Managing Metabolic Syndrome in Schizophrenia

Managing Metabolic Syndrome in Schizophrenia
Managing Metabolic Syndrome in Schizophrenia

Patients with schizophrenia carry a heightened risk for developing metabolic syndrome (MetS). The prevalence of dyslipidemia, hypertension, obesity, and type 2 diabetes is approximately 1.5 to 2 times higher in individuals with schizophrenia and related disorders than in the general population,1 with estimates of MetS prevalence in adults with schizophrenia ranging between 20–60%.2 People with schizophrenia and related disorders have a reduced life expectancy compared to the general population, with a nearly doubled risk of dying from cardiovascular disease.2

Although patients most vulnerable to MetS are those taking second generation antipsychotics (SGAs), several studies have found that even treatment-naive patients are at risk, showing impaired glucose tolerance, increased insulin resistance, and increased visceral fat distribution, compared with normal controls.3-5 It is possible that diabetes and schizophrenia share familial risk factors or a common genetic disposition.6 Additional risk factors include sedentary lifestyle, poor diet, substance use, high rates of smoking,7 and longer duration of illness.8

These disturbing statistics make it urgent to address MetS in the schizophrenia population. In her recent article "Interventions for the Metabolic Syndrome in Schizophrenia: A Review,"6 Papanastasiou summarizes the efficacy of currently available interventions for preventing and treating MetS and reviews consensus guidelines for monitoring patients taking SGAs.

The author reviews 95 original studies of which 42 investigated behavioral and 44 targeted pharmacologic interventions. Nine studies tested the efficacy of combined behavioral and pharmacologic interventions.

Behavioral Interventions

Behavioral interventions reviewed by Papanastasiou included holistic well-being programs, cognitive behavioral therapy (CBT), nutritional education, weight management, and psychoeducation. The author reports that well-being support programs (consisting of holistic approaches or exercises) showed some modest evidence of success in improving general physical health and cardiovascular fitness in people with schizophrenia and related disorders. Caloric restriction, combined with nutritional education and behavioral or motivational strategies, showed effectiveness in tackling weight gain. Most comprehensive weight reduction programs that included an array of components (diet, exercise, and general and lifestyle modification counseling) were helpful in improving weight, reducing smoking, and improving self-esteem.

Pharmacologic Interventions

Maayan performed a literature review of pharmacologic interventions designed to attenuate antipsychotic-related weight gain to rank interventions in order of efficacy in reducing weight (from the most efficacious to the least).9 Numerous pharmacologic interventions showed promise in improving risk factors for MetS. These included metformin, d-fenfluramine, sibutramine, topiramate, reboxetine, amantadine, nizatidine, orlistat, metformin plus sibutramine, famotidine, dextroamphetamine sulfate, fluoxetine, and rosiglitazone.9 The author adds that atomoxetine, chlorphenetermine, phenmetrazine, and phenylpropanolamine were not effective in reducing antipsychotic-induced weight gain. Findings from nizatidine and fluvoxamine studies were contradictory.

Studies of Combined Behavioral and Pharmacologic Interventions

Several studies attempted to test the efficacy of combining behavioral and pharmacologic interventions. The author noted that combination of NR and/or bupropion and behavioral techniques (group therapy, motivational enhancement, positive reinforcement, CBT, and anxiety reduction) helped maintain abstinence from smoking. Metformin and lifestyle intervention was found more effective than either intervention alone in addressing weight loss.

Monitoring Patients for MetS

The author points to the paramount importance of using a "rigorous monitoring plan" for early detection of incipient MetS. Several sets of consensus guidelines lay out monitoring protocols, which include an array of components (depending on the particular guideline): personal and family history; baseline electrocardiogram (ECG), obtaining urea, electrolytes, prolactin levels, and complete blood count at baseline and at specified intervals thereafter; and measurement of weight and waist circumference, fasting plasma glucose, fasting plasma lipids, and blood pressure both at baseline and at specific intervals thereafter.10-13


The author concluded that, although findings were inconsistent, almost all behavioral interventions appeared to have some benefit for patients, either toward improving physical health, lifestyle habits (ie, smoking, exercise, and diet), or health perception and views. Pharmacologic interventions antipsychotic-induced weight gain were supported by "more robust studies." But better outcomes were achieved through combining pharmacologic and nonpharmacologic interventions than using either alone.

The author noted that guideline implementation is still sorely lacking among clinicians, and emphasized the critical importance of "monitoring, monitoring, monitoring." Monitoring regimens can vary, depending on the particular guideline the clinician is using and the needs of the individual patient.


1.    Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19(suppl 1):1-93.

2.    Riordan HJ, Antonini P, Murphy MF. Atypical Antipsychotics and Metabolic Syndrome in Patients with Schizophrenia: Risk Factors, Monitoring, and Healthcare Implications. Am Health Drug Benefits. 2011;4(5):292-302.

3.    Thakore J, Mann J, Vlahos I, et al. Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia. Int J Obes Relat Metab Disord. 2002;26(1):137–141.

4.    Venkatasubramanian G, Chittiprol S, Neelakantachar N, et al. Insulin and insulin-like growth factor-1 abnormalities in anti psychotic-naive schizophrenia. Am J Psychiatry. 2007;164(10):1557–1560.

5.    Fernandez-Egea E, Miller B, Bernardo M., et al. Parental history of type 2 diabetes in patients with nonaffective psychosis. Schizophr Res. 2008;98(1):302–306.

6.    Papanastasiou E. Interventions for the metabolic syndrome in schizophrenia: a review. Ther Adv Endocrinol Metab. 2012;3(5):141-162.

7.    De Hert M, Dekker J, Wood D, et al. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur Psychiatry. 2009;24(6):412–424.

8.    Mitchell AJ, Vancampfort D, Sweers K, et al. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis. Schizophr Bull. 2011. December 29;[Epub ahead of print].

9.    Maayan L, Vakhrusheva J, Correll C. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology 2010;35(7):1520–1530.

10. Barnett A, Mackin P, Chaudhry I, et al. Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia. J Psychopharmacol. 2007;21(4): 357–373.

11. De Hert M, Schreurs V, Vancampfort D, Van Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry. 2009; 8(1):15–22. (B)

12. Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines. London; Informa Healthcare:2009.

13. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):599.

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