Antidepressants and Suicide – What’s Happened Since the Black Box?

 

In 2004, the FDA mandated that all antidepressants carry a black box warning related to the risk of new suicidal behavior.  This warning generated a great deal of attention and controversy leading up to the warning and in its immediate aftermath, as data showed a subsequent drop in antidepressant prescription and an 18% increase in completed adolescent suicides in 2004.  What has happened since then? 

Suicide Rates:  Data is available by the CDC only through 2007.  The increased youth suicide rate seen in 2004 has returned to baseline with 2007 data showing the lowest youth suicide rate in 25 years.  In the Netherlands, however, the youth suicide rate continued to rise in 2004 and 2005 (Gibbons et al., 2007).

Antidepressant Use:  Antidepressant prescriptions were reduced following the black box warning.  A recent study showed that rates remained lower through 2006 (Pamer et al., 2010). 

Black Box Extension:  In 2007, the black box warning was extended to cover individuals 18-24 years old. 

New Studies:  A few more recent clinical trials continue to show a signal of increased suicidal ideation and behavior (although not completed suicides) with SSRI treatment compared to placebo (Barbui et al., 2009). Taking a broader view, Bridge and colleagues reported in JAMA (2007) a meta-analysis of pediatric antidepressant trials using updated information.  They found that the suicide thoughts and behavior difference was smaller between drug (3%) and placebo (2%) than previous reports. They also examined treatment effects and concluded that overall the “benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempts.”  

The Treatment of Adolescents with Depression Study (TADS), perhaps the most extensive study to date on adolescent depression, continues to produce important findings (Reinecke et al., 2009).  Follow-up of the original sample offers hope that treatment works over time and that the combination of evidence-based psychotherapy such as CBT with careful medication use may produce the strongest ratio of benefit to risk. 

A Synthesis: Given the original intensity of the reactions on all sides to the black box warning, it is somewhat surprising that there has been a relative lack of focused follow-up.  What evidence we do have, however, suggests that although most youth will report decreases in suicidal thoughts and thinking, the possibility that a small number will experience new onset of suicidality remains.  This risk needs to be weighed against the finding of relatively good efficacy of antidepressants, especially in more severely depressed youth and in combination with other interventions.

References: 

Barbui, C et al. (2009). Selective serotonin reuptake inhibitors and risk of suicide: A systematic review of observational studies. CMAJ,180:291-297. 

Bridge JA,  et al. (2007). Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment. A meta-analysis of randomized controlled trials. JAMA, 297:1683-1696. 

Gibbons et al. (2007).  Early evidence of the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents.  Am J Psychiatry, 164:1356-1363. 

Pamer C, et al. (2010). Changes in US antidepressant and antipsychotic prescription patterns during a period of FDA actions. Pharmacoepidemiol Drug Safe, 19:158-74. 

Reinecke et al. (2009). Findings from the Treatment of Adolescents with Depression Study (TADS): What have we learned? What do we need to know? J Clin Child Adolesc Psychol, 38:761-767.

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