What is the US FDA public health advisory for use of tricyclic antidepressants (TCAs) in pediatric populations?

Updated: Mar 18, 2020
  • Author: Derrick Lung, MD, MPH; Chief Editor: Stephen L Thornton, MD  more...
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Answer

Cyclic antidepressants (CAs) have been used in the treatment of major depression since the late 1950s. Originally termed tricyclic antidepressants (TCAs), they are more accurately called cyclic antidepressants because some newer members of this class have a four-ring structure. Cyclic antidepressants have a narrow therapeutic window, which increases their likelihood for toxicity. [1]

In 2018, the US Food and Drug Administration (FDA) issued a public health advisory that directed manufacturers of all antidepressant drugs, including TCAs, to revise the labeling for their products to include a boxed warning and expanded warning statements alerting health care providers to an increased risk of suicidality (suicidal thinking and behavior) in children and adolescents being treated with these agents. [2]

The risk of suicidality associated with these drugs was identified based on a combined analysis of short-term (up to 4mo), placebo-controlled trials of 9 antidepressant drugs in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. A total of 24 trials involving over 4400 patients were included. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients on drug therapy was 4%, twice the placebo risk of 2%. No suicides occurred in these trials. [2]

On the basis of those data, the FDA determined that the following points are appropriate for inclusion in the boxed warning [2] :

  • Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders.
  • Anyone considering the use of an antidepressant in a child or adolescent for any clinical use must balance the risk of increased suicidality with the clinical need.
  • Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior.
  • Families and caregivers should be advised to closely observe the patient and to communicate with the prescriber.
  • A statement regarding whether the particular drug is approved for any pediatric indication(s) and, if so, which one(s).

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