Dangerous Liaisons: Schizophrenia and Diabetes

Pharmacy Times
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There should be a law that people with one chronic disease cannot succumb to a second. Unfortunately, lawlessness prevails, and some chronic illnesses appear in tandem. Such is the case with schizophrenia and diabetes. Their frequent juxtaposition on a patient's medical chart is all too common, creating patient and caregiver burden alike. Both conditions compound quality-of-life issues and often lead to other conditions, such as depression, requiring additional medication (Table 1).1

The life expectancy of schizophrenia sufferers is 20% shorter?and their risk of developing diabetes 2 to 4 times greater?than that of the general population.2,3 Approximately 18% of the schizophrenia population has type 2 diabetes.2 A "black box warning," added in 2003, describes the association of all atypical antipsychotics with hyperglycemia and diabetes. Schizophrenia patients taking these medications are at additional increased risk for metabolic syndrome (obesity, elevated fasting plasma glucose [FPG] levels, elevated triglyceride levels, low high-density lipoprotein cholesterol levels, and hypertension).

The risk for metabolic syndrome and diabetes for patients with schizophrenia appears to be intrinsically elevated. Studies of neuroleptic-naive, first-episode schizophrenia patients find that they have a greater number of clinical risk indicators than matched controls.4 The link between atypical antipsychotics and diabetes exacerbates this risk.4-6 A recent study of 56,849 Veterans Administration patients found that 7.3% developed diabetes and 0.2% experienced ketoacidosis requiring hospitalization after 3 months of atypical antipsychotic treatment. The diabetes, however, usually took longer than a year to develop. Risk was highest with clozapine and olanzapine; risk with quetiapine and risperidone was similar to that with conventional antipsychotics. The study had significant limitations: it included an older, predominantly male population, and it did not allow for screening for concurrent medications or lifestyle issues. The results suggest that monitoring for weight gain or glucose aberrations following treatment initiation with an atypical antipsychotic can identify at-risk patients early.

Lifestyle Challenges

With relatively health-conscious individuals who develop diabetes, clinicians understandingly focus on improving diet, increasing exercise, and, if they smoke, helping them quit. Yet, even under the best of circumstances, many such individuals lack motivation to see these tasks to completion. When a person with schizophrenia develops diabetes, issues become muddier. Poor dietary habits, obesity,7,8 high rates of smoking, and the use of alcohol and street drugs are common problems among the mentally ill in general, and in schizophrenia sufferers specifically.9 Their cognitive deficits and lack of insight can hinder effective counseling. Health care provider interventions must be very specific, depending on baseline risk factors (Table 2).10,11 This is especially the case with patients who are obese and have clinically present diabetes symptoms.


Obesity is an independent risk factor for diabetes.12 Almost all antipsychotics, including the older drugs, increase obesity risk. The drugs vary markedly in this regard.13,14 Meta-analysis found that patients receiving standard doses of atypical antipsychotics for 10 weeks gained a mean of 9.79 lb with clozapine, 9.13 lb with olanzapine, 6.42 lb with sertindole, 4.6 lb with risperidone, and 0.09 lb with ziprasidone.13 Prospective studies found that the annual mean weight gain was 11.7 to 13.9 lb for clozapine, 15 to 26 lb for olanzapine, 4.4 to 5.1 lb for risperidone, and 6.1 to 12.3 lb for quetiapine. Ziprasidone and aripiprazole both had mean weight gains of less than 2 lb.4

Weight monitoring is critical. A reasonable monitoring plan includes recording the patient's body mass index (BMI) before starting or changing antipsychotics and at every physician visit during the next 6 months. Then, weighing should occur at least quarterly, or more often if weight begins to accumulate. Clinicians should show patients how to weigh themselves, and tell them to notify the prescribing physician if they gain either 5% of their baseline weight or the number of pounds that corresponds to an increase of 1 BMI unit (these figures can be calculated with or for the patient).

A consensus panel on schizophrenia and diabetes recommends interventions when a patient experiences a weight gain of 5% or greater anytime during the course of treatment.4,11 Interventions may include nutritional counseling for the patient, caregiver, or food preparer, as well as a tailored exercise program, and/or medications promoting weight loss. The prescriber might consider using an antipsychotic medication associated with less weight gain at this point, but, admittedly, the prescriber may have a clinical dilemma with patients who have improved significantly except for weight gain.

Glucose Monitoring

When antipsychotic agents are started or changed, clinicians should monitor FPG levels. Often, people with schizophrenia are not capable of fasting reliably. In those cases, measuring hemoglobin A1C is acceptable. FPG levels of >126 mg/dL, random plasma glucose levels of >200 mg/dL, or hemoglobin A1C levels of >6.1% should trigger more frequent follow-up.12

Pharmacists can help people with schizophrenia learn about the clinical symptoms of diabetes (polyuria, polydipsia, a prediabetic FPG in the range of 100 to 125 mg/dL, and a weight change) and might ask about these symptoms during counseling. Should diabetes develop or be present, pharmacists should encourage consultation with an internist or other primary health care provider for further assessment. They also should collaborate with patients to increase adherence to any prescribed medications.


It is well-documented that cardiovascular disease is linked to elevated cholesterol and triglyceride levels. Treatment guidelines encourage aggressive lipid-level reduction, using lifestyle changes and lipid-lowering agents. Although patients with schizophrenia have a high risk for coronary heart disease (CHD), they may be less likely than other individuals to receive lipid-lowering medications.15 Expert consensus panels recommend monitoring lipid profiles according to guidelines established for patients at increased risk for CHD. The recommendations of the National Cholesterol Education Program16 and those of the US Preventive Services Task Force17 can be used, but the latter may be easier to implement in psychiatric settings.12 Those guidelines suggest screening and treating men aged 20 to 35 years and women aged 20 to 45 years who possess increased risk for CHD. Schizophrenia patients in general may be considered to be at high risk for CHD and should be screened routinely beginning at age 20.


Patients who have schizophrenia may have limited insight into their medical health risks, or they may have poor access to primary care providers. Pharmacists often see these patients more frequently than physicians do. Thus their assistance may be valuable in monitoring the different types of care needed or received, as well as the health risks associated with antipsychotic medications. Improving the clinician-patient relationship (called "therapeutic alliance" in psychiatry circles) can improve adherence to treatments.18 Actively engaging persons with schizophrenia as partners and collaborators can improve their lives?and lengthen them.

Dr. Zanni is a psychologist and health-systems consultant based in Alexandria, Va. Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Bethesda, Md. The views expressed in this article are those of the authors and not necessarily those of any government agency.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.

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