Reducing morbidity and mortality from common medical conditions in schizophrenia

Diagnosis. All patients with schizophrenia should be evaluated for undiagnosed diabetes. The diagnosis of T2DM is made by documenting:

• a fasting plasma glucose reading of ≥126 mg/dL
• symptoms of T2DM, along with a random plasma glucose reading of ≥200 mg/dL
• 2-hour reading of a plasma glucose level >200 mg/dL on an oral glucose tolerance test.

Recent guidelines also suggest using a hemoglobin A_1c value cutoff of ≥6.5% to diagnose T2DM.

In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, 38% of patients with schizophrenia and diabetes were not receiving any treatment for T2DM.¹⁵

Risk factors for T2DM are:

• BMI >25
• a first-degree relative with diabetes
• lack of physical activity
• being a member of a high-risk ethnic group (African American, Hispanic American, Native American, Asian American, or Pacific Islander)
• having delivered a baby >9 lb or having had gestational diabetes
• hypertension
• high-density lipoprotein (HDL) cholesterol level of ≤35 mg/dL
• triglyceride level of ≥250 mg/dL
• history of an abnormal glucose tolerance test
• history of abnormal findings on a fasting plasma glucose test
• history of vascular disease.

Early detection and management.

• Educate the patient and family about signs and symptoms of T2DM, such as polyuria, nocturia, polydipsia, fatigue, visual disturbances, and (in women) vulvitis. Also, psychiatrists should be aware of, and inquire about, symptoms of diabetic ketoacidosis.
• At the start of therapy with any antipsychotic, particularly a second-generation antipsychotic (SGA), ask patients about a family history of diabetes and measure the hemoglobin A_1c value.
• Monitor the hemoglobin A_1c level 4 months after starting an antipsychotic, then annually, in a patient with significant risk factors for diabetes.
• Monitor blood glucose every 6 months in patients with no change from initial results and more frequently in those with significant risk factors for diabetes and those who gain weight.
• Order a lipid panel and measure the serum glucose level to rule out dyslipidemia and diabetes, because a patient with high lipid levels and diabetes is at higher risk of developing cardiovascular conditions.
• Advocate for smoking cessation.
• Switch to an antipsychotic with a lower risk of diabetes when clinically appropriate, such as switching a patient from olanzapine or high-dose quetiapine to a high- or medium-potency typical antipsychotic (such as haloperidol or perphenazine), ziprasidone, aripiprazole, iloperidone, and lurasidone (Table 2).
• Consider prophylactic use of metformin along with antipsychotics. Metformin has been used to improve insulin sensitivity and can lead to weight loss in diabetic and non-diabetic patients. The drug has modest potential for offsetting weight gain and providing better metabolic control in overweight outpatients with schizophrenia.¹¹ Metformin is simple to use, does not lead to hypoglycemia, does not require serum glucose monitoring, and has a favorable safety profile.¹¹
• Educate the patient about modest physical activity. For example, a 20-minute walk every day reduces the risk of cardiovascular disease by 35% to 55%.⁶
• Refer the patient to a dietitian to develop an appropriate diet plan.
• When diabetes is diagnosed, ensure appropriate follow-up and initiation or continuation of therapy with a general practitioner or an endocrinologist.
• Reinforce the need for ongoing follow-up and compliance with therapy for diabetes.

Hyperlipidemia and dyslipidemia
Elevated cholesterol and triglyceride levels are associated with cardiovascular diseases, such as ischemic heart disease and myocardial infarction. A 10% increase in cholesterol levels is associated with a 20% to 30% increase in the risk of coronary artery disease; lowering cholesterol by 10% decreases the risk by 20% to 30%.¹⁶ Triglyceride levels ≥250 mg/dL are associated with 2-fold higher risk of cardiovascular disease.¹⁶

The incidence of dyslipidemia is not as well studied as diabetes in patients with schizophrenia. There is increased prevalence of dyslipidemia in patients with schizophrenia compared with the general population because of obesity, lack of physical activity, and poor dietary habits.¹⁶

Data regarding the effects of first-generation antipsychotics (FGAs) on lipid levels are limited, but high-potency drugs, such as haloperidol, seem to carry a lower risk of hyperlipidemia than low-potency drugs, such as chlorpromazine and thioridazine.¹⁷ A comprehensive review on the effects of SGAs on plasma lipid levels suggested that clozapine, olanzapine, and quetiapine are associated with a higher risk of dyslipidemia¹⁷ (Table 2).

In the CATIE study, olanzapine and clozapine were associated with a greater increase in the serum level of cholesterol and triglycerides compared with other antipsychotics, even after adjusting for treatment duration. Furthermore, a retrospective chart review of patients who switched to aripiprazole from other SGAs showed a decrease in levels of total cholesterol and low-density lipoprotein cholesterol¹⁵ (Table 2).

Patients with schizophrenia are more likely to have dyslipidemia go undiagnosed, and therefore are less likely to be treated for the disorder. In the CATIE study, 88% of patients with dyslipidemia were not receiving any treatment.¹⁵