SSRI Has Little Benefit in Depressed Cancer Patients

Antidepressants can counter depression, lessen fatigue, and improve the quality of life of cancer patients who have a major depression, researchers have reported.

However, a study of one SSRI, sertraline, showed that it did not help advanced cancer patients whose depressive symptoms are less severe.

It was headed by Martin Stockler, M.D., a medical oncologist and associate professor of cancer medicine and clinical epidemiology at the University of Sydney in Australia. Results were published in the June 4 early online publication of The Lancet Oncology.

This randomized, double-blind, placebo-controlled, multicenter included 189 patients with advanced cancer. All had filled out a Patient Disease and Treatment Assessment Form while visiting their oncologists. The form asked the patients to evaluate themselves on seven aspects of well-being on a scale of 0 to 10. Zero meant “no trouble at all,” 1 through 3“ mild,” 4 through 6 “moderate,” 7 through 9“ severe” and 10 “the worst I can imagine.” All had given themselves a score of 4 or higher regarding depression, anxiety, and fatigue—a criterion for participating in the study.

None, however, was thought by his or her oncologist to have major depression. Oncologists recruiting patients for the trial had been instructed that if they suspected that any patients had major depression, they should refer them to the psychiatrist at their center who was participating in the trial. If the patients were found by the psychiatrist to have major depression, they were treated and not recruited into the study.

Half of the 189 subjects were assigned to receive, on a daily basis, 50 mg of the SSRI antidepressant sertraline, and half were assigned to receive a placebo, to be continued indefinitely. Concomitant anticancer treatments as well as supportive treatments—for example, the prescribing of opioids or antiemetics, or referral to a psychologist, social worker, or palliative-care team—were given according to standard local practice.

Subjects were evaluated at the start of the trial and at four, eight, 12, 16, 26, 39, and 52 weeks later for depression, anxiety, fatigue, and overall quality of life.

Multiple instruments were used to document outcomes. For example, the Center for Epidemiologic Studies Depression scale, a validated yardstick for identifying depression in the general population, was used to evaluate depression in the subjects. The Hospital Anxiety and Depression Scale, which assesses anxiety and depression in those who are medically ill, was used to evaluate anxiety. At the start of the study one-fourth of the subjects had scores on the Center for Epidemiologic Studies Depression scale consistent with clinical depression, and 8 percent had scores on the Hospital Anxiety and Depression Scale consistent with anxiety.

Subjects were also assessed on length of survival, which was calculated from the date of their randomization into the trial to the date of their death from any cause. Finally, results for the antidepressant and control groups were compared.

Antidepressant treatment was found to have no significant benefit over a placebo in reducing subjects' depression, anxiety, or fatigue, or in improving their overall quality of life, at four or eight weeks after the trial started. The same was the case when results from four and 12 weeks into the trial were compared and when results from four and 52 weeks were compared. In fact, even subjects with the worst scores at the start of the study did not appear to benefit from taking sertraline. The only advantages that sertraline seemed to confer over placebo were in reducing irritability, cough, sleep difficulties, and “difficulty in looking after myself.”

When assessing survival duration, the researchers found no significant difference between the antidepressant group and the placebo group. Moreover, the groups did not differ in the number of deaths due to cancer progression or in the number of deaths occurring earlier than expected.

Thus “sertraline did not improve symptoms, well-being, or survival in patients with advanced cancer who did not have a major depression,” the researchers concluded, “and should be reserved for those with a proven indication.” They also noted their doubt “that a higher dose of sertraline, or a different SSRI, would have been more effective in our target population.” “However, we cannot rule out these possibilities,” they acknowledged.

“This well-conducted study from Australia points out the problems of control of psychological symptoms in advanced cancer that stem from the cancer itself and psychological responses,” Jimmie Holland, M.D., chair of psychiatric oncology at Memorial Sloan-Kettering Cancer Center in New York City, told Psychiatric News. “The absence of a significant effect is disappointing, but we know that pro-inflammatory cytokines, which are elicited by the immune system in advanced illness, contribute heavily to fatigue and depressive systems as well as [a shortened] survival.”

The trial was funded by the Cancer Councils of New South Wales and South Australia, National Health and Medical Research Council of Australia, Cancer Institute of New South Wales, and Pfizer, Inc. Pfizer had no input into the study's design or outcome.

An abstract of “Effect of Sertraline on Symptoms and Survival in Patients with Advanced Cancer, but Without Major Depression: A Placebo-Controlled Double-Blind Randomized Trial” is posted at<www.thelancet.com/journals/lanonc/article/PIIS1470204507701481/abstract?iseop...>.▪