Diagnosis and Treatment of Depression in Cancer Patients

Drs. Pirl and Roth describe various problems that complicate efforts to accurately diagnose and appropriately treat depression in cancer patients. These include the subjective nature of symptoms, multiple possible diagnoses within the spectrum of mood disorders, multiple possible etiologies of somatic symptoms, lack of sensitive and specific diagnostic instruments, and attitudes of patients, caregivers, and clinicians toward the presence of depressive symptoms.

Another problem is the absence of controlled intervention studies. It follows that there also is a lack of consensus among those who work in the field. Although “obvious” cases of depression may be dealt with in a straightforward manner, the clinician often is faced with something of a dilemma: Which depressive presentations warrant treatment and how aggressive should that treatment be?

How to Identify Cancer Patients With Mood Disorders?

As noted by Pirl and Roth, the prevalence of depression in cancer patients is two to four times greater than that in the general population. In the definitive epidemiologic study of psychiatric illness in cancer, adjustment disorders and major depression accounted for the majority of all diagnoses.[1] How can patients with these psychiatric disorders be accurately identified?

The search for a valid, sensitive, and specific rating instrument for depression in cancer continues. Although several screening instruments are available, none is a substitute for a thorough diagnostic interview.

Pirl and Roth support the use of the Endicott substitutions for vegetative symptoms of depression in cancer patients. Although these criteria are potentially useful, it has not been established that their use improves diagnostic yield compared to standardized interviews and the use of criteria set forth in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM IV).[2]

Moreover, there may be some risk in ignoring or minimizing the importance of vegetative symptoms, which are valid diagnostic variables, despite the fact that they may also be sequelae of disease or treatment. Again, a careful history can help determine the etiology of vegetative symptoms.

When Are Medications Indicated?

Does an adjustment disorder that persists over some weeks represent an evolving depression? If so, when are medications indicated?

The somewhat contradictory observations of Pirl and Roth relative to the treatment of “reaction to bad news” and adjustment disorders highlight the difficulties encountered by clinicians. Whether patients faced with a cancer diagnosis go through defined, sequential stages of adjustment is debatable, as is the assertion that optimism about the future returns when treatment commences. For those in whom the treatment of depression will eventually be considered, this often is not the case.

If the issue of appropriateness or “normalcy” is irrelevant to the problem of diagnosis and treatment of a patient with depression, the same should apply to the patient experiencing distress when initially faced with the diagnosis of cancer. The clinical case scenario that Pirl and Roth present as a typical reaction to bad news—in which they assert that antidepressants would not benefit the patient—actually is an excellent description of an adjustment disorder, which, in some cases, they would treat with medications. Although it is generally held that supportive therapy is appropriate in this setting, it has not been established that antidepressants are of no benefit in the treatment of adjustment disorders, or that the risks of using them are any greater than in other instances.

As a practical point, many clinicians will medicate patients with adjustment disorders (and may neglect supportive therapy). They also will routinely encounter situations in which patients meet some, but not all, of the criteria for major depression (depression not otherwise specified, or minor depression, using DSM-IV criteria).

Depression Related to Therapy

As noted, relatively few cancer therapies have been directly associated with depressive syndromes. With some exceptions, vincristine, vinblastine, and asparaginase (Elspar) are not problematic in day-to-day practice. The neurotoxicity of the vinca alkaloids usually is peripheral, whereas asparaginase causes altered sensorium as often as depression.

Increasing numbers of patients receiving tamoxifen (Nolvadex) report depressive syndromes, with prominent dysphoria, anhedonia, and fatigue.[3,4] As the use of hormonal therapy expands, this is likely to become a more important management problem.

Much more problematic at present is interferon-alfa (Intron A, Roferon-A), which is associated with cognitive dysfunction and depressive syndromes in up to 50% of patients. It is surprising how often clinicians fail to inform patients of the possibility of cognitive and mood changes associated with interferon-alfa therapy.

The practice at some centers to deny interferon-alfa treatment to patients with a history of depression is not supported by convincing data. In fact, it is possible to treat depressed patients with interferon-alfa and other biological response modifiers.

It is also important to remember that treatment of cancer does not occur in a vacuum. The ability of patients to tolerate the depressive side effects of cancer therapies (or the disease itself) may be influenced by the severity of stressors in other parts of their lives. For this reason, a truly biopsychosocial approach to the diagnosis and treatment of depression is appropriate. The National Comprehensive Cancer Network (NCCN), a consortium of 17 major cancer centers, is developing guidelines for assessment that take into account the multiple variables that influence the level of distress, including depression.[5]

No Gold Standard for Treatment

As is the case with depression in the general population, there is no gold-standard treatment for depression associated with cancer. In the day-to-day care of depressed cancer patients, some form of psychotherapy usually is appropriate. Pirl and Roth provide an excellent description of the problems cancer patients face that may be dealt with by supportive or other forms of psychotherapy.

With regard to pharmacotherapy, many available antidepressants can be used in cancer patients. The general practice of “matching” a medication’s side effect profile to the patient’s particular symptom complex is applicable. However, if an antidepressant is to be used, it should be prescribed in an appropriate manner.

The belief that depressed cancer patients tend to respond to antidepressants more quickly and to lower doses than do healthy depressed patients is widely held, again without convincing support. Acceptance of this viewpoint risks the prescription of subtherapeutic doses of antidepressants for inappropriately brief periods of time. This does the patient a disservice. It is possible, and sometimes necessary, to become quite aggressive with antidepressants and psychostimulants, which are surprisingly well tolerated at high doses.

Clinicians should keep in mind that increasing numbers of depressed patients treat themselves with alternative therapies (eg, St. John’s wort). They do not always volunteer this information, in part, because of fear of the physician’s disapproval. Yet, because of the risk of adverse reactions, all patients should be asked if they are using alternative treatments.

Risk of Suicide

It is quite common for cancer patients to entertain suicidal thoughts at some point in the course of the disease. Discussion of these thoughts often can lead to opportunities for intervention even in individuals who are not actively contemplating ending their lives.

Although it is essential to inquire about suicidal ideation in any patient being assessed for depression, and to explore any expressed ideation thoroughly, cancer patients—whether depressed or not—are not suicides waiting to happen. Depressed cancer patients do not commit suicide at rates higher than “healthy” depressed patients. The suicide rate in cancer patients is actually surprisingly low, about twice that of the general population.[6,7] In contrast, nonmedically ill patients with mood disorders, including depression, have a risk of suicide up to 20 times that of the general population.[8]

Low-Threshold Approach

How should clinicians proceed? Although depressive symptoms are common in cancer patients, they often won’t talk about them. Physicians (and allied health professionals) must ask about these symptoms.

Intervention is a matter of clinical judgment. Depressive syndromes warrant treatment under the following circumstances: when symptoms significantly diminish quality of life, interfere with family interaction or vocational function, or interfere with treatment.

A low threshold for intervention means that some patients may be treated unnecessarily. A high threshold (using diagnostic criteria) means that some patients who would benefit from assistance may be missed. Until more accurate assessment tools and effective therapies are developed, appropriate treatment using the low-threshold approach is likely to be of most benefit to the most patients.

References:

1. Derogatis LR, Morrow GR, Fetting J, et al: The prevalence of psychiatric disorders among cancer patients. JAMA 249:751-757, 1983.

2. Kathol RG, Mutgi A, Williams J, et al: Diagnosis of major depression in cancer patients according to four sets of criteria. Am J Psychiatry 147:1021-1024, 1990.

3. Shariff S, Cummings CE, Lees A, et al: Mood disorder in women with early breast cancer taking tamoxifen, an estradiol receptor antagonist: An expected or unexpected effect? Ann NY Acad Sci 761:365-368, 1995.

4. Cathcart CK, Jones SE, Pumroy CS, et al: Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 27:277-281, 1993.

5. Holland J: NCCN practice guidelines for the management of psychosocial distress. Oncology 13(5A):113-147, 1999.

6. Albeck P, Bolund C: Suicide and suicide attempts in cancer patients. Psychol Med 21:979-984, 1991.

7. Breitbart W, Krivo S: Suicide, in Holland JC (ed): Psycho-oncology, pp 541-547. New York, Oxford University Press, 1998.

8. Angst J, Angst F, Stassen HH: Suicide risk in patients with major depressive disorder. J Clin Psychiatry 60(suppl 2):57-62, 1999.