Diabetes and depression


Which comes first, diabetes or depression? While the connection is recognized, the answer is not yet certain.

The interrelationship between depression and diabetes is only now being studied and understood. It can almost seem like a chicken-and-egg question. Which comes first? Do symptoms of depression predate those of diabetes, or are the very early stages of diabetes causing depression?

The situation becomes even more complicated when you consider the adverse effects that some antidepressant medications have on body weight and blood glucose levels. Treating depression with medications can put some patients into pre-diabetes or move them from pre-diabetes into full-blown diabetes.

Tracing the connection

In the past several months, several papers have been published that examined the interplay between diabetes and depression.

Depression is seen twice as often in people with type 2 diabetes as it is in the general population, but no similar increased incidence is seen in type 1, said Paula M. Trief, PhD, senior associate dean for faculty affairs and faculty development, and professor in the Departments of Psychiatry and Medicine at the State University of New York Upstate Medical University in Syracuse.

“People who have diabetes and depression have poorer diabetes-related outcomes,” she said. “They have poorer glycemic control, more complications, higher mortality, and higher costs.” 

Trief was the lead author on a study that screened more than 6,000 patients with type 1 diabetes and found that between 4.6% and 10.3% had signs of major depression. Those who were found to be depressed tended to have worse clinical outcomes; they were more likely to exercise less often, to miss insulin doses, and to experience more complications.1


A major public health problem

This August, the National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with the National Institute of Mental Health and the Dialogue on Diabetes and Depression, published a report on the subject.

“Shared biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, autonomic dysfunction, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors, are important to consider in understanding the link between depression and diabetes,” the report stated. The report called the association between diabetes and depression or depressive symptoms a major public health problem.2

Symptoms and likelihood

Data from the Black Women’s Health Study, a large prospective study, found that both depressive symptoms and the use of antidepressant medications were associated with a later diagnosis of diabetes. The data was collected from 1999 through 2011 on almost 36,000 women who did not have a diagnosis of diabetes to begin with. The association between depressive symptoms and later diabetes was stronger with women with higher numbers of depressive symptoms.3

Research using data from the South London Diabetes Study found an association between depressive symptoms and systemic inflammation in people who were newly diagnosed with type 2 diabetes. The study, which was based on nearly 1,800 patients, concluded that increased inflammation might be involved in the pathogenesis of depressive symptoms in type 2 diabetes.4

A prospective study from 2011 used data from the Women’s Health Initiative on postmenopausal women. It found that women who had symptoms of depression and who took antidepressants had a greater risk of developing diabetes later on. This study followed nearly 162,000 women for an average of 7.6 years.5

 “Pharmacists and other healthcare providers are aware of this growing body of evidence that has established a connection between diabetes and depression,” said Charlene Williams, Pharm.D., BCACP, CDE, Western Experiential Education Coordinator  and clinical assistant professor at the University of North Carolina’s Eshelman School of Pharmacy in Asheville. Williams helps place pharmacy students for their advanced practice experience in western North Carolina.


Search for the cause

Even with many new findings about diabetes and depression coming out, it is hard to know what is causing the interplay between diabetes and depression. The two conditions are connected, but one may not necessarily predate the other. “The association between diabetes and depression appears to be bidirectional,” Williams said.

“Part of the issue is what comes first? People who have diabetes and have high blood sugar levels - their symptoms are fatigue and a feeling of not wanting to do anything, and lack of enjoyment because they just don’t feel good,” said Marjorie Cypress, PhD, CDE, a nurse practitioner in a group practice in Albuquerque, N.M., and 2014 president of healthcare and education for the American Diabetes Association in Washington, D.C.

Stress and depression can raise levels of cortisol in the body, Cypress noted. Elevated cortisol levels can increase a person’s desire for foods with a lot of calories and sweet foods. “This alters the metabolism and promotes the accumulation of visceral fat,” she said.

Depression also makes people want to be less physically active, which also leads to added body weight and elevated blood sugar levels, she added.

Some antidepressants may be associated with diabetes, because treatment of the depression has caused patients to gain weight, Cypress said. “Did we start this person on antidepressants and then they developed diabetes, or were they already at high risk?”

Depression is more prevalent in people with type 2 diabetes than it is in the general public. It is also more common in people with other chronic illnesses, such as stroke and heart disease, said Trief. The rate of depression in people with diabetes has not been compared to the rate of depression seen with other chronic diseases.

“There is a connection between depression and diabetes, but whether it is unique to diabetes or is connected in other types of chronic illness, we don’t know,” she said.


Diabetes distress

Diabetes is a complex and progressive condition. It requires considerable intensive self-care and many life changes. Receiving a diagnosis of diabetes, especially in adulthood, can add significant stress and disruption to everyday life, Cypress pointed out.

Some people in the diabetes community have started to talk about “diabetes distress,” said Cypress. “Maybe what we are calling depression is the distress of having diabetes.”

“I sometimes talk to people about it as being a loss, the loss of their self-concept of being a healthy person,” she said.

Helping patients cope with their disease can help their distress, Williams said. “Interventions that assist patients with self-care management may improve depressive symptoms.  Early intervention may prevent more severe depressive symptoms from emerging later.”

Diabetes and antidepressants

Choosing the right medications for depression for a patient with diabetes can be tricky.

“The hope is that an effective treatment for depression will help improve some of the other triggers for diabetes,” Williams said. “In many cases, patients will become more active and their nutritional habits will improve when their depression is improved.”

Several medications used to treat depression can have an adverse effect on metabolism, either by affecting blood glucose levels or by contributing to weight gain, which in turn can increase insulin resistance. Pharmacists are familiar with the adverse effect profiles of these drugs, which puts them in an excellent position to educate patients about possible risks, as well as to work collaboratively with other providers to optimize medication regimens, Williams said.

Antidepressants that may adversely affect body weight or blood glucose levels include atypical antipsychotic drugs, which are increasingly being used as adjunctive therapy in treating depression, Williams said. Ariprazole and ziprasidone may have less of an adverse effect. Tricyclic antidepressants are also associated with weight gain and hyperglycemia, she added. Monoamine oxidase (MAO) inhibitors are not used as commonly for depression as they once were, but they can cause weight gain, she noted. 

Selective serotonin reuptake inhibitors (SSRIs) are thought to improve glycemic control, but there is little data on their long-term use, Williams said.

“Some evidence suggests that longer duration of treatment and higher doses of antidepressants could be linked to worsened glycemic control,” she said, adding that she usually avoids recommending paroxetine and mirtazapine because of weight-gain issues.

However, even drugs that have a lower risk of causing weight gain or glycemic issues - the drugs that are thought of as better choices for people with diabetes - may still cause problems.  “I have seen a few patients who have been put on one of those drugs, who say they have gained 20 to 30 pounds,” Cypress said.


Other treatments

Medications are not the only choice to consider when dealing with diabetes and depression comorbidity, especially in the area where depression and diabetes distress overlap. Patients with diabetes distress who are showing symptoms of depression can be helped with educational and support programs.

A recent study divided a group of type 2 diabetes patients showing high rates of depressive symptoms into three groups that received different interventions for a year. One group was enrolled in an online diabetes self-management program; a second group, enrolled in the same program, received individualized assistance to help them solve problems related to their diabetes; and the third group was given personalized information about their health risks and sent educational materials by mail. All patients also received personal phone calls during the study.

All three intervention strategies significantly reduced distress levels and symptoms of depression.6

Screening tools

The American Diabetes Association recommends that all patients with diabetes be screened for depression regularly. Screening for depression is not onerous and is something that pharmacists can do in the course of counseling a patient with diabetes.

Several versions of the Patient Health Questionnaire can be used in a pharmacy setting and quickly administered. The PHQ 9 has just nine questions. There is also the even briefer PHQ 2, which asks only the first two questions on the PHQ 9: “Are you bothered by having little interest or pleasure in doing things? Are you feeling down, depressed, or hopeless?” 

“In my practice, we try to screen patients for depression once a year,” Williams said. Screening is performed more often if patients seem to be having a problem, such as losing control of their condition after a period of successful self-management, she added.  

“Both the PHQ 9 and the PHQ 2 are relatively simple to administer in a variety of settings,” Williams said. “Patients whose results suggest depressive symptoms should be referred to their primary care provider.” 

A system of collaborative care for a patient, one that involves all the patient’s healthcare providers, can improve both depression symptoms and glycemic control, she added.    

Tools such as the PHQ 9 and PHQ 2 screen for symptoms of depression. Some of these symptoms may reflect diabetes distress rather than a co=morbid psychiatric disorder. There is also the PAID, the Problem Areas in Diabetes Scale, which is a measure of emotional function in diabetes, such as how well the patient is adjusting to a wide range of diabetes management situations, said Cypress. PAID is a larger questionnaire, which may mean that PHQ 9 or PHQ 2 would be easier to use in a primary care situation, she said.

Further research on diabetes and depression may clarify the relationship between the two conditions. However, it is wise for pharmacists to keep that relationship in mind when counseling and assisting their patients with diabetes.


1.     Trief PM, Xing D, Foster NC, et al. “Depression in Adults in the T1D Exchange Clinic Registry.” Diab Care. 2014; 37:1563–1572.

2.     Holt RIG, de Groot M, Lucki I, et al. “NIDDK international conference report on diabetes and depression: Current understanding and future directions.” Diab Care.  2014; 37:2067–2077.

3.     Vimalananda VG, Palmer JR, Gerlovin H, et al. “Depressive symptoms, antidepressant use, and the incidence of diabetes in the Black Women’s Health Study.” Diab Care. 2014; 37:2211–2217.

4.     Laake JPS, Stahl D, Amiel SA, et al. “The association between depressive symptoms and systemic inflammation in people with type 2 diabetes: Findings from the South London Diabetes Study.” Diab Care. 2014; 37:2186–2192.

5.     Ma Y, Balasubramian R, Pagoto SL, et al. “Elevated depressive symptoms, antidepressant use, and diabetes in a large multiethnic national sample of postmenopausal women.” Diab Care. 2011; 34:2390–2392.

6.     Fisher L: “REDEEMing Patients from diabetes-related distress.” Presented at the 74th  Scientific Sessions, American Diabetes Association, San Francisco, June 15, 2014.

Valerie DeBenedetteis a medical news writer in Putnam County, N.Y.

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