SAN FRANCISCOThe theory that serotonin might mediate both
depression and fatigue in cancer patients was debunked by results of a
community-based study involving more than 700 cancer patients. Reporting on
behalf of the University of Rochester Cancer Center Community Clinical Oncology
Program (CCOP), Gary R. Morrow, MD, said, "Our data suggest that it is
unlikely that serotonin is involved as a final common pathway for fatigue and
Debilitating fatigue is reported by up to one half of cancer
patients at some point during diagnosis, treatment, or recovery. Because
fatigue commonly co-exists with depression in patients undergoing chemotherapy,
the theory arose that administration of an antidepressant that alleviates
symptoms of depression should also reduce fatigue. If indeed serotonin mediated
both depression and fatigue, then the selective serotonin reuptake inhibitors (SSRIs)
should help both problems.
In the Rochester study, patients randomized to receive the SSRI
paroxetine (Paxil) had significantly less depression during cancer chemotherapy
than those randomized to placebo (P < 0.01), but there was no
significant effect on fatigue.
The double-blind study included 738 patients194 males (26%)
and 544 females (74%)from 188 different private medical oncology practices
affiliated with the CCOP. "This trial was not done in a tertiary center.
It was done in the community," Dr. Morrow emphasized.
All Had Reported Fatigue
The patients enrolled in the study had reported fatigue by day
7 following the second of at least four cycles of chemotherapy. Patients were
randomly assigned to receive either 20 mg of paroxetine or an identical-looking
placebo, beginning between days 7 through 10 following cycle two and continuing
until day 7 of cycle four.
Questionnaires measuring fatigue were completed at home by
patients on day 7 of cycles two (baseline), three, and four (outcome). The
Multidimensional Assessment of Fatigue (MAF), Profile of Mood States (POMS),
and Fatigue Symptom Checklist (FSCL) were used to measure fatigue and the POMS
and Center for Epidemiologic Studies-Depression (CES-D) to measure depression.
Baseline measures of fatigue and depression were comparable for patients in the
two study groups.
"This study demonstrates that we can successfully treat
depression in cancer patients, but there was absolutely not one hint of effect
on fatigue," Dr. Morrow said.
More Effective Strategy
Fatigue affects 70% of cancer patients and may persist for
months and even years after patients are off therapy, reported Patricia Ganz,
MD, of the UCLA School of Medicine and Public Health, Jonsson Comprehensive
Cancer Center in Los Angeles. "This study suggests that addressing
physiological and treatment-related factors may be a more effective strategy
for control of fatigue than use of SSRIs," continued Dr. Ganz, who served
as discussant for the presentation.
"Questions that might be raised include: How were medical
issues controlled in these patients? How many patients had febrile neutropenia
or were given white cell growth factors? Was erythropoietin given? What level
of anemia was controlled for?"
She pointed out that anemia, neutropenia, hypothyroidism, and
electrolyte problems can all be direct causes of fatigue in cancer patients.