Disclosures: Alfano, Andersen, Blackhall, Mitchell and Philip report no relevant disclosures. Balkrishnan reports a consultant role with Merck & Co.
August 25, 2020
12 min read

Depression, anxiety in cancer survivors: An underrecognized ‘emotional crash’

Disclosures: Alfano, Andersen, Blackhall, Mitchell and Philip report no relevant disclosures. Balkrishnan reports a consultant role with Merck & Co.
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The successful completion of active treatment is an important milestone for anyone who has lived with cancer. However, being cancer-free does not always bring the peace of mind patients might expect.

Along with the physical remnants of treatment, cancer survivors often continue to grapple with anxiety and depression. In some cases, these feelings may even intensify after treatment.

“We know from research that has been done on people transitioning to post-oncology treatment that they feel ‘dropped,’” Catherine Alfano, PhD, vice president of cancer care management and research at Northwell Health Cancer Institute, said in an interview with Healio. “They’ve had so much support during cancer treatment. They had their oncologist and oncology nurse and everyone who was looking out for them. They had friends and family rallying around them. That all pulls away when oncology treatment is done. They’re basically told, ‘OK, we’ve treated your cancer, now go live your life.’”

Alfano maintained that the logical way to manage anxiety and depression in cancer survivors is to recognize and address the problem during cancer treatment.

Catherine Alfano, PhD
Catherine Alfano

“We need to identify patients who are having clinically significant anxiety and depression during their oncology treatment and then help them access treatment, so it doesn’t continue into the post-cancer treatment phase,” she said.

Unfair expectations

Although it may not be possible to precisely quantify their prevalence, anxiety and depression appear to be common among cancer survivors, according to Errol J. Philip, PhD, director of Precision Health California.

Errol J. Philip, PhD
Errol J. Philip

“Studies suggest that more than 20% of survivors have symptoms that should be addressed by a health professional, and many more possess subclinical symptoms or anxiety,” Philip told Healio. “Whereas such symptoms, in and of themselves, are associated with significant suffering for survivors, they can also interfere with the ability to engage in behaviors that we know can improve long-term disease outcomes.”

For example, Philip said, symptoms of depression and anxiety can jeopardize compliance with disease follow-up and surveillance, impair engagement in exercise and healthy diet planning, and interfere with a survivor’s ability to connect with family members and friends or seek professional help.

“The transition to survivorship can be a challenging period for patients, often characterized by fewer medical visits and less direct support from their medical team, as well as both their own and their families’ expectations that they should be celebrating or relieved and will now be ready to return to their precancer professional and personal roles,” Philip said. “These expectations can place pressure on survivors and sometimes exacerbate existing symptoms of depression and anxiety.”

Even clinicians may not fully understand the transition from treatment to survivorship from a patient’s perspective. According to Leslie Blackhall, MD, section head of palliative care at the University of Virginia, physicians tend to view successful treatment as a victory, having seen the alternative.

Leslie Blackhall, MD
Leslie Blackhall

“Oncologists — and doctors in general — know what can happen if somebody doesn’t get their cancer treated in time,” Blackhall said in an interview with Healio. “So, when we see a patient a month after treatment and they don’t have any sign of tumor, it’s awesome. However, the patient is much different than they were before they underwent treatment. We’re comparing them to what we know is the worst-case scenario, and they’re comparing themselves to what they used to be. What is considered recovery to us and what is considered recovery to them are very different.”

Gaps in care, screening

Although some studies have suggested that treating depression may improve cancer outcomes, the data are not consistent on this correlation. A 2018 study in Lancet Psychiatry showed that depression treatment had no significant impact on survival among participants in the SMaRT Oncology-2 and 3 trials (Mulick et al.).

“There is a paradox in that depression and other significant mental health complications are associated with worse cancer outcomes after a cancer diagnosis, but studies to date have struggled to demonstrate a survival benefit when depression is treated,” Alex J. Mitchell, MD, of University Hospitals of Leicester and University of Leicester, and author of a related editorial, said in an interview with Healio.

“One plausible explanation is that patients with depression, anxiety, dementia and schizophrenia receive lower quality cancer care after their diagnosis, as well as less frequent population screening for cancer before their diagnosis. In fact, these have both been confirmed in a large number of studies. However, why does a gap exist in medical care and medical screening in the first place?”

Mitchell said this gap might be attributable to low attendance when patients are called for procedures or screening. He emphasized that more effective means of reaching these patients are needed to ensure quality follow-up care and optimal cancer outcomes.

Mitchell added that the belief among some clinicians that people with mental health problems cannot be treated equally may contribute to the gap in care among these patients.

“For example, a negative attitude of general practitioners toward cancer screening in people with mental illness has been reported to be associated with a 20% increased likelihood of patients forgoing cancer screening procedures,” he said.

Mitchell said although depression interventions have not been found to convincingly change the survival course of patients with cancer, the sample size of studies to date has been too low and the treatments too brief to conclusively demonstrate this. He said the study by Mulick and colleagues showed a small effect (a 7% decrease in the hazard of death for each point on a depression score), but this was not statistically significant.

Additionally, cancer outcomes among depressed patients appear to vary based on cancer type and location, as well as patient characteristics and the type of depression treatment offered, Mitchell said.

“Shoval and colleagues recently found lower mortality after cancer [among patients with depression] but only in those with good vs. poor adherence to their medication,” Mitchell said. “Depression had a worse effect on mortality in male patients and no effect [among patients with melanoma]. In terms of well-being, depression treatment has a large influence on quality of life if it is commenced early, using evidence-based treatment that is acceptable to the patient.”

Mitchell said only 40% of patients with cancer who have depression accept offers of psychological help. Additionally, he said, some cancer centers continue to offer inappropriate treatment options.

“For example, very simple IAPT [Improving Access to Psychological Therapies]-based counseling, which is very popular in the U.K., does not appear to work effectively in patients with advanced cancer where a specialist psycho-oncology service is needed to match patient needs with an appropriate treatment option,” he said, referring to findings by Serfaty and colleagues published in The British Journal of Psychiatry.

Despite the overall lack of a significant association between depression and cancer outcomes, Mitchell said depression treatment may have long-term survival benefits for cancer survivors.

“Depression treatment might help long-term mortality after cancer, because more than half of [patients with cancer] outlive their cancer risk entirely,” Mitchell said. “Indeed, Ko and colleagues found that although depression itself negatively influenced cancer-related mortality in the first 5 years of survival, depression also had a large effect on noncancer causes of death beyond 5 years. Therefore, we perhaps need to think more long-term with [patients with cancer] and depression.”

Living with stigma

Although survivors of all types of cancer experience depression and anxiety, these conditions are particularly prevalent in certain cancer types.

“Historically, among all [patients with cancer, those with lung cancer] have had the highest rates of anxiety and depressive symptoms, with [patients with pancreatic cancer] occasionally ‘tying’ them in this respect,” Barbara L. Andersen, PhD, professor of psychology at The Ohio State University, said in an interview with Healio. “A variety of data suggest that [patients with lung cancer] are, indeed, the most psychologically impaired group of people with cancer.”

Barbara L. Andersen, PhD
Barbara L. Andersen

Andersen added although the base rate of suicide among patients with cancer is relatively low overall, those with lung cancer have been shown to have the highest rates of suicide. She discussed possible reasons for the historically high rates of depressive symptoms and anxiety among patients with lung cancer.

“It’s certainly always been attributed to the fact that the ‘common lore,’ often true, was that it was a fatal disease,” Anderson said. “For 70% of the people, it was a fatal disease that progressed very rapidly.”

Additionally, the association between lung cancer and nicotine use — which Andersen said is an instrumental factor in about 90% of cases — may lead these patients to feel responsible for their disease.

“There is some newer literature on lung cancer stigma that suggests a common perception that if the patient hadn’t smoked, they wouldn’t have gotten lung cancer,” Andersen said. “So, there is that factor; patients may feel responsible. However, it is also important to know that guilt is a depressive symptom.”

When viewed this way, Andersen said, it is not always clear whether the guilt is specific to a smoking habit or is part of a more generalized constellation of depressive symptoms.

“Just as a depressed person might feel hopeless and have a chronically low mood, low motivation, sleep or appetite problems, they might experience guilt as a symptom,” Andersen said. “They might feel guilty about how they interacted with their kids this morning or about all kinds of things in their lives. When they become depressed, they might experience guilt, and then the smoking habit might become the focus of that guilt.”

Inflammatory processes involved in lung cancer also may play a role in depression among these patients, Andersen said.

“Lung cancer is the product of a dysfunctional immune system, and that comes with inflammation. The process of inflammation and inflammatory cytokines exists for depression, as well. So, it may well be that concurrent inflammation is pushing the disease but may also drive emotions.”

This raises the question of whether maintaining an inflammatory state due to depression could possibly put a patient with lung cancer at risk for a worse outcome or cancer recurrence. Andersen said the short answer to this question is yes and discussed a randomized trial she conducted in 2008 among patients with breast cancer.

The trial assessed 227 women who underwent surgical treatment for regional breast cancer. Half of the women participated in a psychologist-led intervention, in which small groups discussed strategies to reduce stress, improve mood, change health behaviors and remain compliant with cancer treatment. The other half were placed in an assessment-only group.

Andersen and colleagues found that after 11 years of follow-up, women in the intervention group had a decreased risk for breast cancer recurrence (HR = 0.55; P = .034) and for breast cancer mortality (HR = 0.44; P = .016) than those in the assessment-only group.

“I could see the survival effect in [patients with breast cancer],” Andersen said. “I cannot imagine how huge the effect would be with [patients with lung cancer].”

Andersen discussed the fear of recurrence that often occurs among lung cancer survivors. However, she added that, as with guilt, fear of recurrence may be part of a more generalized anxiety disorder.

“If you have generalized anxiety, you become worried and fearful about all kinds of things,” Andersen said. “In all the worries of life, of course a cancer survivor might be worried about recurrence, but if it becomes debilitating, I think what you’re looking at is generalized anxiety disorder.”

Risk for opioid abuse

Even after active treatment, cancer survivors may require medication to prolong survival and prevent recurrence. For example, many breast cancer survivors continue to take hormone treatments, according to Rajesh Balkrishnan, PhD, professor of public health sciences at University of Virginia School of Medicine. These medications, although effective, may cause painful musculoskeletal adverse effects. In some cases, a short course of opioid medications may be prescribed for these symptoms.

Balkrishnan and colleagues conducted a study on the use of opioid medications among breast cancer survivors.

Rajesh Balkrishnan, PhD
Rajesh Balkrishnan

“In our study, we found that women who were depressed or anxious were less likely to taper off these medications, and more likely to continue to fill their opioid prescriptions,” Balkrishnan told Healio. “This was especially true of women who were living in rural areas of the United States.”

Balkrishnan said specific de-escalation guidelines need to be established to control the use of opioids. He also called for closer scrutiny of potentially irresponsible prescribing practices around these drugs.

“It’s surprising, but there are areas of this country, especially in rural Appalachia, where patients have to drive several miles to get to a primary care physician, but they have a ‘pain clinic’ within their town,” he said. “I think we need to closely monitor physicians who might be overprescribing these medications.”

A ‘policy wake-up call’

The best approach to treat depression or anxiety in a cancer survivor generally depends upon the patient’s needs and preferences. However, many clinicians agree that cognitive behavioral therapy (CBT), medication or a combination of the two can be effective.

“Counseling, most notably CBT, possesses a strong foundation and evidence base in the treatment of depression and anxiety,” Philip said. “The limited availability and affordability of individual counseling services has driven innovation in the field of supportive care, with the development of online or app-based interventions, self-guided books and group-based psychological care, all of which can be effective in addressing symptoms of depression or anxiety.”

Alfano said the American Psychosocial Oncology Society (APOS) has created a growing registry of mental health providers who specialize in oncology. She said these providers are trained to offer mental health care to individuals at any point along the cancer journey.

“Whether that’s during oncology treatment or any time after treatment, it doesn’t matter,” Alfano said. “This is a registry of providers who understand the mental health issues, whether that’s anxiety, depression or even cognition.”

The cost of CBT or other treatments is a significant obstacle to quality mental health care for cancer survivors. Alfano said the issue of cost is a much larger problem than the oncology community and the public might realize.

“So many of our patients have had trouble paying their bills for cancer care; the last thing they can afford to do is pay additionally for mental health,” Alfano said. “They got through cancer, but now they’re still suffering, because we aren’t able to affordably offer them the mental health care they need. It’s disgusting; it’s immoral.”

Alfano stressed the need for a “policy wake-up call” to improve insurance reimbursement for mental health services for cancer survivors. She also noted that enabling mental health professionals to provide telemedicine services across state lines could substantially improve access to care, particularly for patients in states where these providers are in short supply.

“Say there is a patient diagnosed in Montana. There are no mental health clinicians in Montana who can help them,” Alfano said. “Why can’t that clinician in California, via telemedicine, help treat that patient in Montana?”

Alfano discussed the unique opportunity presented by the COVID-19 pandemic, which has caused some states to lift restrictions on telehealth across state lines. She said rather than viewing this expansion of telehealth as a temporary emergency measure, clinicians should see it as the beginning of a permanent, positive change.

“We’re sitting at this critical place where, because of COVID, some of these restrictions, like allowing telehealth in mental health and allowing clinicians to practice across state lines, have been lifted,” Alfano said. “We need to keep that. Why would we want to return to the way things were, where we were limiting patient access? Why would we want to go backward?”

Alfano said for oncologists, primary care providers or other clinicians who follow cancer survivors, talking to these patients regularly about their mental health symptoms is the best way to keep these symptoms under control.

“The APOS and National Comprehensive Cancer Network guideline calls for doctors to routinely use an anxiety and depression questionnaire to ask patients about their anxiety and depression symptoms,” she said. “The goal is to pick it up so that you know it’s developing, and then make sure you’re giving the patient a referral that is feasible. If you refer a patient to a medication or a therapist that they can’t afford, you haven’t really helped them.”

Exercise is another effective intervention that almost any cancer survivor can access, Alfano said.

“One of the best ‘drugs,’ if you will, for fatigue, anxiety and depression is exercise,” she said. “So, I think of it as a three-pronged approach: medication, therapy and exercise.”

Blackhall said compassion and empathy for cancer survivors are essential. This means understanding that these survivors may continue to cope with symptoms like fatigue, depression, anxiety and more for years after treatment.

“I think the emotional crash that comes with the transition to survivorship can last longer when people have guilt about it,” she said. “People try to do everything they used to do, and when they can’t, they feel guilty. Then they feel guilty about feeling guilty. It’s not helpful.”

Blackhall said in some cases, depression and anxiety among cancer survivors can ultimately open doors to treatment and a better life than they had before.

“One of the things I find satisfying at my clinic is that there are people who have had depression or severe, generalized anxiety their whole lives and didn’t get treated for it until they got cancer. Then they came into contact with people who were willing to treat it,” Blackhall said. “It’s a life-transforming thing. I think these people may have had that tendency, and the stresses of cancer treatment tipped them over. Seeing them improve is incredibly rewarding.”


For more information:

Catherine Alfano, PhD, can be reached at calfano3@northwell.edu.

Barbara L. Andersen, PhD, can be reached at andersen.1@osu.edu.

Rajesh Balkrishnan, PhD, can be reached at rb9ap@virginia.edu.

Leslie Blackhall, MD, can be reached at lb9x@hscmail.mcc.virginia.edu.

Alex J. Mitchell, MD, MSc, MRCPsych, MBBS, can be reached at ajm80@leicester.ac.uk.

Errol J. Philip, PhD, can be reached at errol.philip@ucsf.edu.