Whether to initiate therapy for depression depends on the probability that the patient will recover spontaneously in the next 2 to 4 weeks, the degree of functional impairment, and the severity and duration of the depressive symptoms.[1] Studies have shown that treatment of major depression is optimized by a combination of pharmacotherapy and psychotherapy. Thus, even if a primary care physician or oncologist undertakes the treatment of depressive symptoms pharmacologically, a referral for psychotherapy or supportive counseling should be considered.

Individuals should be referred for a psychiatric consultation for the following reasons:

• A primary care physician or oncologist does not feel competent treating the patient for depression because of specific clinical features in the presentation (i.e., if prominent suicidal tendencies are present).
• The depressive symptoms treated by the primary physician are resistant to pharmacologic interventions after 2 to 4 weeks of intervention.
• The depressive symptoms are worsening rather than improving.
• Initiating treatment with antidepressant drugs, titrating drug doses, or continuing treatment is interrupted or made problematic by adverse effects attributable to the medication.
• The depressive symptoms are interfering with the patient's ability to be cooperative with medical treatment.[2,3,4]

Pharmacologic Intervention

Overview

There is a paucity of randomized, placebo-controlled trials assessing the risks and benefits of antidepressants in patients with cancer and depression or depressive symptoms. Furthermore, these studies are limited by methodological challenges and a lack of broad representation of children, adolescents, older adults, and minority groups.[5] In certain cases of depression in patients with cancer, antidepressant therapy may be indicated. A survey of prescribing patterns in outpatient oncology settings over a 2-year period found that antidepressants were prescribed for about 14% of patients.[6] In a systematic review of newer pharmacotherapies for depression in adults, the response rate for treatment of depression with antidepressants was found to be approximately 54%.[7] The efficacy of the newer pharmacotherapies is similar to that of older antidepressants for general medical patients, including older adults and those with coexisting medical or psychiatric illness.[7] The dropout rates due to adverse effects are approximately 11% for newer antidepressants and 16% for older antidepressants.[7] Because of the relative paucity of data regarding antidepressant use in oncology settings, there is considerable variability in practice patterns related to prescribing antidepressants in cancer patients. Although studies generally indicate that about 25% of all cancer patients are depressed, one study found that only 16% of cancer patients were receiving antidepressant medication.[8]

Antidepressant Studies

• In adults, a double-blind placebo-controlled trial comparing fluoxetine with desipramine in treating depressive symptoms in 40 women with cancer found both medications to be effective and well tolerated. There were greater improvements on several quality-of-life measures in patients who received fluoxetine.[9]
• One study compared paroxetine with amitriptyline in the management of depression in women with breast cancer. Both treatments were equally effective. Paroxetine was associated with significantly fewer anticholinergic adverse effects than amitriptyline.[10]
• In a randomized controlled trial comparing fluoxetine with a placebo, patients receiving fluoxetine were found to have improved quality of life and decreased depressive symptoms.[11] Using a symptom-based approach (similar to the management of other cancer-related symptoms such as pain or nausea), this study assessed for depression by use of a 2-item screening procedure focused on presence of anhedonia (little interest or pleasure in doing things) and depressed or hopeless mood. Most of the sample consisted of patients with mild-to-moderate levels of depressive symptoms regardless of whether they met the diagnostic criteria for depression. Generalization was enhanced by inclusion of a sample of mixed cancer types (e.g., breast, thoracic, genitourinary, gastrointestinal) from a predominantly community cancer care setting, an equal male/female ratio, and a relatively large sample size (n = 163). A subgroup of patients identified as having higher levels of depressive symptoms was most likely to benefit from the treatment.