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CME

Are the SSRIs and Atypical Antidepressants Safe and Effective for Children and Adolescents?

  • Authors: Tim Kendall ; Steve Pilling ; Craig J Whittington, PhD
  • THIS ACTIVITY HAS EXPIRED
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Target Audience and Goal Statement

This activity is intended for primary care physicians, psychiatrists, and other specialists who treat children and adolescents with depression.

The goals of this activity are to update physicians on the controversies around SSRIs and atypical antidepressants for the treatment of major depression in children and adolescents, and to provide a treatment guide based on recent recommendations.

Upon completion of this activity, participants will be able to:

  1. List the SSRIs and atypical antidepressants that have been studied for the treatment of major depressive disorder (MDD) in children and adolescents.
  2. State concerns of the MHRA and FDA about the use of these products for MDD in adolescents and children.
  3. Identify the shortcomings of published trials on antidepressant use in children and adolescents.
  4. Describe the FDA review of suicidality risk with the use of these products.
  5. Compare the efficacy of cognitive behavioral therapy with and without fluoxetine with placebo in MDD in children and adolescents.


Disclosures

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Medscape encourages Authors to identify investigational products or off-label uses of products regulated by the U.S. Food and Drug Administration, at first mention and where appropriate in the content.


Author(s)

  • Tim Kendall

    CORE, Sub-department of Clinical Health Psychology, University College London, London, United Kingdom

    Disclosures

    Disclosure: Tim Kendall has reported no financial relationships relevant to this educational activity.

  • Steve Pilling

    CORE, Sub-department of Clinical Health Psychology, University College London, London, United Kingdom

    Disclosures

    Disclosure: Steve Pilling has reported no financial relationships relevant to this educational activity.

  • Craig J Whittington, PhD

    Sub-department of Clinical Health Psychology, University College London, London, United Kingdom

    Disclosures

    Disclosure: Craig J. Whittington, PhD, has reported no financial relationships relevant to this educational activity.


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    For Physicians

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    Medscape designates this educational activity for a maximum of 0.5 category 1 credit(s) toward the AMA Physician's Recognition Award. Each physician should claim only those credits that reflect the time he/she actually spent in the activity.

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For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

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CME

Are the SSRIs and Atypical Antidepressants Safe and Effective for Children and Adolescents?

Authors: Tim Kendall ; Steve Pilling ; Craig J Whittington, PhDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

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Abstract and Introduction

Abstract

Purpose of Review: This article summarizes recent developments in the use of selective serotonin reuptake inhibitors and atypical antidepressants to treat children and adolescents with depression at a time when their use in this context has generated considerable controversy and confusion for clinicians, patients and their families. Recent reports and recommendations from drug regulators in the UK and the US are discussed, alongside other reviews and recently published randomized controlled trials.
Recent Findings: It is now widely accepted that these drugs increase the risk of suicide-related behaviours and although recently published trials have been more positive, a metaanalysis of published and unpublished trials has cast doubt about efficacy. The evidence for publication bias in the studies considered is also raised and the implications discussed. There is some evidence, however, that the combination of psychological treatment with fluoxetine may be both effective and protective against the increased risk of suicide-related behaviours, although problems over blinding suggest further research is needed to clarify this potentially positive combination treatment.
Summary: Current evidence supports the conclusions of the UK drug regulator in warning against the use of all the newer antidepressants except fluoxetine in this age group, and alternative therapies should be sought in the first instance. Caution is needed in interpreting drug company sponsored trials given the evidence of selective reporting and publication bias. Combining fluoxetine with a psychological treatment such as cognitive-behavioural therapy is also worth considering.

Introduction

This paper reviews the current evidence for the safety and efficacy of the selective serotonin reuptake inhibitors (SSRIs) and atypical antidepressants (venlafaxine, nefazodone and mirtazapine) in the treatment of major depressive disorder (MDD) in children and adolescents. This has been the subject of considerable controversy involving the pharmaceutical industry, the regulatory authorities and clinical and academic experts in both Europe and North America.[1*,2*] In the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) advised that the SSRIs citalopram, escitalopram, paroxetine, and sertraline, and the related antidepressant venlafaxine are contraindicated as new treatment in those under 18 years of age with depressive illness.[3] The MHRA also advised that fluvoxamine should not be used to treat depression in the under 18s because of a lack of information on safety and efficacy. More recently, the Food and Drug Administration (FDA) has directed all antidepressant drug manufacturers to label their products with a 'black-box' warning about the increased risk of suicidality (suicidal thinking and behaviour).[4]

Although there now appears to be general agreement between the MHRA and the FDA that the SSRIs and atypical antidepressants carry the risk of increasing suicidality in depressed children and adolescents, there is much less agreement as to whether or not they are efficacious as antidepressants in this context. Most recently published reviews and trials suggest that these drugs are associated with either a small additional improvement over and above placebo or have no added benefit. However, doubts about efficacy have been variously explained as the result of poor study design,[5] poor quality of the evidence,[6*] insufficient data,[7] differences in study methodology,[8] or studying the wrong groups of children.[5]

This uncertainty is further complicated by the failure to publish trials, sponsored by the pharmaceutical industry, which have negative findings. This has led to publication bias and distorting the evidence base upon which judgements about safety and efficacy are ordinarily made in clinical practice.[9**] The role of the pharmaceutical companies in withholding negative trial data has been the focus of considerable criticism,[10] and has no doubt contributed towards the decision of the International Committee of Medical Journal Editors to now insist upon pre-trial registration of all trials as a condition of later publication of the findings.[11]

In this article we will first briefly look at the background to the regulatory decisions, then examine the reviews and trials of SSRIs and atypical antidepressants in the treatment of childhood depression published since July 2003, with a particular focus upon the issue of efficacy.