By Professor Ya Mei Bai, M.D, Ph.D. 

Metabolic syndrome (MetS) is a combination of risk factors, including weight gain, abdominal or visceral adiposity, dyslipidemia and elevated plasma glucose that increase the risk of developing cardiovascular disease and diabetes mellitus.

The increased risk of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder, major depressive disorder (MDD), and schizophrenia, has gained much attention, because the excess mortality of these patients is mainly due to physical illness. Compared to the general population, many studies showed that metabolic syndrome is 2–3 times more common in patients with these SMDs. Patients with bipolar disorder and schizophrenia had comparable prevalence of metabolic syndrome, ranging from 32%to50%. The possible causes of the increased comorbidities included a sedentary lifestyle, eating behavior, genetic factors, increased nicotine dependency, and psychotropic medications, including antipsychotics and mood stabilizers. Among the antipsychotics, clozapine and olanzapine were associated with the highest risk of weight gain; quetiapine and risperidone with an intermediate risk, ziprazidone and aripiprazole with the least risk of metabolic side effects. In general, the rank order of risk observed for these antipsychotic medications suggests that the differing weight gain liability of atypical agents contributes to the differing relative risk of metabolic side effects. For the mood stabilizers, approximately 30% of lithium- treated patients gained weight 4–10kg in 1year. The use of valproic acid increased fast food fats cravings, and induced similar weight gain (around 6kg in one year). Regarding the patients with depression, the research results are inconsistent. Although some evidences showed patients with depression have a twofold risk of obesity, 1.6–3 times increased risk of diabetes, and an increased risk of cardiovascular disease, a comprehensive meta-analysis showed that amitriptyline, mirtazapine, and paroxetine were associated with a greater risk of weight gain; in contrast, some weight loss occurred with fluoxetine and bupropion. In conclusion, the long-term effect of antidepressants on metabolic side effects may vary greatly depending on the individual’s characteristics.

Modifiable and non-modifiable risk factors can contribute to overall metabolic risk. It is important to assess modifiable risk factors in individual patients to evaluate patient risk of cardiovascular and metabolic diseases. The association between mental illness and increased metabolic risk, particularly the association between psychiatric medications and risk, suggests a role for psychiatrists and other mental healthcare clinicians in monitoring risk and in assessing risk in relation to prescribing antipsychotic medications. Modifiable risk factors that should be evaluated at or near baseline and serially after prescription of antipsychotics include: body weight, waist circumference, fasting plasma lipids (total, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol, and triglycerides), fasting and/or post load (or perhaps postprandial) plasma glucose, and blood pressure. Patients who smoke should be instructed to quit and should be provided with support, including counseling and smoking cessation aids. Laboratory parameters should be monitored periodically, paying particular attention to changes in any value after initiation of a new antipsychotic agent.

Weight gain associated with atypical antipsychotic agents generally occurs within the first few months after initiation and may not stabilize for more than a year. The American Diabetes Association (ADA) recommends weight monitoring at 4, 8, and 12 weeks after initiating a change in antipsychotic therapy, and quarterly thereafter. In addition to monitoring by physicians, patients should be encouraged to track their own weight and waist circumference. The introduction of regular routine monitoring should allow for the early detection of changes in these important risk factors, and so improve the overall long-term health of patients with schizophrenia and other mental illnesses.