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Major depression is common among patients with advanced cancer, and data support the efficacy of pharmaceutical intervention in this cohort. However, many more patients experience depressed mood, fatigue, and anxiety at levels that do not meet diagnostic criteria for major depression, and the efficacy of antidepressants in this group is unknown. In a new randomized trial, researchers evaluated whether pharmacologic intervention with a selective serotonin reuptake inhibitor (SSRI) improved health-related outcomes and lengthened survival in patients with advanced cancer and complaints of depressed mood, fatigue, or anxiety.
Eligible patients could be receiving palliative therapy and had metastatic cancer, life expectancy of at least 3 months, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate renal and hepatic function. Patients with major depression were excluded. At baseline, all 189 participants scored 4 or higher (scale range, 0–10) for depression, fatigue, low energy, or anxiety on the Patient Disease and Treatment Assessment Form (Pt DATA Form). Patients were randomized to daily oral sertraline (50 mg) or placebo; no dose adjustments were allowed. Any patient who developed major depression during the study was withdrawn. Patients completed the following surveys at 4, 8, 12, 16, 26, 39, and 52 weeks: Center for Epidemiologic Studies Depression scale (CES-D), Functional Assessment of Cancer General and Fatigue Scales (FACT-G and -F), Hospital Anxiety and Depression Scale (HADS), Somatic and Psychological Health Report (SPHERE), Utility-Based Questionnaire—Cancer (UBQ-C), Pt DATA Form, and Spitzer’s Quality of Life Index (SQLI). At baseline, 25% of patients had clinical depression, 8% had clinical anxiety (based on HADS), and 63% had moderate or worse fatigue (based on FACT-G). The primary outcome measure was clinical depression, as measured by CES-D.
Recruitment to this study was suspended after safety monitoring identified a potential adverse effect of sertraline therapy on survival. Patients on sertraline were contacted, informed of this result, and given the option to stop therapy. After a median follow-up of 19 months, no difference between sertraline and placebo was found in self-reported depression, anxiety, fatigue, or global quality of life. A predetermined minimally important benefit of 10 points on a 100-point combined symptom scale was statistically excluded. No difference in overall survival was noted in the final analysis. The authors concluded that treatment with SSRIs should be reserved for those patients with proven indications.
Stockler MR et al. Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: A placebo-controlled double-blind randomised trial. Lancet Oncol 2007 Jun 4; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S1470-2045(07)70148-1)
Comment
Many cancer patients experience symptoms of depression without meeting criteria for major depression. How do we treat such patients? Because of the relatively low toxicity of newer antidepressants, we have a tendency to initiate pharmacologic therapy without clearly distinguishing major depression from depressive symptoms. But do patients with depressive symptoms respond to antidepressants? A secondary question is whether other symptoms that are common in advanced cancer patients, such as fatigue and anxiety, will be alleviated by antidepressants. The results of this study suggest that antidepressants are not effective in patients with depressive symptoms, anxiety, or fatigue. Several concerns about this study must be noted. First, the dose of sertraline was low, and dose escalations were not allowed (however, 80% of serotonin reuptake is inhibited at doses of 50 mg daily). Second, although the primary outcome measure in this trial was depressive symptoms, only 65 of 189 patients who were enrolled in the study had moderate-to-severe depressive symptoms at the time of enrollment. Third, this population had advanced disease — whether results would be different in patients who were treated at an earlier point in their disease course is unknown. Nonetheless, I must agree with the authors’ conclusion that, at this time, SSRI therapy should be used only for patients with proven indications.