Somatic Cancer Symptoms May Be Overattributed to Depression

It’s not easy to discern somatic symptoms of cancer from physical manifestations of depression, according to mental health and oncology professionals.

For one thing, these somatic symptoms overlap considerably. However, a new study among women with ovarian cancer suggests that depression is overdiagnosed in this population, and that patients are missing out on more effective therapies when their complaints are routinely attributed to behavioral health.

Shortly after their ovarian cancer diagnosis, women in the study reported experiencing more somatic issues at lower levels of depression than people in the general population. Additionally, most symptoms had resolved at 1 year post-cancer diagnosis, suggesting they were caused by the cancer and not by ongoing depression, lead study author Rachel Telles, MA, told Medscape Medical News.

It’s worth taking the time to talk to patients about their symptoms to determine their cause, severity, and the best course of treatment, suggested multiple other experts interviewed by Medscape Medical News. This difficult differential is not limited to ovarian cancer either, they noted. Many people with all types of cancer experience fatigue, loss of appetite, or cognitive impairment that could be from the malignancy, the cancer treatment, comorbid depression, or all three.

The Diagnostic Overlap Dilemma
“Because a number of symptoms of depression, such as loss of energy, loss of appetite, or difficulty concentrating are also symptoms of cancer or cancer treatment, it can be difficult, even for health or mental health providers, to separate physical symptoms related to cancer from those caused by comorbid depression in individuals being treated for cancer,” said Lora M.A. Thompson, PhD, senior member and clinical psychologist in behavioral medicine, Moffitt Cancer Center and Research Institute, Tampa, Florida.

“It’s important to take a whole-person approach to care so that we can address both physical and emotional well-being in all cancer patients,” added Thompson, who is also director of the Integrative Medicine Service at Moffitt.

The prevalence of major depressive disorder (MDD) after a breast cancer diagnosis, for example, ranges from 5% to 20% in the literature, a study by Thompson and Margarita Bobonis Babilonia, MD, estimated. “To properly diagnose and treat MDD, healthcare providers must be able to recognize depressive symptoms and distinguish them from similar somatic symptoms that are associated with breast cancer and breast cancer treatment,” they wrote.

What also makes determining the cause of somatic symptoms in people with cancer difficult is that depression seems like it can worsen somatic symptoms associated with cancer, and vice versa.

That was what the authors of a study of 487 people with advanced cancer found. In their research, depression severity was independently correlated with somatic symptom burden across 24 symptoms.

Depression severity significantly correlated with the number of physical symptoms, the distress the symptoms cause, and the severity of symptoms regardless of cancer type, functional status, chemotherapy status, or survival time (all P <.001), the authors wrote. “These findings support the view that a synergistic relationship exists between depression and a broad array of physical symptoms in patients with advanced cancer.”

Their research also suggests that the relationship between cancer and depression is bidirectional.

A Better Screening Solution?
Standard screening tools for depression often check for somatic symptoms, but they were not designed for people with cancer. That could contribute to some of the confusion by elevating depression scores, said Telles, who is also a researcher and doctoral candidate at the University of Iowa.

“When people are endorsing symptoms for another reason, say cancer, it makes that number go up, even though they’re not actually severely depressed,” Telles said. “They’re dealing with the cancer burden.”

Screening questions include whether patients are tired, stressed, or having difficulty eating. Depression screening instruments add one point for each, Telles noted, “even though there are other reasons patients could be endorsing that.”

She questioned why screening instruments designed specifically for people with both cancer and depression are not more widespread. “They have different screeners for women who’ve just given birth because we understand asking about sleep, food, and stress is a stupid thing to ask a new parent.”

Development of a specific tool to address these concerns could be helpful, Telles said.

Discerning physical symptoms of cancer from depression is also challenging for oncologists because some patients don’t associate some symptoms with the cancer, said Mali Barbi, MD, MSc, a medical oncologist specializing in gynecologic and breast cancers at Northwell Health Cancer Institute in New Hyde Park, New York.

“The patient could come in and say, ‘You know, I can’t sleep, but it’s because I’m so stressed. I’m so anxious.’ It is very hard as a doctor to escape that narrative,” Barbi said.

“Many times with cancer patients, everyone around them will tell them you’re very anxious, you’re very stressed, you need to let go,” she added, noting that this scenario reinforces attributing as many symptoms as possible to stress.

Also, “as physicians, we would like to think this is stress rather than this is the cancer progressing, the treatment not working, or the treatment not being tolerated,” Barbi said.

What’s At Stake for Patients
Wrongly ascribing somatic symptoms to depression can leave some patients with unresolved effects related to cancer.

“My background is in clinical psychology, so I work with a lot of patients who are referred for depression treatment and assessment,” Telles said. “F or the majority of patients, it’s a fantastic thing that they’re referred. It really helps them a lot.”

“And for others, there is this sense of frustration because they don’t have mood changes; they have what we call somatic symptoms. And they’re not finding relief from those through therapy,” she said.

Resolution of physical symptoms as the cancer treatment works is another indication that they were driven by the malignancy itself, said Claire Hoppenot, MD, assistant professor of gynecologic oncology at Baylor College of Medicine in Houston.

Misattributing symptoms can also affect survival. In a 2023 study of 779 people with cancer, for example, 46% reported cancer-related pain and the remainder non-cancer related pain. The researchers adjusted for depression, sleep, and other factors, and found that cancer-related pain was linked to significantly worse survival (hazard ratio, 0.646; P =.012).

Another study, published in 2021, links depression in people with cancer to shorter survival. When researchers assessed 20,582 patients across five cancer types, they discovered that major depression was associated with worse survival across the board (pooled hazard ratio, 1.41, P <.001).

Helping Clinicians Tell the Difference
Thompson pointed out that a depression diagnosis requires that patients endorse one of two primary symptoms — depressed mood or loss of interest/pleasure in activities — as well as additional nonsomatic symptoms, Thompson said. “Assessing for the presence of the nonsomatic symptoms such as crying, feelings of hopelessness, worthlessness or guilt, and thoughts of suicide would support a diagnosis of depression.”

Professional resources are available to help guide oncologists. For example, the National Comprehensive Cancer Network has guidelines on distress management and the American Society of Clinical Oncology released recommendations for managing anxiety and depression among adult survivors of cancer.

Asking about a history of depression prior to cancer is another tip, Thompson said. In a retrospective cohort study of 235,404 patients, researchers found that depression was associated with a subsequent cancer diagnosis. The prevalence of depression can also vary by cancer type, according to a 2013 meta-analysis that found it ranged from 3% in patients with lung cancer to 31% in patients with cancer of the digestive tract. Prevalence of depression was highest during treatment at 14% when assessed by diagnostic interviews and at 27% when measured by self-report instruments.

“Ultimately mental health providers will use clinical judgment to make a diagnosis of depression and offer appropriate evidence-based treatment approaches,” Thompson added.

Referral Advice
Depression screening is generally done at check-in and relevant scores are flagged for the provider. Telles suggests that oncologists contextualize the depression screener scores because even a brief conversation can change the course of care.

Ask patients whether they attribute symptoms to cancer treatment or to their emotional state, she said.

Some questions Telles suggests that clinicians use are, “Do you think there’s something going on?” and “Are you having a hard time?”

Another way to start the conversation with a patient is to say, “I notice you’re endorsing a lot of these symptoms. Here’s why I’d like to refer you to our psychologist — are you open to that?”

“I think the takeaway should be when in doubt, refer,” Telles said. “Psychologists are equipped to have these conversations with patients; that’s our job. But it’s helpful to talk to the patient and contextualize why they’re getting a referral to open that conversation.”

Looking Ahead
Biomarkers could aid in the differential diagnosis in the future. A study suggests that checking for fatigue biomarkers can distinguish somatic symptoms linked to cancer vs those of depression. For example, the researchers found a cluster of inflammatory markers linked to fatigue that were high in TNF-alpha, interleukin (IL)-1 beta, IL-6, and C-reactive protein and were not associated with depression. This suggests a future where more precise approaches could distinguish biologically -driven fatigue from mood-related fatigue.

Telles and colleagues’ study was conducted in Iowa and was predominantly White. Because depression can manifest differently across groups, the study findings warrant replication across cancer types beyond ovarian cancer, in more diverse racial/ethnic populations, and in male patients, the researcher said.

Telles is also working on identifying long-term risk factors for depression, including a lack of social support among people diagnosed with cancer.

The experts interviewed for this feature emphasized that the goal is not to stop referring cancer patients for psychological care but to ensure that referrals are well-contextualized, that screeners are interpreted in light of disease burden, and that somatic symptoms get the oncologic workup they may deserve.