Clinical Review of Mania, Hostility and Suicide-related Events in Children and Adolescents Treated with Antidepressants

Background: Recent controversy surrounding the use of non-tricyclic antidepressants and the emergence of suicide-related events, hostility/behavioural activation and mania in youth with depression warrants an exploration of the results from randomized controlled trials (RCTs) and published case reports for the emergence of these adverse events.

Objective: To provide a clinical review of the available evidence from RCTs and case reports regarding the safety of nontricyclic anti-depressants in youth with depression.

Methods: Seven RCTs of antidepressant use in youth with depression, four case reports of suicide-related adverse events, three case reports of hostility/behavioural activation, and 12 case reports of precipitation of mania were reviewed.

Results: The majority of patients with suicide-related adverse events from both RCTs and published case reports were suicidal before the start of antidepressant treatment. Hostility/behavioural activation generally developed within days to weeks after the start of antidepressant treatment; in the majority of cases, symptoms resolved within four weeks of dosage lowering or discontinuation of the medication alone. Rates for precipitation of mania from RCTs ranged from 0% to 6%. In approximately 60% of published case reports, manic symptoms resolved with the discontinuation or lowering of the dosage of medication alone.

Conclusions: Several trends were observed in the association between adverse events and the use of nontricyclic antidepressants in youth. When prescribing antidepressants to youth, clinicians should closely monitor patients and fully inform them and their families of the risks and benefits of treatment with antidepressants.