clinicians on metabolic and cardiovascular risks in patients with mental illness as well as the implications of treatment with atypical antipsychotics
• Impressing upon clinicians evidence-based standards highlighting the value of monitoring patients and implementing appropriate intervention
• Establishing therapeutic alliance with patients that would enhance communication and foster adherence to monitoring guidelines and management
• Working toward an integrated collaborative model in the public, private, and federal sector to decrease metabolic and cardiovascular morbidity and mortality in the mentally ill
• Implementing some simple steps, including lifestyle modification (diet and exercise), smoking cessation, and substance abuse relapse prevention as part of routine case management
• Pursuing switch strategies to diminish the catastrophic effects on metabolic risk without unduly compromising efficacy, based on patient profiles and clinicians' judgment


Integration of psychiatric and general medical treatment

Treatment with atypical antipsychotics imposes new standards for patient education, informed consent, and risk-benefit analysis in the selection of pharmacotherapy. The NCEP ATP III treatment guidelines recommend lifestyle modification, including reduced intake of saturated fats and cholesterol, increased fiber intake, weight reduction, and increased physical activity, as the first-line therapeutic approach to reduce the risk of cardiovascular disease.16 Monitoring guidelines suggest consideration of switching to an atypical antipsychotic with less weight gain liability if a patient gains more than 5% of his or her baseline weight or dyslipidemia or hyperglycemia worsens. Behavioral approaches that use educational, motivational, and pragmatic techniques to achieve weight loss in patients with schizophrenia have had variable success. Guidelines for weight reduction are outlined in Table 5.39

TABLE 5
Weight reduction guidelines39
• The initial goal of weight loss therapy should be to reduce body weight by approximately 10% from baseline
• Weight loss targets should be about 1 to 2 lb/wk for 6 months
• Weight loss and weight maintenance therapy includes low-calorie diets, increased physical activity, and behavior therapy
• Weight loss drugs should never be used without concomitant lifestyle modifications and continued risk-benefit analysis
• After successful weight loss, a maintenance program consisting of dietary therapy, physical activity, and behavior therapy should be continued


The NCEP ATP III guidelines suggest that weight loss lowers LDL cholesterol and triglyceride levels, increases HDL cholesterol levels, lowers blood pressure, and reduces insulin resistance.16 When clinically indicated, LDL-lowering drugs, including HMG-CoA reductase inhibitors (statins), nicotinic acid, bile acid sequestrants, and fibric acids are necessary to achieve target LDL cholesterol levels. Statin therapy has been shown to significantly decrease triglyceride, total cholesterol, LDL cholesterol, and non-HDL cholesterol levels without changing HDL cholesterol levels, BMI, waist circumference, or glucose homeostasis.40

Metformin and the thiazolidinedione class of drugs reduceinsulin resistance and new-onset coronary heart disease in obese patients with diabetes and prevent or delay type2 diabetes in patients with impaired glucose tolerance.27 Hypertensive patients who are taking atypical antipsychotics and meet criteriafor metabolic syndrome should be treated with therapeuticlifestyle changes and medications in accordance with hypertensionguidelines.27 Finally, low-dose aspirin may be helpful in reducing the prothrombotic state in patients with metabolicsyndrome and an elevated risk of coronary heart disease.27

Switch strategies

Studies have suggested that switching to a medication with a lower weight-gain liability may produce significant reductions in body weight if therapeutic lifestyle modification strategies fail. The ADA-APA Consensus Guidelines suggest that clozapine and olanzapine have the greatest propensity for weight gain, risperidone and quetiapine have an intermediate risk, and ziprasidone and aripiprazole have minimal effects on weight (Table 2).41

Studies have shown that patients had an average weight increase of 6.8 to 11.8 kg with olanzapine, 5.3 to 6.3 kg with clozapine, 2.8 to 5.6 kg with quetiapine, and 2.0 to 2.3 kg with risperidone after the first year of therapy, and after 6 months of therapy, patients had an increase of 0.23 kg with ziprasidone on average.42-53 Other studies have shown that patients treated for 1 year gained an average of 2.6 kg with aripiprazole, 6.26 kg with olanzapine, and 2.3 kg with risperidone.49,54,55 The CATIE study found that patients being treated with olanzapine gained an average of 2 lb per month, while patients being treated with risperidone and quetiapine gained an average of 0.4 and 0.5 lb per month, respectively. Patients who were being treated with ziprasidone lost an average of 0.3 lb per month; however, most of the patients were taking another antipsychotic before switching to ziprasidone, which may account for the result.56

Weiden and colleagues57 showed that patients switching from olanzapine or risperidone to ziprasidone lost an average of 1.8 kg and 0.9 kg, respectively, over 6 weeks. In addition, Casey and colleagues58 showed that patients switching from olanzapine or risperidone to aripiprazole lost an average of 2 kg and 0.7 kg, respectively. Simpson and colleagues59 showed that patients who continued to take ziprasidone after switching from olanzapine lost an average of 10 kg over 58 weeks, while patients who took ziprasidone after switching from risperidone lost an average of 6.8 kg over 58 weeks.59 Weight loss has occurred with a switch to ziprasidone or aripiprazole from medications that have a greater propensity to induce weight gain; otherwise, when switching from agents with similar weight profiles, there are no weight-loss benefits. Therefore, a switch to ziprasidone or aripiprazole is effective to reverse weight gain induced by other atypical antipsychotics, such as olanzapine or risperidone.

Weight loss and reversal of metabolic effects with switch strategies far exceeds that with use of adjunctive medications. However, if weight gain occurs despite these measures, several weight loss agents, including metformin,60,61 amantadine,62 topiramate,63 nizatidine,64 sibutramine, and orlistat,23 have been suggested. Current evidence does not support the general use of pharmacological interventions for patients with antipsychotic-related weight gain, although some patients may benefit from it.65

Medications associated with significant increases in total cholesterol levels and triglyceride levels include clozapine, olanzapine, quetiapine, and risperidone, whereas aripiprazole and ziprasidone cause decreases in total cholesterol levels. The CATIE study showed that olanzapine and quetiapine are associated with increases in total cholesterol levels of 9.4 mg/dL and 6.6 mg/dL, respectively; and increases in triglyceride levels of 40.5 mg/dL and 21.2 mg/dL, respectively.56 Risperidone and ziprasidone are associated with decreases in cholesterol levels of 1.3 mg/dL and 8.2 mg/dL and decreases in triglyceride levels of 2.4 mg/dL and 16.5 mg/dL, respectively.56

A literature review by Newcomer20 reported that clozapine and olanzapine cause sustained elevations in lipid levels, but there is limited if any increased risk from treatment-induced dyslipidemia with risperidone or quetiapine. Newcomer also reported a lack of evidence indicating that aripiprazole and ziprasidone cause dyslipidemia. In a 58-week study, Weiden and colleagues66 showed that switching from olanzapine to ziprasidone resulted in an average decrease of 20 mg/dL in cholesterol levels and an average decrease of 17 mg/dL in triglyceride levels, and switching from risperidone to ziprasidone resulted in an average decrease of 13 mg/dL in cholesterol levels. In a study by Litman and colleagues,67 switching from olanzapine to aripiprazole decreased total cholesterol levels by an average of 39.1 mg/dL and decreased LDL cholesterol levels by an average of 28.9 mg/dL over 12 weeks.

In addition to weight gain and lipid abnormalities, patients who received clozapine and olanzapine were shown to have significant elevations in glucose levels and reductions in insulin sensitivity compared with healthy controls. Aripiprazole and ziprasidone, on the other hand, are associated with an overall improvement of metabolic components.

In a retrospective study using a cutoff of 126 mg/dL for fasting blood glucose levels, clinically significant elevations were seen in 44% of patients treated with clozapine, 27% treated with olanzapine, 36% treated with risperidone, and 13% treated with quetiapine.68 When using a cutoff of 200 mg/dL for random blood glucose levels, clinically significant elevations were seen in 4% of patients treated with clozapine, 5% treated with olanzapine, 8% treated with risperidone, and 0% of patients treated with quetiapine. In addition, clinically significant elevations in total cholesterol levels (200 mg/dL) were seen in 48% of patients receiving clozapine, 25% of those receiving olanzapine, 21% of those receiving risperidone, and 25% of patients receiving quetiapine.68

How to switch

A clinician should choose to switch to a new antipsychotic based on the reason behind the decision to change medications and on the metabolic adverse-effect profiles of each drug (current and new) as determined by the literature. A clinician must also consider the differential efficacies of the antipsychotics, particularly if a patient has a good therapeutic response to the current medication. Another consideration is the potential to maintain long-term efficacy and the potential for the development of tolerance to a new medication. Therefore, the clinician must determine whether a switch in antipsychotics for metabolic concerns is realistic for the patient's overall treatment goals.

Before switching antipsychotics, patients need to be informed of the potential risk of relapse. A gradual cross-taper over several weeks is suggested.41,69,70 Medication changes and adjustments need to be tailored to patients based on their risk- to-benefit ratio, with some consideration given to antipsychotics with fairly neutral metabolic side-effect profiles.

Data from the CATIE study using number needed to treat (NNT) and number needed to harm (NNH) in assessing efficacy tolerability, and risk of weight gain in antipsychotics showed an advantage for olanzapine for all-cause discontinuation, with a NNT of 6 for olanzapine versus quetiapine, 11 for olanzapine versus risperidone, and 7 for olanzapine versus ziprasidone.71 While an efficacy advantage was shown for olanzapine in every 8 to 11 patients, a tolerability disadvantage was determined for every 12 to 31 patients. While NNT and NNH are predictors of events, either adverse or desired, there are no guarantees of weight changes, drug efficacy, or changes in other metabolic parameters, thus indicating that the decision to switch or to continue taking a particular antipsychotic must be highly individualized.71

Correll72 indicated 8 distinct switch strategies in a recent article and discussed situations in which the various strategies could be best used when changing from one antipsychotic to another.73 An individualized approach to switching antipsychotics was acknowledged as reasonable when considering the adverse effects leading to the medication switch and the adverse effects that may occur secondary to the medication change.72 Correll noted that when switching to the metabolically neutral antipsychotics ziprasidone and aripiprazole, an overlapping switch strategy may be more effective to avoid withdrawal and/or rebound from the antihistaminic and anticholinergic blockades, which may cause "activating" adverse effects.72 However, further research is needed to develop treatment guidelines for safely and effectively switching antipsychotics.

The following case vignette illustrates some of the challenges and complexities involved in addressing weight gain and metabolic syndrome in a patient receiving antipsychotic therapy.

Case Vignette

Mr J is a 36-year-old white man with a history of chronic schizophrenia, paranoid type. His first psychotic break occurred during his junior year of college at the age of 21, and he required hospitalization. Before this, he had been a successful student and athlete with many close friends. During the hospitalization, treatment was started with fluphenazine. Shortly thereafter, he attempted to return to college, but was unable to continue classes because of intermittent exacerbations of psychosis. Subsequent worsening of symptoms resulted in numerous lengthier hospitalizations over the next 5 years.

He was treated with a variety of medications before being stabilized on risperidone for almost 6 years. During these years, Mr J was able to maintain a job, remained living at home with his parents, and pursued a few extracurricular activities. He gained approximately 30 lb while taking the medication and his BMI increased from 25.8 to 30.1. Because of the progression of weight gain, an attempt was made to switch him to antipsychotics such as ziprasidone and aripiprazole; this resulted in a positive outcome on the weight parameter, but unfortunately, the psychotic symptoms re-emerged. He resumed treatment with risperidone.

He presented to the clinic weighing 215 lb at 5 ft 10 in (BMI, 30.8) with a waist circumference of 42 in and a blood pressure of 140/88 mm Hg. His total cholesterol level was 205 mg/dL; triglyceride level, 232 mg/dL; LDL cholesterol level, 152 mg/dL; HDL cholesterol level, 30 mg/dL; and fasting plasma glucose level, 110 mg/dL. Results of other laboratory tests including complete blood cell count, complete metabolic profile, thyroid function tests, and urinalysis were unremarkable. Mr J denied any substance use. His family history is significant for maternal and paternal hypertension and hyperlipidemia, schizophrenia in his mother, and the death of his father at age 60 due to a myocardial infarction.

By definition, Mr J met 4 of the 5 NCEP ATP III criteria—including waistcircumference, total triglyceride level, HDL cholesterol level, and bloodpressure—for a diagnosis of metabolic syndrome. Elevated triglyceride levels, low HDL cholesterol levels, hypertension, and family history of premature death from coronary heart disease put him at an increased risk for coronary heart disease. Although there is no evidence of coronary heart disease at this time, the NCEP ATP III guidelines initially recommend therapeutic lifestyle changes, including a reduction in the intake of saturated fat and cholesterol, an increase in physical activity, and weight loss with weight control. Mr J was referred to an internist because of the metabolic problems and began a treatment plan coordinated between his psychiatrist and internist to monitor the parameters of his metabolic syndrome every 3 months.

Mr J attempted these lifestyle changes over 12 weeks with little change in his lipid levels but a 10-lb weight loss after 12 weeks. At this point, his internist added a statin to lower his lipid levels to the target range. In addition to these efforts, Mr J and his psychiatrist implemented strategies that encouraged Mr J to expand his social connections and improve his health. He began attending a weekly support group and started working out with a personal trainer. Mr J has been able to hold a job and find increasing meaning in his life, which further encourages and motivates him to continue with his treatment plan for a healthier lifestyle and a better social life.

Discussion

The debate on whether metabolic effects induced by atypical antipsychotics are a class effect or a differential effect continues to spark a great deal of interest, although the phenomenon is poorly understood. Despite evidence suggesting that the risk of diabetes and metabolic syndrome forthe various atypical antipsychotics is strongly correlated with weight gain,20,34 there is a paucity of evidence as to whether atypical antipsychotics that are weight neutral or have minimal effects on weight gain have a propensity to cause diabetes and metabolic syndrome. Patients with chronic mental illness generally represent a high-risk group,and the ADA-APA Consensus Guideline Panel recommendsmetabolic monitoring and clinical vigilance for all patients who are taking atypicalantipsychotics.34

Before initiating treatment with an antipsychotic, identifying high-risk individuals who are likely to gain weight is considered prudent practice. Complications of weight gain and other metabolic abnormalities in patients taking antipsychotics may be prevented by choosing an agent that is effective and that is associated with a lower incidence of weight gain. Health care providers should start by educating their patients about the risks and benefits associated with psychotropics, allowing for a shared decision, which is the first step toward treatment adherence. Counseling patients on proper diet and exercise needs to be an integral part of the treatment plan. Participation in treatment programs that emphasize a healthy diet, exercise, and lifestyle modification to lose weight needs to be strongly recommended to overweight and obese patients.

Psychiatry lacks clear-cut, definitive guidelines to aid clinicians in switching antipsychotics. When switching from one antipsychotic to another is clinically warranted because of intolerable adverse effects, the clinician should be aware of a number of potential risks associated with this strategy. Awareness of these risks and open communication with the patient concerning them can help the clinician manage problems that may occur during the switch process.

Many patients with schizophrenia receive little or no medical care. Often individuals with serious mental illness have had inadequate evaluation and treatment of medical illnesses. Several provocative questions continue to remain unanswered.

• How does the increasing prevalence of metabolic syndrome shape the way we practice medicine?
• What does this mean for a mental health provider?
• How do we begin to move toward creating collaborative models that would address some of these issues that clearly have implications for the overall life expectancy of our clients?

The field of psychiatry has seen a flurry of guidelines that have raised awareness of the magnitude of this problem and the need to stringently monitor this vulnerable patient population. But, given the issues pertaining to adherence, affordability of care, resources, and financial constraints which our society faces, translating these management guidelines into clinical practice has been quite challenging. Although this is discouraging, it also presents the unique public health opportunity for health care providers to strive to increase awareness of the physical health of patients with mental illness. This, in turn, may help establish a comprehensivemodel of care that integrates medical and psychiatric management to improve the overall health of patients with schizophrenia.

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