SAN FRANCISCOTwo brief questions can help clinicians decide which cancer patients might benefit from treatment with antidepressant drugs.
Reporting on behalf of the Hoosier Oncology Group, Michael J. Fisch, MD, said the two questions are:
1. During the past month, have you been bothered by feeling down, depressed or hopeless?
2. During the past month, have you been bothered by having little interest or pleasure in doing things?
"Depression is not an inevitable consequence of living with cancer," Dr. Fisch stated. The symptoms described in the two questions "are responsive to treatment," he added, "but diagnosing and treating symptoms of depression do not represent the current standard of care in most oncology practices." Dr. Fisch is with the Department of Symptom Control/Palliative Care at the University of Texas M.D. Anderson Cancer Center in Houston
Quality of Life Improved
Dr. Fisch said that patients selected by their responses to those two questions and treated with fluoxetine(Drug information on fluoxetine) (Prozac) had significant improvement in depressive symptoms and in quality of life (QOL) measurements compared to similar patients randomized to placebo. The choices for responses and the point values assigned were: 0 = Not at all; 1 = A little; 2 = Somewhat; 3 = Quite a bit; and 4 = Very much. The total score was the sum of the answers to the two questions and could range from 0-8. Patients with a sum score of 2 or greater were eligible. Patients with a sum score of 4 or greater were in the subgroup that was most likely to benefit in terms of quality of life and improvement in depressive symptoms. Although a selective serotonin reuptake inhibitor (SSRI) was used in this study, Dr. Fisch said that there are few differences between antidepressants with regard to efficacy in treating depression in cancer patients. SSRI antidepressants are used more often than tricyclic antidepressants in cancer patients because they are well tolerated, nonlethal in overdoses, and there is no need to follow blood levels.
The Hoosier Oncology Group undertook this trial because there were no controlled data regarding the efficacy of simple screening for depressive symptoms and treatment of those symptoms with an antidepressant in cancer patients.
This double-masked, randomized, placebo-controlled study included 163 outpatients with an advanced solid tumor, some indication of distress, and an expected survival between 3 and 24 months. Patients with major depression, suicidal ideation, central nervous system metastasis, or elevated bilirubin were excluded.
Patients who gave at least some indication of distress on the screening questions and had no recent or concurrent exposure to antidepressants were randomized to receive either fluoxetine 20 mg daily (n = 83) or placebo (n = 80) for a total of 12 weeks. Patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0 or 1 vs ECOG 2 or 3).
Longitudinal assessments were performed every 3 to 6 weeks including quality of life, depression, and spiritual well being. The primary objective was to compare the change in quality of life of patients treated with fluoxetine vs placebo, as measured by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. Secondary endpoints included assessment of depression and spiritual well being.
Dr. Fisch reported that patients in the fluoxetine group had significant improvements in QOL, as measured by the FACT-G, compared to those in the placebo group (P = 0.05). This effect remained after controlling for age and other factors. Fluoxetine patients also had significant improvements on the Brief Zung self-rating depression scale compared to placebo patients (P = 0.0002). Treatment had no effect on spiritual well being or on survival.
‘‘Only the most depressed patients [those who scored ³ 4 on the two-question screening survey] seemed to benefit from fluoxetine’’ in terms of quality of life and depression, Dr. Fisch said. This group included two thirds of the patients in the study. During the discussion period, Dr. Fisch pointed out that the prevalence of depression in the overall population of cancer patients is unknown but is believed to range from 25% to over 40%. Data previously presented at ASCO by his group indicated that about 25% of unselected patients showed a two-question screening score (> 4) that would place them in the subgroup most likely to benefit from treatment.
"This is the largest controlled trial comparing an antidepressant to placebo in advanced cancer patients, and one of the first therapeutic trials in cancer patients involving the longitudinal assessment of spiritual well-being," Dr. Fisch said. "Results of the two-question screening survey may help predict which patients are most likely to benefit from treatment with fluoxetine."
"These data should encourage all of us to screen our patients for depression," commented Patricia Ganz, MD, of the UCLA School of Medicine and Public Health, Jonsson Comprehensive Cancer Center in Los Angeles. The discussant for the presentation, she added, "This study shows that it is feasible to screen, and this should become the standard of care."