Efficacy and Safety of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Children and Adolescents

Susan C. Sharp; Jessica A. Hellings


Clin Drug Invest. 2006;26(5):247-255. 

In This Article

Abstract and Introduction

Background: Given the widespread reports involving the use of selective serotonin reuptake inhibitors (SSRIs) in children, the present paper reviews and discusses published double-blind, placebo-controlled studies assessing the safety and efficacy of SSRIs in children and adolescents with major depressive disorder.
Methods: Published and unpublished double-blind, placebo-controlled studies of SSRIs in children and adolescents with depression during the years 1990–2004 were reviewed. A MEDLINE search was performed using the key words 'depression', 'randomised controlled trial', 'SSRIs', 'children' and 'adolescents'. The GlaxoSmithKline website was also searched for relevant studies on paroxetine. Outcome measures were the Clinical Global Impressions scale, the Children's Depression Rating Scale-Revised, the Hamilton Rating Scale for Depression, the depression subscales of the Kiddie Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version, and the Montgomery and Asberg Depression Rating Scale. Adverse effects and withdrawal rates are reported.
Results: There were seven randomised, placebo-controlled trials involving 1619 children and adolescents aged 6–18 years in total. The SSRIs fluoxetine, paroxetine, sertraline and citalopram were reported to exhibit safety and efficacy for treatment of depression in children and adolescents. Reanalysis of published and unpublished studies by the US FDA and the UK's Medicines and Healthcare products Regulatory Agency (MHRA) raised alerts regarding higher suicidal ideation rates from SSRIs in this population. Present guidelines are discussed.
Conclusions: SSRIs remain a first-line pharmacological treatment for depression in children and adolescents for whom psychotherapy has failed or is unavailable. Suicidal ideation and behaviours merit close monitoring. More studies are needed.

Depression in children and adolescents is significant because of its prevalence, morbidity and mortality. It occurs in 2% of children and in 4–8% of adolescents.[1] The lifetime prevalence of major depression in adolescents aged 15–18 years is 13–15%.[2] The disorder predicts impaired social and academic functioning.[3] Depressed adolescents frequently grow up to be depressed adults, requiring more medical and psychiatric hospitalisations.[4] They attempt suicide more often than healthy controls, and have more problems later in life at work, with their families, and socially.[4] While boys and girls manifest an equal sex ratio of depression in childhood, depression rates increase more markedly in girls than in boys during puberty and adolescence.[5]

In 10- to 14-year-olds, suicide is the fourth leading cause of death, and in adolescents, suicide rises to the third leading cause of death.[6] Depression in adolescence is associated with subsequent increased likelihood of tobacco use, greater involvement in deviant activities and accidents, and impaired relationships with parents and partners.[7] The wide range of harmful consequences underscores the importance of early diagnosis and ongoing treatment of depression in children and adolescents.

Research in child and adolescent psychopharmacology is considered to be seriously lacking in comparison with that in adults.[8] Tricyclic anti- depressants (TCAs) were used to treat depression in children prior to SSRI availability. Treatment using TCAs requires close monitoring of patients' blood levels and ECGs for potential adverse effects, and prevention of potentially lethal overdose by having parents and caregivers lock the medication away. In addition, available studies have not found superior efficacy of TCAs over placebo for depression in this young population.[9]

In the past decade, SSRIs have become first-line pharmacological treatment for depressed children and adolescents, particularly for severe cases or those unresponsive to psychotherapy. These agents have been marketed as being less cardiotoxic than TCAs, and as being better tolerated overall and with greater safety in overdose. However, the safety and efficacy of SSRI treatment of children and adolescents with major depression came under closer examination in 2004. There may be an association with possible provoking or worsening of suicidal behaviours and attempts. Death in a child resulting from fluoxetine toxicity has been reported.[10] Lethality in overdose may occur. In addition there may be associated sexual adverse effects including priapism and bleeding tendencies.[11]

This article presents the data from seven published controlled studies on SSRI treatment of child and adolescent depression, and discusses findings from both published and unpublished studies. Updates on advisories and warnings by regulatory agencies are provided and present prescribing guidelines are discussed.


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