Recognizing Depression in Patients with Cancer

Caring for the “whole person” across the continuum of disease remains a top priority for clinicians. Strides in basic and translational research have opened new therapeutic pathways that provide better targeted and effective treatments with fewer side effects. New ancillary and supportive therapies have transformed and improved the experiences of patients undergoing anticancer treatments. Also, with increasing acceptance of multidisciplinary teams, we have the opportunity to make timely referrals to colleagues who provide supportive and palliative care and targeted interventions to treat pain and disabling symptoms. If our goal is to recognize the full impact of cancer on the lives of patients and their families, it is important to address the emotional and psychological toll of diagnosis and treatment. Recognizing depressive symptoms and clinical depression is an important step toward optimizing the quality of life for patients with cancer.

Data summarized in an excellent review by Pirl published in 2004 show that up to one in five Americans will experience depressive symptoms over the course of their lifetime and that approximately 10%–25% of cancer patients meet criteria for clinical depression.^{[1] and [2]} As our ability to treat depression has improved over the years, thanks in great part to advances in pharmacology and behavioral therapies, it is now critically important to recognize and treat this debilitating disease in individuals with cancer.³ Evidence exists that untreated depression is associated with a worse overall survival for some cancer patients and, paradoxically, that up to half of patients with cancer and concurrent depression are undertreated or receive no treatment.^{[4], [5] and [6]} Medical oncologists receive little or no formal training in psycho-oncology yet are often faced with patients who exhibit changes in mood and become progressively disabled by psychiatric symptoms. Methodical assessment and frequent inquiry may identify patients with cancer and depression.

Peeling Back the Onion: Sorting through Symptoms to Reach a Diagnosis

A diagnosis of cancer often precipitates intense emotions such as fear, sadness, and sometimes anger.² Individuals who may never have given much thought to their own death are confronted with the very real possibility of a shortened life and future suffering. Roles and relationships shift, careers are interrupted, and daily routines may be sacrificed to make room for cancer treatment. Add to this the financial worries that often accompany a serious illness and it is not surprising that patients may require some level of professional guidance or intervention in order to cope with the crisis. As a quick rule of thumb, it takes about 3–4 weeks after diagnosis to adjust, and during that period it is quite normal for patients to experience intense feelings.⁷ Weissman and Worden, among the first psychiatrists to study distress in cancer patients, described an acute syndrome of distress over existential plight with the diagnosis and with a recurrence that lasts about 100 days.⁸ Most individuals, given time and adequate support, will find the inner resources to cope with distressing symptoms and find a new normal. Not all do however, and it is important for oncologists to inquire at regular intervals about how the patient is feeling and coping with illness. A recent study by Lo et al⁹ found that predictors of depressive symptoms in patients with solid tumors included younger age, antidepressant use at baseline, lower self-esteem and spiritual well-being, greater attachment anxiety, hopelessness, the physical burden of symptoms, and proximity to death.

To facilitate screening for emotional distress in the context of a diagnosis of cancer, the National Comprehensive Cancer Network (NCCN) established guidelines that provide a reproducible algorithm for triaging patients with a suspected depression to mental health professionals.¹⁰ These guidelines were updated in 2010 and are widely available.¹¹ The consensus definition of distress in cancer is “a multifactorial, unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms and its treatment. Distress extends along a continuum, ranging from common feelings of vulnerability, sadness, and fears to problems that can become disabling, such as depression, anxiety, panic, social isolation, and existential and spiritual crisis.”¹⁰ By framing distress as a very broad concept, the guidelines separate the broad gamut of normal emotions from the distinct psychiatric syndromes of anxiety and depression which require specialized professional interventions.¹²

Distress may be a normal response to a threat or crisis, but depressive symptoms should alert the clinician that something more serious is going on. The appearance of persistent symptoms of dysphoria, hopelessness, helplessness, loss of self-esteem, feelings of worthlessness, and suicidal ideation indicates a psychiatric illness.¹³ The DSM-IV defines a major depressive episode as experiencing either dysphoria or anhedonia in addition to at least five somatic symptoms for at least 2 weeks.¹⁴ These somatic symptoms may well overlap with those experienced by patients as a direct result of their cancer or its treatment. Among these are changes in appetite, weight, or sleep; fatigue; loss of energy; and a diminished ability to think or concentrate. The challenge for clinicians is to tease apart the physiologic consequences of disease and side effects of medications from those due to profound and disabling psychiatric syndromes.

Many symptoms caused by cancer itself can be confused with neurovegetative symptoms of depression. Pain is known to modulate the reporting of symptoms; fatigue and weight changes are often secondary to cancer treatment or the illness itself. Patients often feel fatigued due to the heightened metabolic state present when there is a high burden of disease, and cytokines elevated in malignancy have been shown to cause fatigue and appetite suppression. There is a growing literature regarding the development of aberrant sleep patterns in patients with cancer, which can be mistaken for depressive daytime somnolence or insomnia.^{[15], [16], [17] and [18]} Some cancers themselves are associated with a higher risk of depressive symptoms, including pancreatic cancer and cancers of the head and neck.^{[19], [20] and [21]} Chemotherapy can also induce fatigue, insomnia, and anhedonia, as can the steroids often used concomitantly with chemotherapeutic or biologic agents. Interferon-alpha, used to treat melanoma and renal cell cancer, has been associated with depression in 3%–40% of patients; and there is a 5% rate of suicidal thoughts.²²

Cancer patients exhibit a range of coping styles and varying degrees of emotional resiliency. If a patient is able to process his or her emotional responses to the physical threat of a diagnosis and becomes mobilized in such a way that he or she obtains useful information and is able to prioritize concerns, obtain social support, and move toward a coherent treatment plan, one can easily assume that he or she is coping well.²³ On the other hand, if the patient appears unable to make a decision about treatment, avoids addressing or discussing important issues, and retreats from family, friends, and/or the medical team, one can infer that he or she is having trouble coping and could benefit from a referral to a mental health professional for evaluation.²³ Known risk factors for poor coping and for developing depression include social isolation, use of few coping strategies, a history of recent losses or multiple obligations, inflexible coping strategies, the presence of pain, and socioeconomic pressures.^{[8] and [23]} In extreme cases, patients may resort to deferring decisions or simply denying the problem.

Keep in mind there may also be cultural or personal barriers that interfere with a timely and accurate diagnosis of depression.¹² Many families believe strongly in the “power of positive thinking” and need to feel that their family member is a “fighter.” This type of encouragement may at times be helpful for a patient, but it may not leave a safe opening for the expression of fear, pain, or depressed mood. If the matriarch or patriarch of the family has supported everyone else through the difficulties in their lives, she or he may not feel able to show weakness and seek help for depression. This can be a difficult patient to diagnose as the only clue to suffering may be easy to miss. In fact, if there are very few questions or complaints when there is clear physical suffering, one needs to worry that the patient is unable to express his or her deep concerns. The clinician who spots this situation early on may be able to lead the patient in the direction of expressing his or her feelings by suggesting that others in similar situations also experience stress or sadness. Finding a private time to talk, away from family members, may also provide a more comfortable environment for a candid conversation.

If we think of the disease trajectory as a marathon, then we can learn to recognize certain landmarks along the course and remember that these pose enormous challenges to patients. In addition to receiving the initial diagnosis, the period of active treatment, the conclusion of active treatment, and the time of disease recurrence pose specific challenges and precipitate intense emotions. Disease recurrence is a time of great anxiety when there is a need to plan for future treatment and an upheaval of the timeline a patient may have made.²⁴

Should the Oncologist Offer Treatment for Depression?

Oncologists assume an important role in the medical care of their patients and often initiate or modify treatments for other medical conditions. If a patient develops hypertension or diabetes during or as a direct consequence of treatment, most oncologists feel comfortable starting medication and may then comanage the patient with internists. Primary care physicians and oncologists are typically familiar with a few basic antidepressants, and many are willing to prescribe these for patients who meet the diagnostic criteria for depression, especially since it takes weeks to achieve adequate therapeutic levels for many of these drugs. Recognizing the presence of depression is thus a key diagnostic intervention.

Several efforts have been made to develop self-report screening inventories that can improve the accuracy and efficiency of detection of depressive symptoms and are brief enough to administer in the setting of an office visit. Some tools have been validated and correlate well with more detailed inventories, although the gold standard remains the detailed psychiatric interview.²⁵ A single-item interview screening proposed by Chochinov et al²⁵ years ago performs as well as or better than longer instruments and is remarkably simple to remember. Asking patients “Are you depressed?” in a brief screening interview correctly identified the eventual diagnostic outcome of every patient in initial studies and has been adopted broadly by oncologists and palliative care clinicians caring for patients who are terminally ill.

We support immediate referral to a psychiatrist for any patient who exhibits symptoms of depression, and there is universal agreement that any person who may be suicidal should be referred immediately for urgent psychiatric evaluation. In practice, however, there are two main barriers to successful referrals for those who may be considered to be “managing” and not considered at risk for suicide: Patients are sometimes resistant to or reluctant to accept a recommendation for referral, and the shortage of mental health professionals trained in psycho-oncology limits quick access. It is, therefore, not surprising that cancer clinicians often initiate pharmacologic therapy for depression and provide emotional support to patients and families. Kadan-Lottick and colleagues⁵ reported that although 90% of patients agreed that they were willing to receive treatment for emotional distress associated with their cancer diagnosis, only 28% accessed treatment. Approximately 55% of the patients diagnosed in that study with major psychiatric disorders did not access treatment. It has been our experience that oncologists are often willing to initiate pharmacologic therapy while the patient is waiting for an appointment with a specialist.

The most frequently prescribed antidepressant medications are the selective serotonin reuptake inhibitors (SSRIs). Frequently, the choice of antidepressant is based on the side-effect profile of a particular medication as there are many effective options, none of which appears to be significantly more efficacious than the others.⁷ Antidepressants considered to be sedating may not be the preferred option for patients who have significant neurovegetative symptoms including fatigue and low energy. Conversely, antidepressants that cause anorexia and insomnia are poor options for patients experiencing sleepless nights and continued weight loss. Options for more activating antidepressants include sertraline, escitalopram, bupropion, and venlafaxine, while more sedating antidepressant medications include paroxetine and mirtazapine.⁷ Methylphenidate, a drug frequently used to treat attention-deficit/hyperactivity disorder, has been very effective in patients with low energy and anorexia.^{[26] and [27]} Starting at a low dose in the morning, especially in the elderly, helps to minimize tachycardia and sleeplessness, which can be unwanted side effects of this medication. Lastly, a key point when choosing a medication is the potential for drug–drug interactions. Multiple antidepressants, including paroxetine, fluoxetine, fluvoxamine, and bupropion, interact with the cytochrome P-450 2D6 system, making them more likely to interact with medications commonly used in oncology.²⁸ One example of this potential for interaction occurs with tamoxifen, which is metabolized into its active form, endoxifen, by the cytochrome P-450 2D6 system. It may not be available in adequate concentrations in the setting of antidepressant medications like paroxetine, an inhibitor of cytochrome P-450 2D6. Whether this ultimately influences the efficacy of anticancer treatment is still under investigation.

While psychotherapy is outside the scope of most practicing oncologists, it may be helpful to provide patients with some guidance about the range of available therapies. Individuals may express a clear preference for nonpharmacologic treatments, so it is important for cancer clinicians to familiarize themselves with a few such options. These include cognitive behavioral therapy (CBT), intensive psychotherapy, and group therapy. These interventions can aid patients in reducing anxiety and in strengthening their personal coping mechanisms. Studies to rigorously evaluate the efficacy of these interventions have been challenging to complete because of the lack of a “gold standard” definition of depression in cancer, no consensus on an appropriate length of treatment, no clear way to monitor compliance with a given therapy, and varied definitions of appropriate end points.¹² Despite the challenges, several meta-analyses have been compiled to sort through the data. The more commonly referenced meta-analyses have included thousands of patients undergoing nonpharmacologic interventions ranging from individual psychotherapy to group therapy as far back as 1954.^{[29], [30], [31], [32], [33] and [34]} None of the interventions indicate that any particular therapy is more clearly beneficial than another.

CBT has received recent attention and appears to be a good option for many cancer patients with depression. A review by Williams and Dale in the British Journal of Cancer in 2006³³ outlines 10 studies focusing on the use of CBT in cancer patients with mixed results. Of these, only two found CBT to be ineffective, whereas the rest demonstrated some benefit in reduction of depressive symptoms and improvement in quality of life for patients with a wide assortment of primary malignancies. Most found early improvement in symptoms but not necessarily long-term persistence of the initial positive effects. Group therapy has also been thoroughly studied in depression in cancer patients since Spiegel's landmark study in the late 1980s and has been shown to decrease anxiety, depression, and pain and to increase effective coping.^{[34], [35], [36], [37], [38] and [39]} Many patients report positive experiences in support groups, but others express an intuitive fear that listening to other patients' concerns and negative thoughts will impair their own overall mood and outlook. Not all patients feel comfortable expressing their personal fears, doubts, and frustrations with a group of relative strangers. Any of these concerns is a sufficient reason to advise more personalized attention in a private therapy session with a specialist. Choosing between individual psychotherapy, group, and family therapy can be construed as another aspect of providing truly “personalized” cancer care.

A substantial number of patients worldwide turn to complementary and alternative therapies for the treatment of cancer and cancer-related symptoms.^{[40], [41] and [42]} Estimates of the prevalence of complementary and alternative therapy use vary widely due to differences in definitions and inaccuracies in self-reporting and patient selection. There are emerging data that up to 60%–80% of cancer patients avail themselves of some form of alternative therapy at some point in the trajectory of their disease.⁴² This number varies widely, likely because the definition of “complementary and alternative therapies” is so broad and can include prayer, use of herbal medications, acupuncture, and meditation. In one study of early-stage breast cancer patients, the use of alternative medicine was significantly associated with patients experiencing depressive symptoms, heightened fear of recurrence, greater physical symptoms, and poor sexual satisfaction.⁴² At 1 year, all patients, both those using complementary and alternative therapies and those using traditional methods of care, experienced an improvement in quality of life.

For patients who do not meet the criteria for clinical depression and have no interest in or access to support groups, it is worth remembering there are other interventions that can facilitate adjustment and diminish symptoms of anxiety. Expressive writing, music, or art therapy and other activity-based therapies may provide the necessary vehicles for self-expression.

Conclusion

Depression clearly affects patients with cancer, and establishing the depression diagnosis is the first step toward progress in treatment. Despite the challenges, diagnosis is possible by establishing that the symptoms of depression are negatively impacting patients' abilities to cope with their circumstances and maintain balance in their lives. It is critical not only to make the diagnosis of depression but also to strongly encourage patients to seek treatment, either through pharmacologic or nonpharmacologic means. While we make every effort to eradicate our patients' malignancies, we owe it to them to work just as diligently to improve their daily lives by treating associated depression.