Selective Serotonin Reuptake Inhibitors Can Successfully Treat Depression But Not Fatigue in Cancer Patients

SAN FRANCISCO—The 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 depression."

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 patients—194 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.