Antidepressants Carry Equal Risks




For nearly a decade, the public has heeded warnings of suicidal behavior related to antidepressant use in children and adolescents. However, the use of antidepressants in this population is still increasing. Initially, selective serotonin reuptake inhibitors (SSRIs), the most common class of antidepressants prescribed for children, were the only drugs associated with the increase in suicidal behavior. Now, a large cohort study published in a recent issue of Pediatrics reports that there is no difference in the risk of suicidal behavior among different SSRIs or difference classes of antidepressants.

The United States Food and Drug Administration (FDA) issued a public warning in October 2004 that cautioned about an increase in suicidal thoughts and behaviors in children and adolescents taking SSRIs. Later, the FDA required a “black box warning” — the most serious type of warning available — be placed on the labeling of SSRIs detailing the increased suicidal risks. The warning came after a 2007 study in the Journal of the American Medical Association found that the risk of suicidal thoughts and attempts in young patients taking SSRIs was twice the rate of patients taking placebo.

However, many patients, parents and prescribers were skeptical of the results and the use of SSRIs in children and adolescents has continued to increase over the past several years. Several studies and reviews since the issuance of the FDA’s warning have not duplicated the increased suicidal behavior, and many clinicians and patients feel that the benefits of antidepressant therapy outweigh the risks. A landmark study funded by the National Institute of Mental Health, the Treatment for Adolescents with Depression Study (TADS), concluded that a combination of fluoxetine (an SSRI) and psychotherapy is the most effective treatment for depression in young patients.

Several studies have also analyzed the relationship between antidepressant use in adults and suicide risk, but have yielded conflicting results. Further, several large studies found no increase in suicidal behavior in young people, either.  One study even reported that SSRI use was associated with decreased suicidal behavior in children and adolescents.

To date, most attention has focused on the risk factors associated with SSRI use in children and adolescents, but the current Pediatrics study evaluated several SSRIs, as well as tricyclic antidepressants and other new agents. Overall, the study evaluated a cohort of nearly 21,000 patients aged 10 to 18 years at treatment initiation. During the first year of treatment, there were 266 attempted and 3 completed suicides in the cohort. There was no difference in suicide risk among any of the antidepressant medications investigated.

Children and adolescents with depressive disorders are at increased risk for suicidal thoughts and actions compared to peers with no depressive disorders. Untreated depression can lead to significant, and life-threatening, emotional, psychological and social consequences. The choice of therapy needs to be individualized and based on the history and preferences of the patient and family. All patients with depressive disorders should be monitored for increased suicidal thoughts and behaviors, regardless of therapy.

The new study still does not address the doubts of many clinicians about the validity of the association between antidepressants and suicide, but it does level the playing field of drug choice. But, is the fact that all antidepressants pose an equal risk of suicide good news or bad news? The good news is that it makes all drugs available for treatment, rather than singling out an entire class of drugs as unusable. The bad news is that no one knows how or why these drugs increase the risk of suicidal behavior.  The news, however, does make health care providers and families more aware of careful monitoring of patient response to therapy for depressive disorders. No drug is entirely safe, and no treatment is effective for all patients.

References

Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, & Brent DA (2007). Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA : the journal of the American Medical Association, 297 (15), 1683-96 PMID: 17440145

Gibbons RD, Hur K, Bhaumik DK, & Mann JJ (2006). The relationship between antidepressant prescription rates and rate of early adolescent suicide. The American journal of psychiatry, 163 (11), 1898-904 PMID: 17074941

Hetrick S, Merry S, McKenzie J, Sindahl P, & Proctor M (2007). Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents. Cochrane database of systematic reviews (Online) (3) PMID: 17636776

Jick H, Kaye JA, & Jick SS (2004). Antidepressants and the risk of suicidal behaviors. JAMA : the journal of the American Medical Association, 292 (3), 338-43 PMID: 15265848

March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J, & Treatment for Adolescents With Depression Study (TADS) Team (2004). Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA : the journal of the American Medical Association, 292 (7), 807-20 PMID: 15315995

Olfson M, Marcus SC, & Shaffer D (2006). Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study. Archives of general psychiatry, 63 (8), 865-72 PMID: 16894062

Schneeweiss S, Patrick AR, Solomon DH, Dormuth CR, Miller M, Mehta J, Lee JC, & Wang PS (2010). Comparative safety of antidepressant agents for children and adolescents regarding suicidal acts. Pediatrics, 125 (5), 876-88 PMID: 20385637

Schneeweiss S, Patrick AR, Solomon DH, Mehta J, Dormuth C, Miller M, Lee JC, & Wang PS (2010). Variation in the risk of suicide attempts and completed suicides by antidepressant agent in adults: a propensity score-adjusted analysis of 9 years’ data. Archives of general psychiatry, 67 (5), 497-506 PMID: 20439831

Simon GE, Savarino J, Operskalski B, & Wang PS (2006). Suicide risk during antidepressant treatment. The American journal of psychiatry, 163 (1), 41-7 PMID: 16390887

Vitiello B, Silva SG, Rohde P, Kratochvil CJ, Kennard BD, Reinecke MA, Mayes TL, Posner K, May DE, & March JS (2009). Suicidal events in the Treatment for Adolescents With Depression Study (TADS). The Journal of clinical psychiatry, 70 (5), 741-7 PMID: 19552869

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Jennifer Gibson, PharmD

Jennifer Gibson, PharmD, is a practicing clinical pharmacist and medical writer/editor with experience in researching and preparing scientific publications, developing public relations materials, creating educational resources and presentations, and editing technical manuscripts. She is the owner of Excalibur Scientific, LLC.
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