Pharmacists Help Navigate Comorbid Depression and Diabetes

The comanagement of diabetes and depression presents a significant clinical challenge that pharmacists are uniquely positioned to address within integrated care models, according to Kathleen Vest, PharmD, BCACP, CDCES, FCCP, professor of pharmacy practice and clinical pharmacist at Midwestern University. Vest and Sarah E. Grady, PharmD, BCPP, BCPS, professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences, presented at the American Society of Health-System Pharmacists Midyear Clinical Meeting and Exhibition 2025.

Diabetes is a pervasive condition, impacting almost 12% of the US population—approximately 38.4 million people—and driving health care costs exceeding $400 billion annually, Vest said. Individuals living with diabetes are at least twice as likely to develop depression compared to the general population, highlighting a crucial clinical intersection.

“In the literature there's a lot of talk about depression and diabetes in a bidirectional relationship,” Vest said. "Pre-existing depression can increase the risk of type 2 diabetes, whereas also type 1 or type 2 diabetes can increase the risk of depression."

Given that pharmacists frequently encounter patients navigating both chronic disease states and mental health concerns in ambulatory or primary care settings, integrating mental health monitoring into routine practice is essential for optimizing health-related quality of life and outcomes. The ultimate goal is to move away from treating these issues in silos and combine effective diabetes and depression treatments concurrently for the best patient results.

Mental Health Screening as Part of Diabetes Care

The first step in integrated care is distinguishing between clinical depression and common diabetes distress, which is emotional distress that arises purely from the burdens of living with and managing the condition. Diabetes management is inherently overwhelming due to constant monitoring, frequent appointments, managing comorbidities like neuropathy or chronic kidney disease, and dealing with food concerns. Diabetes distress is related to coping and can manifest as being burned out or worrying about outcomes, and it can occur even if the patient's diabetes is otherwise well-controlled.

In contrast, a diagnosis of major depression requires a person to experience at least 5 key symptoms, including either depressed mood or anhedonia, which persist nearly every day and significantly affect their ability to function in daily life, such as missing work. Pharmacists should consider using validated screening tools, such as the Patient Health Questionnaire with 2 questions, which quickly assesses for these 2 core symptoms—depressed mood and loss of interest—to introduce the mental health conversation. Screening for mental health conditions is recommended at least annually for all patients with diabetes and should occur more frequently if the patient experiences a recent stressor, a significant life change, or develops a new complication related to their condition.

Treatment Options for Comanagement of Conditions

Alongside pharmacological management, lifestyle adjustments are vital, with evidence suggesting that exercise and healthy eating should be encouraged not just for glucose control but also for improving mood and depression symptoms. This connection is supported by neurochemical theories suggesting that insulin resistance may reduce levels of brain-derived neurotrophic factor (BDNF), a factor protective in mental health related to emotional regulation. Physical activity and healthy nutrition, conversely, can increase BDNF.

When pharmacological intervention is necessary, the selection of an antidepressant requires careful consideration of its effects on glucose and body weight, and current literature recommends that hemoglobin A_1C levels should be regularly monitored in patients initiating antidepressant therapy. Weight gain is a concern with many agents, thought primarily to be driven by histamine antagonism and blocking the 5HT2C receptor, which stimulates appetite. Agents associated with high weight gain risk include citalopram, mirtazapine, and paroxetine, while bupropion and fluoxetine are often neutral or associated with weight loss.

The impact of antidepressants on glucose metabolism is varied. Although there is mixed data, hypoglycemia has been reported with selective-serotonin reuptake inhibitors (SSRIs), particularly when administered alongside sulfonylureas, Grady mentioned. Conversely, specific SSRIs, such as fluoxetine and escitalopram, have been shown to potentially improve glucose control by enhancing serotonergic receptor-induced insulin sensitivity. Traditional agents like tricyclic antidepressants (TCAs) are associated with weight gain and may detrimentally affect glucose by weakening insulin release and inducing glycogenolysis.

“TCAs, we know and we've discussed already, they are associated with weight gain,” Grady said. “They can also induce glycogenolysis, and we think that this is due to really the noradrenergic reuptake inhibition.”

Serotonin-norepinephrine reuptake inhibitors are generally considered to have a more neutral effect on blood glucose. When selecting an antidepressant, pharmacists should individualize therapy based on comorbidities; for instance, duloxetine is often chosen for patients suffering from depression concurrent with diabetic neuropathic pain. However, if a patient has elevated liver enzymes, desvenlafaxine may be a more liver-friendly option compared to duloxetine. It is crucial to remember that certain medications, such as bupropion, are contraindicated in patients with a history of seizures.

Furthermore, the introduction of glucagon-like peptide-1 (GLP-1) receptor agonists represents an exciting area for managing both diabetes and related mental health issues, given their effectiveness in addressing diabetes and obesity. Initial studies suggest these agents may hold promise in the mental health realm, potentially exerting neuroprotective, anxiolytic, and antidepressant effects, possibly by enhancing synaptic plasticity and increasing BDNF.

However, as the FDA and European medicine agencies are monitoring the safety of these agents, particularly when used for obesity, pharmacists must counsel patients regarding the potential for suicidal thoughts or changes in mood. Although a causal link has not been established and some studies show a similar risk of suicidal behavior compared to placebo, monitoring is essential.

“It’s very important to ensure we don't abruptly discontinue these medications because there are so many benefits in treating their other conditions,” Grady said.

Finally, for patients using technology to manage their diabetes, pharmacists should be aware that continuous glucose monitors (CGMs) can sometimes heighten stress and anxiety, especially when incessant alerts confirm chronically high blood sugar readings. Practical strategies include adjusting the high alert threshold to reduce unnecessary beeping and subsequent anxiety.

Ultimately, if a CGM significantly impairs a patient's mental well-being, their wish to temporarily revert to traditional monitoring should be respected. Successfully managing these complicated cases requires a collaborative approach involving pharmacists, behavioral health specialists, and diabetes educators to improve patient outcomes. By routinely screening, individualizing therapy, and closely monitoring patients after any changes, pharmacists serve as essential members of the interdisciplinary team.

"We think there [are] a lot of silos in practice," Vest said. “Our goal is to really combine these topics so that we can adequately treat both concurrently for the best outcomes."

REFERENCES

Vest K, Grady S. Managing the Highs and Lows of Co-Morbid Depression and Diabetes. ASHP Midyear Clinical Meeting and Exhibition 2025. December 7-10, 2025. Las Vegas, Nevada