Obesity and depression are two of the most pressing public health challenges.

Globally, more than 280 million people live with depression, and 890 million adults live with obesity. When the conditions coexist, the challenge for clinicians becomes how to manage both successfully at the same time.

The relationship between the two conditions is likely bidirectional, experts agreed, and shared biological, psychological, and social pathways put patients at risk for both.

A patient with major depressive disorder has a 71% increased risk of developing obesity compared with someone who does not have that mental health diagnosis, according to a new report in The Lancet. People living with obesity have a 32% increased risk of developing depression compared with an individual not living with obesity.

When the conditions overlap, and clinicians need to manage both at once, where can they turn?

No Formal Guidelines for Comorbid Obesity, Depression

Unfortunately, they cannot turn to formal guidelines to address both at once because they do not exist.

While separate guidelines abound for obesity and for major depressive disorder, these same organizations, from obesity organizations to psychological, “don’t offer specific recommendations for those with both conditions,” said Pamela Kushner, MD, a clinical professor of family medicine at the University of California Irvine Medical Center in Orange, California. She co-authored a 2025 review of the literature and offered recommendations on treating obesity in patients with depression.

The Lancet reviewers agreed. Despite the high prevalence of major depressive disorder with comorbid obesity, there are no clinical guidelines for monitoring and managing this patient group, they wrote.

But these two recent literature reviews, along with another published this year from the Cleveland Clinic, do offer preliminary guidance on how to manage the conditions when they overlap. Here, some highlights of their recent reviews, along with additional input from the authors.

Lancet: A Risk Stratification and Monitoring Framework

It’s crucial for clinicians to recognize the double stigma patients may encounter when they are living with both obesity and depression, wrote co-author Nils Opel, MD, a psychiatrist at Charité-Universitatsmedizine Berlin in Berlin, Germany.

Guilt, shame, and helplessness are common, he said, leading people to put off doctor’s visits or skip them altogether. Psychiatrists might be the only point of contact for the patients, so they may have a role in not only mental health but also physical and metabolic health, the researchers wrote. Among their suggestions:

• Systemic screening is needed, including metabolic, lifestyle assessment; psychiatric evaluation; and assessment of demographic and psychosocial risk factors. It’s crucial to rule out underlying conditions, such as Cushing syndrome and obstructive sleep apnea, and other conditions. Metabolic assessment can include not only BMI but also assessment of waist circumference or waist-to-hip ratio.
• Ongoing monitoring is needed for obesity, metabolic dysregulation, poor lifestyle habits, body weight gain during a depressive episode, and treatment-resistant major depressive disorder. Poor diets, especially those high in simple sugars and processed snacks, raise the risk for weight gain and metabolic disturbances. Emotional eating is a frequent, and harmful, coping method. With the high risk for complications in this population, ongoing monitoring of changes in depressive symptoms and metabolic health is necessary.
• Treatment strategies include psychotherapy, antidepressant drugs, physical exercise, dietary interventions, and metabolic drugs. Research suggests that serotonergic medications are less efficient in these patients than those acting on noradrenergic or dopaminergic pathways. As an example, they wrote, higher response rates have been reported in those on selective serotonin reuptake inhibitors (SSRI) combined with adjunctive bupropion and in those treated with venlafaxine compared with SSRI alone.
• Whether the GLP-1 medications for weight loss may help depressive symptoms or worsen them is often discussed on social media, and the focus of this study that found differing opinions. Scientific evidence is scarce.

Needed: A Holistic Treatment Plan

With the overlap in the pathways underlying both diseases, a holistic treatment plan is needed, Kushner and her colleagues concluded.

Among their practical suggestions:

• Systemic inflammation is associated with depression, and obesity is linked with depression symptoms, such as fatigue and low energy.
• Primary care physicians should regularly screen patients for obesity and screen patients with obesity for depression.
• When considering treatment options for both conditions, consider how the interplay may affect treatment success. For instance, weight gain occurs with some antidepressants, so this must be taken into account. A table in their review lists numerous antidepressant options but only five with neutral weight effects or weight loss (bupropion, dextromethorphan-bupropion, esketamine, fluoxetine, and zuranolone). Likewise, anti-obesity medications have varying results, with losses of 5% to more than 20% produced.

If an antidepressant is indicated, “choose one that does not cause weight gain,” Kushner said in an interview with Medscape Medical News. While that may seem like common sense, she said, “I see so many patients on antidepressants known to cause weight gain.”

Kushner encourages her fellow primary care doctors to bring up the weight conversation. “Many clinicians are afraid to discuss obesity with their patients,” she said. They’re concerned, she said, about hurting patients’ feelings, “so they don’t even ask.” In her 30 years of primary care practice, she said, she is sure that approach is misguided. “They want to talk about it.”

Besides helping patients with obesity talk about their weight, and devise a plan, she said, it’s crucial to ask patients with obesity, especially women, about any history of childhood trauma, such as sexual and physical abuse. Numerous studies have found an association.

Treat Depression First?

In a review of recent studies on the interaction between obesity and depression, Cleveland Clinic researchers said research suggests treating depression first when both conditions occur together is beneficial.

Both conditions are pervasive and costly to treat, they noted, and are likely interacting to worsen patient outcomes.

Among the many mediating factors between obesity and depression, research suggests, is emotional eating.

Cognitive-behavioral therapies aimed at comorbid obesity and depression have demonstrated effectiveness, their review found. While weight loss didn’t improve in a 1-year study of cognitive-behavioral therapy, for instance, depression did, and improvement in depression is linked with weight loss.

“For most patients, depression and obesity can be treated concurrently, as improvement in one arena often have a positive effect on the other,” co-author Leslie J. Heinberg, PhD, vice chair of psychology at Cleveland Clinic, Cleveland, told Medscape Medical News.Depending on severity, however, one condition may need to be prioritized, she said. While a patient with severe depression may need psychiatric treatment first, a patient with very severe obesity may need interventions such as bariatric surgery first, for instance.

Successful Comanagement

Heinberg recalled an example of comprehensive care that produced good results. A patient, in his late thirties, had class III obesity and major depression, generalized anxiety disorder, binge eating disorder, and posttraumatic stress disorder.

The patient’s primary care clinicians prescribed an SSRI, tricyclic antidepressant for sleep, atypical antipsychotic for augmentation, and hydroxyzine. The patient had difficulty making changes to diet and had no insurance coverage for an injectable GLP-1.

“After a comprehensive evaluation by obesity medicine, psychology, and a dietitian, the patient was referred to a psychiatrist for a full evaluation and a number of less obesogenic medications were prescribed,” Heinberg said. The patient reported improved mood and started psychotherapy, also receiving group treatment for binge eating along with consultation from nutrition experts and initiation of naltrexone-bupropion.

Within a few months, improvement in mood continued, binge eating episodes remitted, and a 10% weight loss had occurred, Heinberg said.

Opel and Heinberg reported no disclosures.

Kushner reported receiving consulting fees from Abbott, AstraZeneca, Corcept Therapeutics, GSK, Haleon, Lilly/Boehringer Ingelheim, Novo Nordisk, and Salix Pharmaceuticals; honoraria from Bayer, Corcept Therapeutics, GSK, Haleon, Janssen, Lilly/Boehringer Ingelheim, and Phathom Pharmaceuticals; travel support from A2 Biotherapeutics, Corcept Therapeutics, Currax Pharmaceuticals, LLC, GSK, Haleon, Janssen, Lilly/Boehringer Ingelheim, and Phathom Pharmaceuticals; and medical writing support from Haleon and reported holding stock or stock options in Abbott.