Cancer patients often experience both depression and fatigue, and physicians have had good reason to think that relieving depression might also reduce fatigue. But a new large randomized trial has disproved that theory and shifted researchers' attention to other possible strategies to fight cancer-related fatigue.

Fatigue is a serious problem for at least 70 percent of cancer patients, said Gary R. Morrow, Ph.D., of the University of Rochester, N.Y., who reported the findings at the annual meeting of the American Society of Clinical Oncology (ASCO) in San Francisco on May 14. (Note: the final data were subsequently published in the Dec. 15, 2003, issue of the Journal of Clinical Oncology.)

Unlike normal fatigue, cancer-related fatigue is not relieved by rest and often interferes with everyday activities. The study included 738 chemotherapy patients who had reported fatigue. They were randomly assigned to receive either a placebo or 20 mg of Paxil (paroxetine), a common anti-depressant. Paxil belongs to a class of drugs called selective serotonin re-uptake inhibitors, or SSRIs, which reduce depression by lowering levels of serotonin, a brain chemical. The researchers had theorized that the SSRI might also reduce fatigue, since biological clues have suggested that serotonin might be involved in both ailments.

"It all made perfect sense," said Morrow. "It seemed to fit a lot of what we had observed and a lot of what we know. It just happened to be inaccurate."

The results showed that while the Paxil patients had significantly less depression than those who received a placebo, there was little difference in levels of fatigue between the two groups.

"It appears unlikely that serotonin is involved as a common mechanism for both fatigue and depression," Morrow said. He concluded that the question was "not worth further study."

Other strategies to fight fatigue in cancer patients include a drug called ATP, which was developed initially for AIDS-related fatigue and is given intravenously. Another is Ritalin, a psycho-stimulant known for its use in attention deficit disorder.

Drugs to boost red-blood cells production, such as Procrit, are useful in patients with chemotherapy-related anemia, but anemia is not involved in most cases of cancer fatigue, Morrow said. In the Paxil study, fewer than 25 percent of the chemotherapy patients had anemia.

While the study strongly suggested that SSRIs do not affect cancer-related fatigue, the findings have provided useful information, offering evidence that while "fatigue and depression often co-occur in cancer, they may not be caused by the same factors," said Patricia Ganz, M.D., who discussed the trial when it was presented at ASCO.

SSRIs had been considered one of the most promising agents to fight cancer fatigue, Morrow said. The new finding, therefore, may shift the research focus to other agents. Some currently under study include steroids, which are used in chronic fatigue syndrome, and an antihistamine known as loratidine, which looked promising in an early trial that was also reported at ASCO.

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