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Depression (PDQ®): Supportive care - Health Professional Information [NCI] - Intervention

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The meta-analysis that led to the initial boxed warning in pediatric patients concluded that the antidepressants are associated with a twofold increase in suicidal ideation and behavior compared to the placebo in children and adolescents.[14] A major meta-analysis published in the Journal of the American Medical Association reanalyzed the data from the child and adolescent studies (including seven studies not included in the initial meta-analysis), using a random-effects model.[15][Level of evidence: I] While this reanalysis found an overall increased risk of suicidal ideation/suicidal behavior consistent with the initial meta-analysis, the pooled risk differences were found to be smaller and statistically insignificant.

Concerns have been raised that the unintended consequence of the warnings will be overly restricted use of antidepressants among those who benefit the most and, hence, an increase in suicidality that the warning seeks to prevent. A study examining U.S. and Dutch data suggests a drop in selective serotonin reuptake inhibitor (SSRI) prescriptions for children and adolescents since the boxed warning was issued and a simultaneous increase in suicide rates in this patient population.[16]

In summary, the risk/benefit equation favors appropriate use of antidepressants with careful monitoring for suicidality. It is important to note that none of the studies that led to the boxed warning included or focused on patients being treated for cancer. Clinical experience and results of small clinical trials suggest that antidepressants can be safely administered to adult cancer patients, although there are no large controlled clinical trials to support this position. When antidepressants are prescribed for patients with cancer, a careful monitoring plan should be implemented by individuals with expertise, and consultation referral should be made for patients who do not respond as anticipated or who present other concerns.

Interferon-related depression

Most antidepressant prescribing is directed at the treatment of an existing depressive disorder or significant depressive symptoms. One study, however, supports the use of antidepressants to prevent depression in patients receiving high-dose interferon for adjuvant therapy of malignant melanoma.[17][Level of evidence: I] The rationale for this approach is that treatment with high-dose interferon is associated with a particularly high rate of depression in this patient population, and proinflammatory cytokines implicated in the biological changes that result in depression may be directly reduced by antidepressants. In this double-blind study of patients receiving high-dose interferon, 2 of 18 patients in the paroxetine group developed depression during the first 12 weeks of therapy, compared with 9 of 20 patients in the placebo group (relative risk [RR] = 0.24; 95% confidence interval [CI], 0.08–0.93). Moreover, there were significantly fewer treatment discontinuations in the paroxetine group (5% vs. 35%, RR = 0.14; 95% CI, 0.05–0.85). Further study is required to confirm these findings and to determine whether prophylactic use of antidepressants has benefit in other treatment settings.

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