Stockler, M. R., O’Connell, R., Nowak, A. K., Goldstein, D., Turner, J., Wilcken, N. R., Zoloft's Effects on Symptoms and survival Time Trial Group. (2007). Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial. Lancet Oncology, 8, 603–612.

The sertraline intervention required patients to take 50 mg/day of the study drug or a matched placebo for the study period. Patients who developed symptoms of major depression were referred to a psychiatrist coinvestigator at the institution. If there was a definite indication for antidepressants or if patients decided to stop the study due to adverse events, the drug was discontinued gradually by reducing the dose to 25 mg/day for one week before stopping. Patient outcomes were assessed at baseline and 4, 8, 12, 16, 26, 39, and 52 weeks.

• The study was comprised of 189 patients with advanced cancer for whom the responsible oncologist doubted benefits of treatment with antidepressants.
• In the sertraline group (n = 95), the male-to-female ratio was 55:40. There were multiple primary cancer sites, and the majority had received prior chemotherapy (n = 78).
• In the placebo group (n = 94), the male-to-female ratio was 56:38. There were multiple primary cancer sites, and the majority had received prior chemotherapy (n = 78).
• Patients were excluded if they had major depression, delirium, coexisting disorders, were taking medications that contraindicated sertraline treatment, or had a history of psychiatric illness.

This was a multicenter trial conducted in the oncology clinics of several Australian hospitals.

Patients were undergoing the active treatment phase of care.

The study was a double-blind, placebo-controlled, centrally randomized trial that was stratified for institution, sex, anticipated future cytotoxic treatment, and Performance Score:

1. Sertraline (n = 95)
2. Placebo control (n = 94).

• Functional Assessment of Cancer Therapy–Fatigue (FACT-F)
• Utility-Based Questionnaire-Cancer (UBQ-C)
• Somatic and Psychological Health Report (SPHERE)

Sertraline had no significant effect in improving fatigue compared to placebo. Outcomes were compared on the basis of scores at baseline and four and eight weeks.

• The study population was poorly defined, and the exclusion criteria of major depression were arbitrary and left to the responsible oncologist.
• The study was closed at the first interim analysis because sertraline showed no benefit to patients.