12/5/17

Pick Your Poison: Diabetes and Psych Meds

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The American Diabetes Association said 30.3 million Americans, 9.4% of the population, had diabetes in 2015. There are 1.5 million news cases of diabetes diagnosed each year. It is the 7th leading cause of death in the U.S. with 79,535 death certificates in 2015 listing it as the underlying cause of death. A total of 252,806 death certificates listed diabetes as an underlying or contributing cause of death. If the number of deaths from diabetes were equal to 252,806, it would be the third leading cause of death in the US, according to the CDC … and psych meds increase the risk for diabetes.

SSRIs have been associated with an increased risk of diabetes, as Yoon et al. noted in “Antidepressant Use and Diabetes Mellitus.” The researchers ruled out depression itself as a potential confounding variable in the relationship between antidepressants and diabetes. Their findings suggested that antidepressant drug treatment and not the depression increased the risk of diabetes mellitus (DM). “Given the widespread use of antidepressants, the implications of the increased risk are serious.”

The authors noted that while there is disagreement as to the reason for the association between antidepressant use and DM risk, some studies “propose that antidepressants may bio-pharmacologically affect glucose homeostasis and insulin sensitivity.” In “Use of Antidepressants Linked to Diabetes,” Peter Simons of Mad in America noted a study that has supported that hypothesis. A study led by Raymond Noordam and published in The Journal of Clinical Psychiatry, found the use of SSRIs in nondiabetic participants was associated with lower insulin secretion and an increased risk of insulin dependence in type 2 diabetes in older adults.

It is biologically plausible that SSRIs decrease insulin secretion and that this might, therefore, be a mechanism underlying the previously observed association between SSRIs and increased risk of type 2 diabetes. Consequently, type 2 diabetes patients treated with SSRIs might also have a higher risk to develop insulin dependence, a condition associated with an increased risk of mortality.

The researchers also found that participants already diagnosed with diabetes who were taking antidepressants were twice as likely to start insulin treatment than those who did not take antidepressants. They said: “our data might suggest that progression of type 2 diabetes during the use of SSRIs is accelerated.” Simons commented how the higher mortality rate for individuals who require insulin treatments made this “a particularly alarming finding.”

This new study provides additional convincing evidence that although SSRIs are commonly believed to have fewer risks of adverse effects than TCAs, they still carry significant risk. This appears to be particularly relevant when it comes to patients with diabetes. Whenever antidepressant medication is considered, patients and prescribers should carefully weigh the potential risks and benefits.

There was an updated meta-analysis published in PLos One, “The Risk of New-Onset Diabetes in Antidepressant Users.” Their meta-analysis found an increased risk factor of 1.27 between exposure to antidepressants and new-onset diabetes. When they restricted the analyses to higher quality studies, the relative risk was higher. The researchers noted their findings were in line with tow previous meta-analyses that reported “a 1.5-fold increase of diabetes among AD [antidepressant] users.” In an interview with Endocrinology Advisor, the lead investigator of the study extrapolated that given a 13% prevalence rate of antidepressant use in the US, a 1.3-fold increase in diabetes risk would translate to over 1 million cases of diabetes that could be due to concurrent antidepressant use.

Pharmacy Times reported in “Atypical Antipsychotic-Induced Type 2 Diabetes” that patients with schizophrenia were at an increased risk of developing metabolic disorders like type-2 diabetes mellitus (T2DM). Schizophrenic patients had a number of risk factors for T2DM, including family history, increased body mass index (weight gain), a sedentary lifestyle and the use of atypical antipsychotics. There have been several proposed mechanisms for the association of diabetes and atypical antipsychotics, one being the weight gain associated with the medications.

A 2006 study by Alvarez-Jiménez et al. found that 78.8% of patients taking atypical antipsychotics experienced a weight gains greater than 7%, the cut off for clinically meaningful weight gain in the study. In 2004 the FDA required a warning be placed in the medication guides of all atypical antipsychotics warning of the increased risk of hyperglycemia and diabetes.

 Patients with schizophrenia are at increased risk of developing metabolic disorders like type 2 diabetes. This is due to a number of factors, including the treatment of schizophrenia with atypical antipsychotics. There are several potential mechanisms behind antipsychotic-induced diabetes, including the weight gain associated with these medications, the effects on pancreatic receptors and/or glucose transporters, or some other cause not yet discovered. Most likely, it is a combination of these effects. Of the atypical antipsychotics, clozapine [Clozaril] and olanzapine [Zyprexa] are associated with the highest incidence of metabolic dysfunction, whereas ziprasidone [Geodon] and aripiprazole [Abilify] are considered to be the least risky.

In “Antipsychotic-Induced Diabetes Mellitus” published in U.S. Pharmacist, Chhim et al. reported there are several metabolic consequences with antipsychotic use, including weight gain, hyperglycemia (abnormally high blood glucose) and dyslipidemia (an abnormal amount of triglycerides, cholesterol and/or fat phospholipids in the blood). The association of type 2 diabetes mellitus (T2DM) and antipsychotic use is supported by retrospective epidemiologic studies as well as post-marketing assessment. Data indicate the prevalence of diabetes and obesity is 1.5 to 2 times higher in people diagnosed with schizophrenia or affective disorders than the general population.

The authors noted that diabetes was reaching epidemic proportions worldwide, and the contributions of medications to the development of hyperglycemia and other metabolic problems was getting more attention.  “Pharmacists are in a unique position to counsel and encourage appropriate self-monitoring in patients receiving certain drugs, such as antipsychotics, that can contribute to the development of weight gain, hyperglycemia, and dyslipidemia.” They can encourage patients to report adverse events to other health care providers and seek therapeutic substitutions, counseling, and/or treatment for the adverse events.

Another resource addressing these concerns, one that was cited in “Antipsychotic-Induced Diabetes Mellitus,” is the “Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes.” This is a joint consensus statement from the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity to help reduce the risk of developing diabetes, cardiovascular disease, and other complications of diabetes.

There was a large longitudinal study done in Denmark by Rajkumar et al. that found in addition to the high risk for diabetes conferred by schizophrenia on individuals, “the risk is further increased by both first-generation and second-generation antipsychotics.” Reporting on the study for Mad in America, Bernalyn Ruiz said the authors said the prevalence of diabetes was 4 to 5 times greater in people diagnosed with schizophrenia. “After adjusting for potential confounders, the risk was elevated threefold compared to those without a schizophrenia diagnosis.” No differences were seen between first-generation and atypical antipsychotics.

This large nationwide study confirmed endogenous risk for diabetes among individuals diagnosed with schizophrenia, with risks increasing significantly when antipsychotics are prescribed.

The bottom line is that in addition to their other adverse effects, there is credible scientific evidence that antidepressants and antipsychotics increase the risk of diabetes among individuals taking them. So when you’re advised to use one of these classes of psychiatric medications, it’s a bit like being asked to pick your poison.