The Risks and Benefits of Antidepressants to Treat Pediatric-Onset Depression and Anxiety Disorders: A Developmental Perspective

to be screened for indications of bipolarity and their family histories should be screened for similar features. Caution is warranted also because antidepressants given to children and adolescents are associated with increased rates of suicidal ideation [11–13] and AEs characterized by excessive emotional arousal or behavioral activation. This realization led the US Food and Drug Administration, as well as British and European regulators, to issue a Public Health Advisory in 2004 announcing a multi-pronged strategy to warn the public about the increased risk of suicidal thoughts and behavior (‘suicidality’) in children and adolescents being treated with antidepressant medications [3] . Consequently, a frank and open discussion with family members and other involved healthcare providers concerning the risks and benefits of prescribing antidepressants in childhood is needed. Practitioners and families need to consider all treatment modalities, including nonpharmacologic interventions like cognitive-behavioral therapy (CBT) [4, 14] . This may be particularly true for young children with depressive symptoms. For example, Bridge et al. [11] , in a meta-analysis of pediatric antidepressant treatment involving data from nearly 6,000 children and adolescents, were unable to detect a pooled risk difference in response greater than zero in children younger than the age of 12 years treated for major depressive disorder with SSRIs; this was, in part, due The use of antidepressants to treat children and adolescents with depression or anxiety disorders is widespread, particularly in the USA [1, 2] , and is a continuing source of controversy and concern [3–5] . The systematic review by Offidani et al. [6] provides a sobering and compelling reminder that the use of these agents in children and adolescents is associated with a substantial risk of adverse effects (AEs) characterized by excessive emotional arousal or behavioral activation including mania and hypomania [7–10] . Based on data from more than 6,000 subjects gleaned from antidepressant trials in juvenile depressive (n = 17) and anxiety disorders (n = 25), they documented that at least 10% of these children and adolescents with either a primary depressive or anxiety disorder experienced AEs characterized by excessive arousal activation. These rates were 3 to 10 times higher than observed during treatment with placebo. Cases of ‘mania or hypomania’ were reported in 8% of the children and adolescents on antidepressants compared to just 0.17% of those treated with placebo. Despite the many limitations to this systematic review, the message from the authors is clear. We must be vigilant. We must encourage child and adolescent psychiatrists and other practitioners (pediatricians and primary care professionals), at minimum, to be cautious in the prescribing of selective serotonin-reuptake inhibitors (SSRIs) to children and adolescents [3–5] . Patients need Received: October 29, 2012 Accepted after revision: November 1, 2012 Published online: March 21, 2013