Effect Of An SSRI Antidepressant On Fatigue And Depression In Seven Hundred Thirty-Eight Cancer Patients Treated With Chemotherapy: A URCC CCOP Study

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: Gary R. Morrow
Affiliation: University of Rochester Cancer Center, Rochester, NY


    Fatigue can significantly interfere with a cancer patient's ability to fulfill daily responsibilities and enjoy everyday life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue. This randomized double blind study was carried out to evaluate such a hypothesis.

Materials and Methods:

  • This study included 738 patients, 194 males (26%) and 544 females (74%) who reported fatigue by day seven following the second of at least four cycles of chemotherapy.
  • Patients were randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil) or an identical-appearing placebo in a double-blind clinical trial.
  • Study medication began between days seven through ten following cycle two and continued until day seven of cycle four.
  • Questionnaires measuring fatigue and depression were completed by patients at home on day seven of cycles two (baseline), three and four
  • Baseline measures of fatigue and depression were comparable for patients in the two study groups.


  • Paroxetine significantly reduced depression during chemotherapy (p <0.01)
  • The antidepressant did not have a significant effect on fatigue (p = 0.06).

Authors' Conclusions

    Study results revealed that Paxil is effective in treating depression during chemotherapy. The lack of a significant effect of this SSRI on fatigue suggests that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.

Clinical/Scientific Implications:

    This is a large, well-done randomized study the shows that depression can be identified and treated in the cancer population. Of note, the authors of this study did not control for physiological causes of fatigue, such as, anemia or febrile neutropenia. They will attempt to do so in the future. This attempt to control for physiological causes of fatigue will help delineate the relationship between depression and fatigue.

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