Riblet, N., Larson, R., Watts, B.V., & Holtzheimer, P. (2014). Reevaluating the role of antidepressants in cancer-related depression: A systematic review and meta-analysis. General Hospital Psychiatry, 36, 466–473.

DOI Link

doi: 10.1016/j.genhosppsych.2014.05.010

Purpose

STUDY PURPOSE: To determine specific guidances for treating cancer-related depression by examining differences in the efficacy and tolerability of antidepressants in patients with cancer-related depression

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: MEDLINE (n = 4,198, 1948–December 31, 2013); the Cochrane Library (n = 283, 1800–December 31, 2013); PsycINFO (n = 243, inception–December 31, 2013); the Cumulative Index to Nursing and Allied Health Literature (n = 447, 1986–December 31, 2013); ClinicalTrials.gov (n = 7, n.d.–December 31, 2013); abstracts of the American Psychosocial Oncology Society Meetings (n = 0, 2010–2013); reviews of references (n = 0).

KEYWORDS: Cancer, depression, antidepressive agents, treatment tolerability, depressive symptoms

INCLUSION CRITERIA: Randomized, controlled trials (RCTs) or quasirandomized trials of patients with active cancer of any type and stage who had comorbid depression of any severity and were treated with antidepressant medications for a duration of at least four weeks compared to a placebo or no treatment. Studies had to report depression outcomes.

EXCLUSION CRITERIA: Studies of patients whose cancer was in remission so that the focus remained on patients with active malignancies

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 5,178 total references with duplicates removed

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The patients that were included in the review had varying levels of depression severity and various countries of origin. One person, a nonblinded reviewer, screened titles and abstracts, excluding those that did not meet criteria, then screened full-text reviews of the remaining studies to determine the final, eligible studies. A translator was used to translate two foreign-language studies into English.

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED = 9
TOTAL PATIENTS INCLUDED IN REVIEW = 1,169
KEY SAMPLE CHARACTERISTICS: The nine final RCTs were published between 1985 and 2011. Eight of these studies contained a placebo group compared to a group receiving an active drug; one trial compared patients receiving an active drug to patients receiving no treatment. Six studies included multiple cancer types, but three studies reported only patients with breast cancer. Most (83%) of the patients were female, and the mean age of all patients was 54.3 years old. The duration of treatment ranged from 4–12 weeks; attrition was greater than 20% for all but two of the studies.

Phase of Care and Clinical Applications

PHASE OF CARE: Multiple phases of care

APPLICATIONS: Elder care, palliative care

Results

Symptoms of depression were measured using the Hamilton Rating Scale for Depression, the Center for Epidemiologic Studies Depression Scale, the Zung Self-Rating Depression Scale, and the Montgomery-Asberg Depression Rating Scale. The studies compared five antidepressants, mianserin, fluoxetine, paroxetine, amitriptyline, and desipramine, to a placebo. Mianserin was shown to improve symptoms of depression robustly when compared to a placebo after four or more weeks of treatment measured as a continuous or dichotomous variable. Similarly, fluoxetine was shown to improve symptoms of depression versus a placebo with less robust findings. No notable differences were found when fluoxetine was measured as a continuous or as a dichotomous variable. Paroxetine was favored over a placebo after the removal of a small, lower-quality study (n = 35, two groups). Two small studies of amitriptyline (n = 19) and desipramine (n = 35, two groups) showed no significant differences when compared to a placebo. Two studies of paroxetine and one of desipramine compared to a placebo showed no significant differences in depression rates.

Tolerability reporting (measured by dropout rates) was poor, creating a limitation for this measurement. Mianserin showed lower dropout rates compared to a placebo. Two fluoxetine trials showed an increased risk of dropout compared to a placebo even after the removal of the smaller study because of heterogeneity. Three trials of paroxetine showed an increased risk of dropouts compared to a placebo. Studies of desipramine suggested a lower risk of dropouts related to side effects.

Conclusions

The three effective antidepressants were mianserin, paroxetine, and fluoxetine. The mianserin group had a lower dropout rate than the placebo group, but with non-significant difference; higher depression response rate. Paroxetine group had higher dropout rate than placebo but with non-significant difference. The fluoxetine group had a significantly higher dropout rate when compared to a placebo. Paroxetine and fluoxetine were not associated with higher depression response rates when compared to a placebo. The evidence for the efficacy and tolerability of different antidepressants remains scarce for cancer-related depression, suggesting a great need for further randomized, controlled trials with placebo controls.

Limitations

Opening database search dates varied. Heterogeneity among the studies complicated comparisons, causing small sample studies to be left out of at least two analyses. Only nine studies met the final criteria for inclusion, suggesting a need for research addressing the efficacy and tolerability of antidepressant use in patients with cancer and symptoms of depression.

Nursing Implications

Further research in patients with cancer and depression is needed to determine the best treatment guidelines. Mianserin showed the best results in these studies; however, it was reported that it is not available for sale in the United States. Research using other antidepressant drugs is needed. For example, tricyclic antidepressants and monoamine oxidase inhibitors should be studied. Paroxetine and desipramine did not show promising results in reducing depression in these studies.

Legacy ID

4879