Suicide risk of antidepressant medication
Over the past few years, significant concerns have been raised about the risk of suicidal thinking and behavior with the use of antidepressants in children, adolescents, and young adults. Since 2003, U.S. and European regulators have issued several public health warnings on this topic. The first such advisory issued by the U.S. Food and Drug Administration (FDA) warned about a possible association between antidepressants and suicidal thinking and behavior in children and adolescents. In December 2003, the Medicines and Healthcare Products Regulatory Agency of the United Kingdom issued a letter to doctors advising against the use of antidepressants in anyone younger than 18 years. In October 2004, the FDA mandated pharmaceutical companies to add a "black box" warning to the labeling of all antidepressants suggesting increased risk of suicidality in pediatric patients who were taking antidepressants. The FDA revised this boxed warning in May 2007 to include young adults younger than 25 years. The new, carefully worded warning emphasizes that the risk of suicidality is associated with both antidepressants and depression. In addition to raising concerns about increased suicidality in children, adolescents, and young adults, the warning acknowledges a significant protective effect of antidepressants in adults aged 65 and older.
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. 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.[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.
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.