Depression and Anxiety in Cancer Patients

by C.H. Weaver M.D. Medical Editor 2/2023

Facing a diagnosis of cancer or cancer treatment can be very stressful and may result in depression for some patients. Depression is a persistent sadness that interferes with your ability to complete daily activities. Treatment for depression depends on each individual, but is generally comprised of medication for controlling symptoms and counseling to deal with the underlying thoughts or feelings that led to depression.

• What is depression?
• What causes depression?
• What are the symptoms of depression?
• How is depression treated?
• What else can I do?

What is depression?

Depression is a persistent sadness that interferes with your ability to complete daily activities. Depression is more than sadness about a cancer diagnosis or concern about the future. Depression can result in overwhelming feelings of hopelessness and an inability to feel pleasure or even to function. The causes of depression are uncertain but may involve a combination of genetic, psychological, and environmental factors.⁴

The National Institute of Mental Health recommends seeking an evaluation for depression if five or more of the following symptoms are present every day for at least two weeks and interfere with daily activities:⁵

• Persistent sad, anxious, or “empty” mood
• Feelings of hopelessness and pessimism
• Feelings of guilt, worthlessness, and helplessness
• Loss of interest or pleasure in hobbies and activities that were
  once enjoyed, including sex
• Decreased energy
• Fatigue and a sense of being “slowed down”
• Difficulty concentrating, remembering, and making decisions
• Insomnia, early-morning awakening, or oversleeping
• Appetite and/or weight changes
• Thoughts of death or suicide or suicide attempts
• Restlessness and irritability

What causes depression?

While the actual causes of depression in cancer patients are not known, there are a variety of factors that can increase your likelihood of becoming depressed. These may include:

• Physical condition Poorly controlled pain An advanced stage of cancer Increased physical impairment or pain
• History Personal history of depression or attempted suicide Family history of depression or suicide History of alcoholism or drug abuse
• Lack of family support
• Other life events that produce stress
• Pessimistic personality

Medications commonly prescribed for management of your cancer may have depression as a side effect, such as:

• Chemotherapy drugs
• Hormones
• Immunosuppressive agents
• Steroids

What are the symptoms of depression?

The symptoms of major depression include:

• Depressed mood for most of the day and on most days
• Loss of pleasure and interest in most activities
• Nervousness or sluggishness
• Poor concentration
• Feelings of worthlessness
• Tiredness
• Changes in eating and sleeping habits
• Constant thoughts of death or suicide
• Guilt
• Feeling dissatisfied

For cancer patients, the most common symptoms of depression are:

• Guilt
• Worthlessness
• Hopelessness
• Thoughts of suicide
• Loss of pleasure

If you exhibit these symptoms for at least 2 weeks, you may be diagnosed with depression. However, it is sometimes difficult to separate the symptoms of depression from the side effects of treatment or the symptoms of the cancer itself.

How is depression treated?

Depression is most often treated with a combination of counseling and anti-depressant drugs. Medication is often used to ease symptoms so that other therapy can continue.

Anti-depressant drugs: There are different kinds of drugs available for the treatment of depression. Most antidepressants take 3 to 6 weeks to begin working and may be associated with some side effects. Even after you feel better, your doctor may recommend that you continue to take the medication for 6-9 months.

Venlafaxine (Effexor^®) is the newest antidepressant approved by the U.S. Food and Drug Administration in March 2003. Effexor^® is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI). Serotonin and norepinephrine are neurotransmitters, or chemical messengers in the brain; low levels of serotonin and norepinephrine have been associated with depression. Clinical studies have indicated that Effexor^® is more effective than Prozac^® in treating depression.

Currently, the most common, and perhaps the most well-known antidepressant drugs are called selective serotonin reuptake inhibitors (SSRI), the predecessor of SSNRIs. SSRIs increase the level of serotonin. While the SSRIs have gained popularity because of their relative safety and low incidence of side effects, they do still cause some side effects. Many of these will be short-lived, but if they are persistent or disturbing, you should consult your doctor.

Examples of SSRI's

• Fluoxetine (Prozac^®)
• Sertraline (Zoloft^®)
• Paroxetine (Paxil^®)

Common Side Effects

• Agitation, Nervousness
• Decreased sex drive
• Nausea
• Insomnia
• Headache

Another type of antidepressant drug called tricyclic antidepressants (TCAs) are often prescribed in severe cases of depression or when SSRI medications don’t work.

Examples of TCA's

• Amitriptyline (Elavil^®, Endep^®, Venatrip^®)
• Imipramine (Tofranil^®)
• Nortriptyline (Aventyl^®, Pamelor^®)

Common Side Effects

• Increased heart rate
• Blurred vision
• Drowsiness
• Sexual problems
• Dizziness
• Bladder problems
• Dry mouth

A third type of antidepressant drug is called a monoamine oxidase inhibitor (MAOI). Since the introduction of SSRIs, MAOIs are not used very often. However, your doctor may prescribe them if you are elderly because their side effects are relatively mild. You should carefully follow the prescribing instructions for MAOIs because they are associated with interactions and cannot be taken with many other drugs. You should wait several weeks before switching from SSRIs to MAOIs because of the risk of “serotonin syndrome.” This is too much serotonin in your body and can be a life-threatening condition.

Counseling: Psychotherapy, also known as “talk therapy”, can be an effective treatment for depression. There are several approaches to psychotherapy that have been used to relieve symptoms of depression. All of these involve working with a trained therapist to identify the thoughts or behaviors that are contributing to your depression and figure out ways to solve these problems and cope with depression. In general, psychotherapy takes weeks to months to complete.

Depression and Cancer Commonly Occurs. Its Treatable and is Often Neglected

Though an estimated 25 percent of cancer patients experience depression at some point during their illness—and despite the fact that untreated depression can affect quality of life, cancer treatment decisions, and possibly survival—depression often goes untreated.^1,2,3

Why are so few cancer patients receiving care for depression? The under recognition and the under treatment of depression in cancer patients may result from several factors, including patients’ reluctance to report depression, physician uncertainty about how best to manage it, and the belief that depression is a normal part of having cancer.

Although estimates of the frequency of depression in cancer patients vary widely, there is agreement that depression occurs more commonly in cancer patients than in the general population. Cancer patients also appear to be at greater risk for depression than patients with other serious illnesses such as arthritis, diabetes, heart disease, or chronic lung disease.⁶

For Laura, a breast cancer survivor from Upstate New York, depression followed a diagnosis of ductal carcinoma in situ (DCIS) at age 48. Although her prognosis was excellent, hearing the words “you have cancer” put her into a deep depression that she’d never before experienced. She cried every morning, pulled herself together enough to go to work, and then started crying again once she left her job. “Sometimes I wasn’t sure how I was going to be able to drive myself home,” she says. The weekends were even worse. She lost weight and talked with almost no one. “It was unlike anything I have ever felt before, and I pray I never go that way again,” she says. “It was such a lonely, lonely time for me.”

Tamara, 31, of Southern California, had what she describes as “a total breakdown” after a roughly yearlong workup for breast cysts. She describes the series of mammograms, ultrasounds, biopsies, and conflicting pathology reports as “overwhelming.” “It was a roller coaster,” she says. “Each time you’re preparing yourself for the worst.” She was eventually diagnosed with atypical ductal hyperplasia, a type of benign breast disease that put her at increased risk of developing breast cancer. She was put on tamoxifen to reduce that risk, only to be taken off of it by another doctor two months later. She knows that she should have been relieved by the diagnosis of benign breast disease, but she wasn’t. Instead she was struck by the realization that Nothing is going to change. This is how life is. The uncertainty would continue, along with the heightened risk of cancer. The stress of the preceding year, the prospect of continuing stress, and the hormonal fluctuations that came with starting and stopping tamoxifen—all threw her into a spiral. “I wanted out,” she says.

The Challenge of Identifying Depression in Cancer Patients

Given that depression in cancer patients is both common and treatable, why is it so commonly missed? The answer is likely to involve a combination of factors related to the patient, the physician, and the nature of cancer itself.

Several of the characteristics of major depression—fatigue, poor sleep, change of appetite or weight loss—will sound familiar to many cancer patients. These symptoms may result from cancer itself or from cancer treatment. The overlap of symptoms between cancer and depression has led to discussions about how to disentangle the two. As one researcher noted, “Mood change is often difficult to evaluate when a patient is confronted by repeated threats to life, is receiving cancer treatments, is fatigued, or is experiencing pain.”⁷ There are some characteristics of depression, however, that are not generally accepted as a normal part of the cancer experience. These include feelings of worthlessness and hopelessness, loss of pleasure, and thoughts of suicide. These thoughts and feelings may be the most useful in identifying cancer patients with depression.⁸

Addressing the issue of depression and cancer is further complicated by the wide range of other symptoms experienced by cancer patients.⁹ Given the number of health issues that need to be addressed, it’s not surprising that depression sometimes slips through the cracks. Furthermore, it may be difficult to decide what the treatment focus should be: is depression the problem most in need of relief, or would the symptoms of depression resolve if other symptoms, such as pain, were better managed?¹⁰ Ideally, one wouldn’t need to pick and choose among symptoms in this way, but it illustrates the challenge that physicians and patients face when confronted with simultaneous symptoms.

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Depression may also go unrecognized because many patients fail to report it.¹¹ Patients may feel that there is a stigma associated with the diagnosis or that addressing depression is not a priority compared with the challenge of cancer treatment. Furthermore, they may worry about how they would be perceived and treated by their physician if they were to express a sense of hopelessness. And the depression itself may make it difficult for patients to seek help.

Physicians might be able to overcome many of these barriers through thoughtful discussions with patients, but many physicians face barriers of their own. In Laura’s case, “The doctors seemed rather dumbfounded that I was so depressed and would shrug their shoulders and say, ‘You shouldn’t be.’” Their response made Laura feel even worse, but she faced a common problem. Whereas virtually all oncologists feel competent at managing pain, far fewer feel comfortable managing depression.¹²

The lack of response from her doctors was a crushing blow to Laura, but her brother encouraged her to discuss her depression with her primary care provider. She mustered the strength to walk into his office and announce: “I want antidepressants.”

Who Is at Risk for Depression?

It’s not possible to predict who will develop depression, but some people appear to be at greater risk than others. Factors such as a history of depression, a history of alcohol or substance abuse, and a lack of social support are likely to increase the risk of depression in both the general population and among cancer patients.¹³ Interestingly, although women in general are much more likely to develop depression than men, results in cancer patients have been mixed. Some researchers have reported that female and male cancer patients have a similar likelihood of developing depression.¹⁴

The presence of symptoms such as pain is strongly and consistently linked with the probability of depression.¹⁵ What remains uncertain is whether the symptoms cause the depression or whether the depression increases the patient’s perception of symptom severity. The relationship could work both ways.

In addition, there may be certain events during cancer diagnosis, treatment, or survivorship that make an individual particularly vulnerable to depression or other types of distress. Events such as finding a suspicious symptom, undergoing a workup, learning of the diagnosis, and awaiting, changing, or finishing treatment—all may make a patient particularly vulnerable.¹⁶

Although some characteristics of the patient or the cancer may help identify patients at high-risk of depression, one researcher offers the reminder that “Cancer, exclusive of site and stage of illness, is associated with a high rate of depression.”⁷

Depression and Cancer Outcomes

In addition to affecting an individual’s ability to function and enjoy life, depression may influence cancer outcomes, most importantly survival.^17,18

The issue of whether and how depression might influence survival is still being debated, but there are several possible explanations for a link: depression could have a direct effect on survival by influencing the immune or neuroendocrine systems, it may worsen cancer prognosis by changing cancer screening or treatment behaviors, or it may simply be a marker for more-severe disease.¹⁹

A handful of studies have suggested that depression can indeed interfere with the receipt of optimal treatment. Studies of breast cancer patients have reported that depressed women are less likely than nondepressed women to receive treatment considered “definitive”¹⁷ and are less likely to accept chemotherapy.²⁰

The ongoing debate about the relationship between depression and cancer survival should not obscure what may be the most important point: people who are depressed have limited functioning and poor quality of life. The suffering caused by depression warrants treatment regardless of whether it improves cancer outcomes. If treatment of depression is eventually shown to improve cancer outcomes, this will provide additional motivation for patients and physicians to identify and treat this condition.

Treatment of Depression

Standard approaches to depression management in the general population include psychotherapy and antidepressant medications. Although information about the effectiveness of these treatments in cancer patients is limited, there is little to suggest that their effect is different in cancer patients than in the general population.

It may take time to find a depression treatment that works. A change in type or dose of treatment may be necessary if a first attempt at treatment does not work or causes unacceptable side effects. Fortunately, many of the newer antidepressant medications produce fewer side effects than the older antidepressants. These newer drugs include selective serotonin reuptake inhibitors (SSRIs), such as Prozac^® (fluoxetine), Zoloft^® (sertraline), Paxil^® (paroxetine), and Lexapro^® (escitalopram); medications that affect both serotonin and norepinephrine, such as Cymbalta® (duloxetine) and Effexor^® (venlafaxine); and other medications, such as Wellbutrin^® (bupropion).

Adequate duration of treatment is another important aspect of depression management. For patients taking antidepressant medications, for example, a minimum of four to nine months of use is recommended.⁴

If patients are considering complementary or alternative approaches to depression management, they should discuss these approaches with their doctor to ensure that they are safe and won’t interfere with their cancer treatment. Saint-John’s-wort, for example, has received publicity as an herbal remedy for depression but it may interfere with certain cancer drugs.²¹ Furthermore, the effectiveness of Saint-John’s-wort remains uncertain.

Although she did manage to directly request antidepressant medications from her primary care provider, Laura was initially reluctant to consider them. She felt so bad that she couldn’t imagine anything making her feel better, and she was also concerned about side effects. Her doctor picked a medication that he thought would minimize side effects and take effect quickly. Within a week or two, Laura started feeling better. Though she still has traces of depression, Laura says that she is now able to do things that she couldn’t imagine doing when she was at her lowest.

Tamara and her husband decided that her condition was serious enough to warrant hospitalization. She spent 48 hours in the hospital, changed to a new antidepressant medication, and did outpatient therapy. She is feeling better and is finally able to find joy in the fact that she is currently cancer-free.

Depression at the End of Life

"That people are depressed because of their impending death should warrant, rather than preclude, aggressive treatment."

Ezekiel J. Emanuel, in his editorial “Depression, Euthanasia, and Improving End-of-life Care”

Depression at the end of life may pose the greatest challenge of all. The belief that depression is inevitable may be accentuated in the case of a dying patient. Patients with a short life expectancy also have a limited amount of time for treatment to take effect. Nevertheless, even among patients nearing the end of their lives, depression does not have to be accepted. Patients at this stage of life may have surrendered hope for recovery, but they may still retain hope for bringing closure to their lives, spending time with family, and having a painless death. Identifying and treating depression may help patients recognize and fulfill their hopes for this stage of their lives.

One of the most troubling aspects of depression at the end of life is that it is linked with an increased desire for a hastened death and requests for euthanasia. In response, a researcher at the National Institutes of Health has recommended making depression “a sixth vital sign.” Dramatic strides have been made in recent years in the recognition and the management of cancer pain, and similar progress in the area of depression is overdue.^22,23,24

Treatment of depression will have to be tailored to the needs of the dying patient. Many traditional antidepressants take weeks to work and dying patients may have only weeks to live. In the palliative care setting, psychostimulants such as methylphenidate have been shown to provide quick relief of depressive symptoms.^24,25

Seeking Help for Depression

The National Institute of Mental Health (NIMH) offers the following message for cancer patients with depression: “Remember, depression is a treatable disorder of the brain. Depression can be treated in addition to whatever other illnesses a person might have, including cancer. If you think you may be depressed or know someone who is, don’t lose hope. Seek help for depression.”²

If you think that you may be depressed, talk with your doctor, nurse, social worker, or spiritual adviser. And keep talking until you find the help you need. The burden of depression does not need to be added to the challenges of cancer diagnosis, treatment, and survival.

What do the studies show?

Major depression is an important complication of cancer that can result in additional impairment of quality of life.

A series of three articles published in the Lancet presented new research on depression in people with cancer and confirmed that depression is common, significantly undertreated, and can be improved once diagnosed and managed with an integrated treatment program, even in patients with major depression. The first article reported the results attained from screening over 21,000 patients with cancer in Scotland and the UK between 2008, and 2011.²⁶

The prevalence of major depression was 13.1% in lung cancer, 10.9% in gynecological cancer, 9.3% in breast cancer, and 7.0% in colon cancer. Major depression was more likely in patients who were younger and had worse social deprivation scores. Moreover 73% of patients with depression were not receiving potentially effective treatment.

A new multicomponent collaborative approach, known as Depression Care for People with Cancer (DCPC), was evaluated in 2 clinical trials: the SMaRT-2 study, reported in the Lancet, and the SMaRT-3 study, reported in the Lancet Oncology.(27,28) The integrated collaborative care model that was tested in these trials utilized a team of specially trained nurses, primary care doctors, and psychiatrists and demonstrated that this strategy can greatly improve outcomes for depressed patients with cancer compared with “usual care.” The SMaRT-2 study compared the effectiveness of an integrated treatment program for major depression in 500outpatients with cancer to usual care by a primary care physician. Overall, 62% of participants receiving the integrated treatment program for depression responded to treatment compared to only 17% of those in the usual care group.

Participants receiving the integrated care program also reported less depression, anxiety, pain, and fatigue. They also reported better functioning, health, quality of life, and perceived quality of depression care. The SMaRT-3 study evaluated an integrated depression treatment program in lung cancer patients with major depression. The results from this study indicated that even major depression can be treated effectively in cancer patients with a poor prognosis. Depression in cancer patients is under diagnosed and under treated. The results of these recent studies reflect the prevalence of depression among patients and demonstrates that the DCPC approach used in the SMaRT studies, combined with systematic screening, is one model of how to deliver better care for patients with cancer.

Many cancer centers in the United States have developed similar programs to the DCPC approach in the SMaRT studies for the diagnosis and management of depression in patients with cancer. In the past, many comprehensive cancer centers have provided an integrated approach to psychological support for their cancer patients, and they are all now required to offer these services to their patients. Find out if integrated approaches are available at your treatment center.

Virtual Support Groups: Anytime, Anywhere

Cancer patients count social and emotional support among the biggest benefits of social media. Virtual online support groups like CancerConnect offer patients, caregivers, friends, and family peer-to-peer support in a private, moderated and anonymous community accessible anytime, anywhere. “People with cancer and their caregivers need ongoing access to support—not just during a brief office visit with their physician, but when they go home and do research. They need help during sleepless nights as well as busy days,” explains Charles Weaver, MD, a medical oncologist and CEO of OMNI Health Media, the developer of CancerConnect.

Telecare Management May Improve Pain and Depression for Cancer Patients

A centralized, telephone-based system for symptom management appears to significantly reduce pain and depression among cancer patients who receive care in rural or geographically dispersed urban settings, according to the results of a study published in the Journal of the American Medical Association.

The Indiana Cancer Pain and Depression (INCPAD) trial evaluated a collaborative care approach to managing depression and pain in geographically dispersed oncology practices. The study included 405 patients from 16 oncology practices. Each patient participated in a depression and pain questionnaire. Two-hundred two patients were then randomly assigned to receive the intervention, while the remaining 203 were assigned to usual care. The intervention group received centralized telecare management by a nurse-physician specialist team combined with automated home-based symptom monitoring by interactive voice recording or Internet.

Patients in the intervention group experienced greater improvements in their pain compared with those who received usual care. Similarly, patients in the intervention group saw a decline in their depression compared with their counterparts. Patients in the intervention group experienced a 30% or greater reduction in pain and a 50% or greater reduction in depression.²⁹

The researchers concluded that a centralized telephone management system combined with automated symptom monitoring resulted in improved pain and depression outcomes in cancer patients receiving care in geographically dispersed areas.

What else can I do?

If you have suicidal thoughts, such as wanting to “end it all”, you need immediate assistance to ensure your safety. Tell someone—family, friends, or your doctor–immediately.

Make sure you are getting enough sleep and try to exercise daily. Being well rested will help you cope with difficult events and emotions. Exercise increases the release of natural chemicals in your body called endorphins, which promote a feeling of well-being. A daily exercise program can be as simple as 20-30 minutes of walking.

You may wish to try relaxation techniques to help you cope with your depression, such as:

• Meditation
• Yoga
• Deep breathing

References:

1. Not her real name.
2. Depression and Cancer fact sheet (NIH Publication Number: 02-5002). National Institute of Mental Health Web site. Available here Accessed August 24, 2006.
3. Jane Kenyon. “Having It Out with Melancholy” from Collected Poems. Saint Paul, MN: Graywolf Press. Reprinted by permission.
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