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Impact of Depression and Antidepressants on People With Diabetes

  • Authors: Christina Maybush, PharmD Candidate; Clinton W. Wright, PharmD, BCPP
  • CME / ABIM MOC / CE Released: 3/20/2023
  • Valid for credit through: 3/20/2024
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Target Audience and Goal Statement

This activity is intended for primary care physicians, endocrinologists, psychiatrists, and other clinicians including nurse practitioners, physician assistants, pharmacists, and nurses.

The goal of this activity is for learners to be better able to understand and manage diabetes with comorbid depression in collaboration with a healthcare team.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Recommended screening, management, and treatment of patients who have diabetes with comorbid depression
  • Demonstrate greater confidence in their ability to
    • Manage patients who have diabetes with comorbid depression across the healthcare team


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  • Christina Maybush, PharmD Candidate

    Virginia Commonwealth University
    College of Pharmacy
    Richmond, Virginia


    Christina Maybush, PharmD Candidate, has no relevant financial relationships.

  • Clinton W. Wright, PharmD, BCPP

    Medical Education Director, Medscape, LLC


    Clinton W. Wright, PharmD, BCPP, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Yaisanet Oyola, MD, has no relevant financial relationships.

Nurse Planner

  • Amy Bernard, MS, BSN, RN, NPD-BC, CHCP

    Senior Director, Accreditation and Compliance, Medscape, LLC


    Amy Bernard, MS, BSN, RN, NPD-BC, CHCP, has no relevant financial relationships.

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Impact of Depression and Antidepressants on People With Diabetes

Authors: Christina Maybush, PharmD Candidate; Clinton W. Wright, PharmD, BCPPFaculty and Disclosures

CME / ABIM MOC / CE Released: 3/20/2023

Valid for credit through: 3/20/2024


Impact of Depression and Antidepressants on People With Diabetes

The effect of depression and antidepressants on people with diabetes

Clinicians may compartmentalize diabetes and depression, but these 2 diseases occur together at relatively high rate. Studies show the odds of depression in people with diabetes is twice that of people without diabetes.[1] While more research is being done to understand the relationship, it has been shown that depression can be both a consequence of diabetes as well as a risk factor for developing diabetes.[2] Screening and treating depression in people with diabetes is important not only for the patient’s mental health but also for their diabetic health. While identifying patients has improved in the last decade, studies show only 51% of patients with comorbid depression and diabetes were recognized to have both, and only 31% received an adequate antidepressant dose.[3] In terms of medications, antidepressants have been shown to increase risk for developing diabetes. A recent study showed long-term antidepressant use increased the risk of type 2 diabetes onset. This study also found patients who discontinued or reduced their antidepressant dose had lower glycated hemoglobin (HbA1c) level.[4] While treatment is important, it’s equally important to choose the best treatment for each condition.

American Diabetes Association (ADA) Standards of Care (SOC) recommendation

ADA SOC recommends annual screening of depressive symptoms in people with diabetes with validated depression screening tools. Referral to mental health professionals is recommended for in-depth assessment when indicated.[5] While guidelines recommend screening all patients with diabetes annually, studies show only 11% of people with diabetes and no known history of major depressive disorder (MDD) receive annual depression screening. This is compared to about 65% of patients with diabetes who have a known history of MDD who receive annual depression screening.[6] While ADA SOC emphasize the importance of screening patients with a known history of depression, patients without a known history are underdiagnosed and therefore untreated. This study found that when all patients were screened, patients with diabetes and no known history of depression scored slightly higher on the Patient Health Questionnaire (PHQ-9) than patients with a known history of depression.[6] The PHQ-9 is a 9-item measure of depressive symptoms that is commonly used in primary care. Other screening tools include the Child Depression Inventory (CDI-2) which is used in patients ages 7-17 years and the Geriatric Depression Scale (GDS) which is used in patients ages 55 to 85 years.[7] In a recent study, PHQ-9 items were found to be similar for people with and without diabetes. While symptoms of diabetes, including trouble sleeping or low energy, may overlap with symptoms of depression, they did not impact interpretation of the PHQ-9.[8]

Understanding and managing comorbid diabetes and depression

While mortality risks are already high with diabetes alone, a study examining the mortality risk of people with diabetes with comorbid depression, anxiety, or both showed that the highest risk of death was observed in patients with diabetes and depression (Figure 1).[9]

Figure 1. Deaths in Participants With and Without Depression (DEP) and Type 2 Diabetes (T2D)[9]

Individuals in the study with diabetes and depression had a 110% increased risk of death, compared with a 66% increased risk of death associated with anxiety.[9] Identifying patients with comorbid diabetes and depression, can lead to effective treatment and improved outcomes. In a recent study, patients with uncontrolled diabetes and a diagnosis of depression were more likely to achieve glycemic control within 36 months if they received antidepressant treatment.[10]

Treatment for comorbid depression and diabetes

Studies have shown improvements in both depressive symptoms and blood glucose levels when depression and diabetes were treated simultaneously.[5] A recent study that analyzed the results of past trials on depression and diabetes proposed a flowchart to guide treatment based on the clinical profile of the patient (Figure 2).[11] This study found that interventions that were effective in MDD were not as effective in subthreshold depression, where a patient has two or more depressive symptoms but does not meet the diagnostic criteria for depression.

Figure 2. Flowchart Showing Treatment Recommendations for Comorbid Depression in Diabetes.[11]

Cognitive behavioral therapy (CBT) is a non-pharmacological therapy commonly used with depression. A recent study analyzing the results of CBT in patients with diabetes and depression showed significantly reduced HbA1c, fasting blood glucose and depression.[12] It is important to treat depression in patients with diabetes while also considering how the medication may affect the patient’s blood glucose. While there are only a few studies on tricyclic antidepressants, those studies showed increased glucose level in patients with depression and diabetes.[13] In general, selective serotonin reuptake inhibitors have shown to improved glycemic levels over placebo in several studies.[14] In addition to the type of treatment, another factor in effective treatment for people with diabetes and depression is the healthcare professionals who are providing the treatment. A recent study showed patients with comorbid diabetes and depression had statistically significant improvements in both depressive symptoms and cardiometabolic disease through collaborative care intervention, as compared to usual care.[15] In this study, “care coordinators” met with patients to address barriers to care, provided patient education, and reviewed patient cases with a diabetes specialist and a psychiatrist weekly or bi-weekly.

The importance of interprofessional healthcare teams

Compared to usual care, collaborative care was associated with significantly better depressive outcomes and adherence in patients with depression and diabetes.[16] Collaborative care improves glycemia and depression treatment response. It also improves the adherence to treatment of both oral hypoglycemic drugs and antidepressants.[14] In a recent study, patients randomized to the integrated care intervention were more likely to achieve HbA1c levels of less than 7% as well as remission of depression compared with patients in the usual care group.[17] In the study “integrated care managers” worked with physicians to provide education about depression and type 2 diabetes to improve adherence to antidepressants and antihyperglycemic medication. Additional studies have shown patient outcomes improve when nurses and pharmacists are active members of a patient's healthcare team.[18,19]

When to refer to a mental health provider

Collaborative care includes referring a patient to a mental health specialist when warranted. While a patient’s primary care provider (PCP) should perform annual depression screening and may provide care for both the patient’s diabetes and depression, referral to a qualified behavioral health provider is recommended in certain situations. Table 1 provides a summary of suggested situations for referral.[7]

Table 1. Situations That Warrant Referral of a Person With Diabetes to a Mental Health Provider for Evaluation and Treatment

  • If self-care remains impaired in a person with diabetes distress after tailored diabetes education 
  • If a person has a positive screen on a validated screening tool for depressive symptoms 
  • In the presence of symptoms or suspicions of disordered eating behavior, an eating disorder, or disrupted patterns of eating 
  • If intentional omission of insulin or oral medication to cause weight loss is identified 
  • If a person has a positive screen for anxiety or fear of hypoglycemia
  • If a serious mental illness is suspected 
  • In youth and families with behavioral self-care difficulties, repeated hospitalizations for diabetic ketoacidosis, or significant distress 
  • If a person screens positive for cognitive impairment 
  • Declining or impaired ability to perform diabetes self-care behaviors 
  • Before undergoing bariatric surgery and after if assessment reveals an ongoing need for adjustment support 


Clinical Pearls and Conclusions

Here are some practical examples of healthcare practitioners engaging with patients who may be at risk for both depression and diabetes:

  • A patient is visiting his primary care provider’s office for a routine visit related to his diabetes. The nurse notes that he walks slower than usual to the exam room, is forgetful regarding what medicines he takes, and he is 10 pounds lighter than his last visit 3 months ago. She asks him to fill out a PHQ-9 in the exam room while waiting for his nurse practitioner.
  • A patient asks her pharmacist about several somatic complaints including difficulty sleeping for which she would like an OTC product. She is known to him for having diabetes and depression. The pharmacist checks her profile and she is on a low dose of a SSRI. Before the patient leaves, he asks to speak to her. She relates that the antidepressant is not really doing anything. He states that some of her somatic/sleep complaints may be related and suggests that she discuss this with her endocrinologist at an appointment next week.
  • A primary care physician who has patients complete a PHQ-9 at every visit sees a middle age, obese patient whose score suggests a diagnosis of depression. After further exploration by the PCP, it is determined that the patient meets criteria for MDD. In addition to starting him on an antidepressant, he orders labs to check a random blood glucose level and his HbA1c.

Understanding how depression and antidepressants affect diabetes is important to ensure patients receive optimal care. Screening patients with diabetes, monitoring medication efficacy and side effects, and referring to mental health professionals are some of the ways healthcare professionals can work together to increase positive outcomes in patients with comorbid depression and diabetes.

This transcript has been edited for style and clarity.

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