Depression Affects Survival in Cancer Patients

Roxanne Nelson

September 18, 2010

September 14, 2009 — The presence of depression might adversely affect outcomes in cancer patients. According to the findings of a meta-analysis, published online September 14 in Cancer, depression is a small but significant predictor of mortality in cancer patients.

Among patients experiencing depressive symptoms, mortality rates were up to 26% higher (unadjusted risk ratio [RR], 1.25; 95% confidence interval [CI], 1.12 - 1.40; P < .001) and among patients diagnosed with major or minor depression were up to 39% higher (unadjusted RR, 1.39; 95% CI, 1.10 - 1.89; P =.03) than those without these symptoms.

Conversely, depressive symptoms did not appear to significantly predict disease progression.

"Our meta-analysis did show an increased risk of risk of death in patients who report more depressive symptoms than others, and also in patients who have been diagnosed with a depressive disorder, compared with patients who have not," said first author Jillian R. Satin, MA, a doctoral student in clinical psychology at the University of British Columbia in Vancouver.

However, she emphasized that this study only shows that a link exists. "We cannot prove with this evidence that depression actually causes the increase in mortality," she told Medscape Oncology. "More research will be needed in order to potentially conclude this."

It is never too early in the course of cancer for patients to begin a dialogue with their physicians about mental-health issues.

A certain level of distress is expected after the diagnosis of cancer, Ms. Satin explained. "In our study, we restricted our analysis to studies that measure depression at least 1 month after diagnosis," she said. "Therefore, this is the time frame that our study makes conclusions about."

It can be difficult to define what a "normal" response to a cancer diagnosis looks like, Ms. Satin added, "but it is never too early in the course of cancer for patients to begin a dialogue with their physicians about mental-health issues."

Inconclusive Evidence Prompts Meta-Analysis

Depression has been widely studied in cancer patients, and is the most commonly studied psychological variable with respect to cancer progression and mortality in this population, the authors report. Depression is also the only psychological condition that is more commonly found in cancer patients than in the general population, and is the psychological problem most likely to persist throughout the illness trajectory.

The authors also point out that "a plausible model exists to link depression with cancer progression and mortality through both behavioral and biological pathways." An example is chronic activation of the hypothalamo-pituitary–adrenal axis, which has been implicated as a possible mediator of the effect of depression on disease progression in cancer. Depression has also been associated with inflammation, as previously reported by Medscape Oncology.

Although cancer patients and oncologists believe that psychological variables can influence the course of cancer, the evidence remains inconclusive. For this reason, Ms. Satin and colleagues conducted a meta-analysis to evaluate the extent to which depressive symptoms and major depressive disorder predict disease progression and mortality in cancer patients.

Depression Linked to Mortality but Not Progression

To examine the effects of depression on survival, the researchers identified 27 observational studies (n = 9417), conducted from 1990 to 2009, which met all of their inclusion criteria. Of this group, 25 independent studies were based on measures of depressive symptoms, 3 were based on major or minor depression, 16 evaluated survival at less than 5 years postdiagnosis, and 11 examined survival at 5 years postdiagnosis or more.

"There is no evidence that the effect weakens when adjustments are made for other known risk factors, suggesting that depression may be an independent risk factor in cancer mortality, rather than merely correlating with biological factors associated with a poor prognosis," they write.

Only 3 studies were available for an analysis of the risk for depression on cancer progression, and depressive symptoms did not significantly predict disease progression (unadjusted RR,= 1.23; 95% CI, 0.85 - 1.77; P = .28).

The authors found it "surprising" that depression appeared to predict mortality but not disease recurrence, and postulated that the difference was primarily due to the limited number of studies in their analysis and the corresponding low power.

Recommendations for Future Research

Although this meta-analysis presents reasonable evidence that depression modestly predicts survival in cancer patients, the researchers note that they are unable to reach firmer conclusions because of the different methodologies used to assess psychological variables. These variables limit the generalizability of the research and its ultimate translation into practice.

With these limitations in mind, they propose the following recommendations for future research:

  • The hazard ratio is considered to be a better measure of effect size than the odds ratio or risk ratio because it takes multiple end points into account.

  • Depression should be measured and analyzed at multiple time-points.

  • Whenever possible, cancer-specific mortality should be reported separately from all-cause mortality so that conclusions can be drawn about the direct impact of depression on cancer outcome.

  • Studies with large sample sizes for specified cancer subtypes are required to test the potential moderating effects of variables such as cancer stage, cancer grade, sex, and age.

  • Although depression is the most commonly studied psychological variable with respect to cancer outcomes, it does not follow that it necessarily has the strongest effect on survival or disease severity.


While writing this review, Ms. Satin was supported by a personnel award from the Michael Smith Foundation for Health Research, and one of her coauthors, Wolfganag Linden, PhD, was supported by a New Investigator Team grant, Canadian Institutes for Health Research.


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