June 8, 2016

expert reaction to antidepressant use in children and teens

While major depressive disorder is one of the most common mental disorders in children and adolescents, the use of pharmacological intervention to treat it remains controversial. A meta-analysis published in the Lancet reported that of 14 different antidepressants trialled in children, only one was significantly more effective than a placebo.

Prof. Shirley Reynolds, Director of the Charlie Waller Institute, University of Reading, said:

“Depression is a major health problem experienced by around 6% of young people under 18. It has many negative effects on every day activities including school, friendships, family life and hobbies and social activities. It is associated with increased risk of self-harm and suicide and predicts mental health problems and difficulties later in life. Providing prompt effective treatment for adolescent depression is therefore a high priority for research and treatment.

“This paper provides a comprehensive and careful review of evidence that has been collected internationally. The authors of the review have taken a systematic approach to finding evidence, carefully weighing up its strengths and weaknesses, and combining data from different studies to provide a summary of all the available evidence.

“The review specifically examines data from 34 separate studies of 14 different kinds of anti-depressant medication. Over 5000 children and teenagers aged 9 – 18 years were included.  In each study the anti-depressant medication was compared to a placebo (sugar pill) or to another type of anti-depressant medication. Young person, their parents and the researchers did not know which person got what kind of medication or who was given the placebo. Importantly, the positive effects (e.g. reduced symptoms) and negative effects (e.g. self harm) of treatment, and the acceptability of treatment were all examined.

“This kind of study is important because it combines evidence from different countries, collected by researchers working independently from each other. This means that the data are likely to be more reliable and trustworthy and to be more widely relevant. However, an important limitation of reviews of his type is that the authors can only include studies that they are able to find. In this review 65% of studies were funded by companies who make and sell the drugs.  Some studies are never published and they cannot therefore be included. This can introduce bias because studies that highlight harmful effects of anti-depressant medication or show that antidepressant medication does not have positive effects may be more likely to be unpublished. The result of this is that the available data presents an unbalanced picture.

“Based on the available data the authors of this review concluded that the only medication that should be used to treat depression in under 18s is fluoxetine. Fluoxetine was the only type of medication that was significantly better than a placebo in reducing symptoms of depression. It did not increase suicidal behaviours and fewer young people stopped taking fluoxetine because of negative side effects. The study also showed that fluoxetine reduced the symptoms of depression in children and young people but that the size of the reduction was relatively modest.

“This important study confirms and reinforces current UK NICE guidance for the treatment of depression in children and young people.  NICE guidance recommends caution in the use of anti-depressant medication for children and young people. It specifically states that the only anti-depressant that should be prescribed to anyone under 18 years is fluoxetine. It also states that fluoxetine should only be prescribed by a specialist child and adolescent psychiatrist and the young person must closely supervised throughout treatment.

“For most children and young people with depression NICE recommends treatment using psychological therapies.   Specific psychological therapies including Cognitive Behaviour Therapy and Interpersonal Therapy are recommended.  These are associated with reductions in the symptoms of depression but, like fluoxetine, are only moderately effective. Psychological therapies should be delivered by qualified psychological therapists, who receive appropriate supervision and work in a multi-disciplinary team.  This is important to ensure that young people are monitored closely and that any increase in risk is managed. Where patients do respond to psychological therapies or do not want to have psychological therapy anti-depressant medication (only fluoxetine) can be offered.

“Young people and children, and their families should always be involved in making decisions about the treatment they receive. It is important that the risks and benefits of all the treatment options are discussed with them, by a child and adolescent mental health professional. Once in treatment their symptoms, risk of self-harm and suicide, and well-being should be monitored at every treatment session and this should be discussed with them and help guide treatment.”

Dr Bernadka Dubicka, Vice Chair, Faculty of Child and Adolescent Mental Health, Royal College of Psychiatrists, said:

“The paper by Cipriani and colleagues is a careful analysis of the potential risks and harms of antidepressant medication in children and adolescents, and builds on previous meta-analyses. The principle finding, that the best evidence for safety and effectiveness is for fluoxetine, remains consistent with the UK 2005 NICE guidelines.

“We would concur with the additional conclusions that the evidence base for treatment in children and adolescents remains insufficient, and therefore only limited conclusions can be drawn from this data. In addition, many trials have excluded the most suicidal and at risk young people; this study also excluded young people with treatment resistant depression, therefore we are still unclear about the risks and benefits of antidepressants in young people who are the most impaired.

“We agree with the authors’ conclusions that antidepressants should be used judiciously, monitored carefully, and the risks and benefits assessed in each individual case. However, in those young people with a highly impairing and potentially life-threatening depressive disorder, where non-pharmacological interventions have not been successful, then pharmacological treatment remains an important treatment option.”

‘Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis’ by Cipriani et al. published in The Lancet on Wednesday 8^th June. 

Declared interests

Prof. Shirley Reynolds: “My post at the University of Reading is partly funded by the Charlie Waller Memorial Trust and Berkshire NHS Foundation Trust. I am co-director of the Oxford Academic Health Science Network Anxiety and Depression programme.  I have received grant funding for research from NIHR and MRC.”

Dr Bernadka Dubicka: “BD is a co-author on a psychosocial treatment manual for depression which is licensed to Lundbeck.”