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 (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
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