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Mental Disorders Complicate the Treatment of Patients with Diabetes

Aug 14, 2021
Editor: Steve Freed, R.PH., CDE

Author: Ashley Ball, PharmD Candidate, LECOM-School of Pharmacy

Individuals with mental health disorders have an increased risk for type 2 diabetes and premature death; modifiable risk factors affected by antipsychotics are obesity, insulin resistance, diabetes, and dyslipidemia.

Serious mental illness (SMI) is associated with premature mortality, particularly cardiovascular disease (CVD) related death. Persons with schizophrenia have an overall 3-fold increased risk of death relative to the general public. A Denmark study looked at the life expectancy among persons with schizophrenia and found that the average loss of years of life in people with SMI is 20 years relative to the general population. Seventy-five percent is from premature cardiovascular disease (CVD), including stroke and myocardial infarction. Persons with schizophrenia have two times the general population’s coronary heart disease death rate and two times the prevalence of diabetes. Recent studies from Canada and Demark reveal that while the life expectancy of the general population has consistently tracked upwards as the decades have gone by, the life expectancy for persons with SMI is decreasing.


Reasons for increased CVD mortality in people with SMI include increased modifiable health risk factors: obesity, smoking, dyslipidemia, metabolic syndrome, physical inactivity, diabetes, prediabetes, and hypertension. This population also has a decrease in the following: adherence to treatment and access to high-quality medical care. The main failure is a failure of primary and secondary prevention. They are less likely to receive a CABG or an angioplasty. A small percentage of this population receives drug therapies with proven benefit post-myocardial infarction relative to the general population. Subsequently, they are more likely to have premature mortality post-myocardial infarction.

Trials have been instrumental in showing the discrepancies in treating persons with SMI compared to the general population. A well-known trial, CATIE, revealed missed prevention opportunities. The trial unveiled low rates of treatment for metabolic disorders in participants that had schizophrenia. The RAISE trial showed that the number of SMI patients receiving treatment for hypertension, diabetes, and elevated cholesterol was less than that of the regular population.

When action has taken place, it takes long periods for change to occur. For example, the FDA warned that antipsychotic (AP) medications increase hyperglycemia and diabetes risk. The FDA statement includes that there is a potential for significant weight gain and insulin resistance. However, there was little difference in statistics until years later and the implementation of strategies.

Many factors complicate the care of SMI patients. Look at all treatments a patient is on, not just the AP agent. For instance, say a patient is put on a low-risk AP medication but then initiates over-the-counter antihistamines for allergies, or a prescription is written for antihistamines as a sleep aid. The addition of the antihistamine just put the patient from a low weight gain risk to a high weight gain risk. Or what if a physician decides that all patients requiring antipsychotic therapy will be switched from high risk to a low-risk agent? Topiramate has low risk but has fetal teratogenicity, so, it is off the table for most women of childbearing age.

What about the class generalization that 2nd generation APs cause weight gain and 1st generation do not? Despite popular belief, not just 2nd generation antipsychotics cause weight gain. Some 1st generation antipsychotics are at high risk for obesity. While olanzapine is the worst, all APs have metabolic effects on adiposity and insulin sensitivity.

So, what can be concluded from this? One, modifiable risk factors are more prevalent in AP treated patients than AP treatment naïve. Two, different AP medications have different levels of risk for adverse cardiometabolic effects, varying even within the class. And three, clinicians can modify the patient’s risk for these negative effects.


Practice Pearls:

  • The primary level of care needs to lower the risk of weight gain and diabetes for patients with SMI, including assessing AP and non-AP medications.
  • Individual treatment is essential. Treating patients with diabetes and a comorbid mental disorder is not one-size-fits-all.
  • Elevated triglycerides are often an early indicator for Metabolic Syndrome; track triglycerides during antipsychotic treatment.


DE HERT, M., COHEN, D., BOBES,. World Psychiatry, Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring, and treatment guidelines, plus recommendations at the system and individual level. World Psychiatry, 10: 138-151. https://doi.org/10.1002/j.2051-5545.2011.tb00036.x


Ashley Ball, LECOM PharmD Candidate



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