A review of the available research points to a lack of clear evidence that antidepressant drugs provide effective treatment for major depressive disorder in children and adolescents.
Major depression is estimated to affect 2.8% of children aged 6 to 12 years, and 5.6% of teens aged 13 to 18; however, the actual number of cases may be even higher since the condition is thought to be under-diagnosed. Symptoms of depression in children can include irritability and aggressive behaviour, and may be difficult to distinguish from other manifestations of ordinary childhood angst. The consequences of depression can be serious – ranging from various forms of social dysfunction to suicide attempts. Thus, the condition is not to be taken lightly.
Treatment options for depression in children and teens typically start with psychotherapy, but increasingly, may also include administration of antidepressant medications. The use of antidepressants for young patients is controversial, however. In 2004, the US Food and Drug Administration (FDA) warned practitioners that antidepressant use in children and adolescents may in fact be associated with an increased risk of suicide.
A study recently published in The Lancet took a comprehensive look at the available literature documenting drug trials and other research related to antidepressant use by children and teens. The purpose of the analysis was to provide a broad-based review of both direct and indirect evidence as to the efficacy of antidepressant drugs prescribed to young people, and to compare data about different drugs in order to evaluate whether certain drugs may be more effective, or have a better risk-benefit profile, than others.
The study involved materials drawn from PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies’ websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015. Overall, 34 trials including 5260 participants and 14 antidepressant medications were included in the review. The particular drugs covered in the literature were amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine.
None of the literature reviewed provided direct comparisons of all drugs to each other. However, a placebo-controlled trial was available for all antidepressant drugs except clomipramine. Five of the 14 drugs were also the subject of a trial in which they were directly compared to at least one other drug. Other trials also provided data about the effectiveness and adverse effects reported for individual drugs.
In analysing this mass of data, the authors of the study published in The Lancet looked at the average overall change in depressive symptoms associated with each drug, as gleaned from the literature, and the proportion of patients who discontinued treatment due to adverse effects of any kind.
Their overall conclusion was that the risk-benefit profile of antidepressant drugs as a group did not seem to offer a clear advantage for children and adolescents in the acute treatment of major depressive disorder. On the available evidence, only fluoxetine appeared to be statistically more effective than placebo in alleviating symptoms of depression. Fluoxetine also appeared to be better tolerated (i.e., fewer cases of discontinued use due to adverse effects) than duloxetine and imipramine, the two drugs against which it could be directly compared on the available data. Patients given imipramine, venlafaxine, and duloxetine had a higher incidence of discontinued use due to adverse effects than patients who were given a placebo.
The authors of the study acknowledge that the evidence used in comparing drugs to each other was in many cases of low quality, due to the nature of the data available and the lack of literature providing head-to-head comparisons for many drugs. In addition, there was also a lack of reliable data on suicide rates associated with many of the antidepressants, making it impossible to assess the risk of suicide from all drugs.
The authors caution that any treatment decision concerning depression in a child or teen should be made carefully, in light of the overall clinical picture, and should always involve close monitoring, regardless of the treatment approach that is selected.
Written By: Linda Jensen