title: Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.
abstract: BACKGROUND
  Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning.
  
  
  OBJECTIVE
  To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes.
  
  
  METHODS
  We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 November 2011. This register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date).
  
  
  METHODS
  RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or 'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria.
  
  
  METHODS
  Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when outcomes were measured on different scales.
  
  
  RESULTS
  We included ten studies, involving 1235 participants in this review. Studies recruited participants with different severities of disorder and with a variety of comorbid disorders, including anxiety and substance use disorder, therefore limiting the comparability of the results. Regarding the risk of bias in studies, half the studies had adequate allocation concealment (there was insufficient information to determine allocation concealment in the remainder), outcome assessors were blind to the participants' intervention in six studies, and in general, studies reported on incomplete data analysis methods, mainly using intention-to-treat (ITT) analyses. For the majority of outcomes there were no statistically significant differences between the interventions compared. There was limited evidence (based on two studies involving 220 participants) that antidepressant medication was more effective than psychotherapy on measures of clinician defined remission immediately post-intervention (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.27 to 0.98), with 67.8% of participants in the medication group and 53.7% in the psychotherapy group rated as being in remission. There was limited evidence (based on three studies involving 378 participants) that combination therapy was more effective than antidepressant medication alone in achieving higher remission from a depressive episode immediately post-intervention (OR 1.56, 95% CI 0.98 to 2.47), with 65.9% of participants treated with combination therapy and 57.8% of participants treated with medication, rated as being in remission. There was no evidence to suggest that combination therapy was more effective than psychological therapy alone, based on clinician rated remission immediately post-intervention (OR 1.82, 95% CI 0.38 to 8.68).Suicide-related Serious Adverse Events (SAEs) were reported in various ways across studies and could not be combined in meta-analyses. However suicidal ideation specifically was generally measured and reported using standardised assessment tools suitable for meta-analysis. In one study involving 188 participants, rates of suicidal ideation were significantly higher in the antidepressant medication group (18.6%) compared with the psychological therapy group (5.4%) (OR 0.26, 95% CI 0.09 to 0.72) and this effect appeared to remain at six to nine months (OR 1.27, 95% CI 0.68 to 2.36), with 13.6% of participants in the medication group and 3.9% of participants in the psychological therapy group reporting suicidal ideation. It was unclear what the effect of combination therapy was compared with either antidepressant medication alone or psychological therapy alone on rates of suicidal ideation. The impact of any of the assigned treatment packages on drop out was also mostly unclear across the various comparisons in the review.Limited data and conflicting results based on other outcome measures make it difficult to draw conclusions regarding the effectiveness of any specific intervention based on these outcomes.
  
  
  CONCLUSIONS
  There is very limited evidence upon which to base conclusions about the relative effectiveness of psychological interventions, antidepressant medication and a combination of these interventions. On the basis of the available evidence, the effectiveness of these interventions for treating depressive disorders in children and adolescents cannot be established. Further appropriately powered RCTs are required.
authors.affiliation: Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia. gcox@unimelb.edu.au
authors.forename: Georgina R
authors.initials: GR
authors.lastname: Cox
authors.forename: Patch
authors.initials: P
authors.lastname: Callahan
authors.forename: Rachel
authors.initials: R
authors.lastname: Churchill
authors.forename: Vivien
authors.initials: V
authors.lastname: Hunot
authors.forename: Sally N
authors.initials: SN
authors.lastname: Merry
authors.forename: Alexandra G
authors.initials: AG
authors.lastname: Parker
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hetrick
mesh_terms: D000293:Adolescent; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000628:therapy; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D003863:Depression / Q000628:therapy*; D006801:Humans; D011613:Psychotherapy / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D019966:Substance-Related Disorders / Q000628:therapy; D059020:Suicidal Ideation
chemical_list: D000928:Antidepressive Agents