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Meta-Analysis
. 2014 Nov 30;2014(11):CD008324.
doi: 10.1002/14651858.CD008324.pub3.

Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents

Georgina R Cox  1 , Patch Callahan, Rachel Churchill, Vivien Hunot, Sally N Merry, Alexandra G Parker, Sarah E Hetrick
Affiliations
Meta-Analysis

Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents

Georgina R Cox et al. Cochrane Database Syst Rev. .

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.

Objectives: 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.

Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The 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).

Selection criteria: 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.

Data collection and analysis: 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.

Main results: We included eleven studies, involving 1307 participants in this review. We also identified one ongoing study, and two additional ongoing studies that may be eligible for inclusion. 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, just under 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, some trials measured suicidal ideation 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 0.26, 95% CI 0.07 to 0.98), 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.

Authors' 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.

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Conflict of interest statement

There are no known conflicts of interest in this working group.

Figures

1
1
PRISMA flow diagram: CCDANCTR update search June 2014
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.
1.2
1.2. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.
1.3
1.3. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.
1.4
1.4. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.
1.5
1.5. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 5 Dropouts (post‐intervention).
1.6
1.6. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 6 Dropouts (six to nine months follow‐up).
1.7
1.7. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 7 Suicidal ideation (post‐intervention).
1.8
1.8. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 8 Suicidal ideation (six to nine months follow‐up).
1.9
1.9. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).
1.10
1.10. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).
1.11
1.11. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).
1.12
1.12. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 12 Remission by cut‐off (post‐intervention).
1.13
1.13. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 13 Remission by cut‐off (six to nine months follow‐up).
1.14
1.14. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 14 Remission by cut‐off (12 months follow‐up).
1.15
1.15. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
1.16
1.16. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).
1.17
1.17. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).
1.18
1.18. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 18 Depression symptoms self rated (post‐intervention).
1.19
1.19. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).
1.20
1.20. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 20 Depression symptoms self rated (12 months follow‐up).
1.21
1.21. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 21 Functioning (post‐intervention).
1.22
1.22. Analysis
Comparison 1 Psychological therapy versus antidepressant medication, Outcome 22 Functioning (six to nine months follow‐up).
2.1
2.1. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.
2.2
2.2. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.
2.3
2.3. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.
2.4
2.4. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.
2.5
2.5. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 5 Remission by clinical interview (12 months follow‐up).
2.6
2.6. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 6 Dropouts (post‐intervention).
2.7
2.7. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 7 Dropouts (six to nine months follow‐up).
2.8
2.8. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 8 Dropouts (12 months follow‐up).
2.9
2.9. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).
2.10
2.10. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).
2.11
2.11. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).
2.12
2.12. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 12 Suicidal ideation (post‐intervention).
2.13
2.13. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 13 Suicidal ideation (six to nine months follow‐up).
2.14
2.14. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 14 Suicidal ideation (12 months follow‐up).
2.15
2.15. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 15 Remission by cut‐off (post‐intervention).
2.16
2.16. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 16 Remission by cut‐off (six to nine months follow‐up).
2.17
2.17. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 17 Remission by cut‐off (12 months follow‐up).
2.18
2.18. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
2.19
2.19. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).
2.20
2.20. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).
2.21
2.21. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 21 Depression symptoms self rated (post‐intervention).
2.22
2.22. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 22 Depression symptoms self rated (six to nine months follow‐up).
2.23
2.23. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 23 Depression symptoms self rated (12 months follow‐up).
2.24
2.24. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 24 Functioning (post‐intervention).
2.25
2.25. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 25 Functioning (six to nine months follow‐up).
2.26
2.26. Analysis
Comparison 2 Combination therapy versus antidepressant medication, Outcome 26 Functioning (12 months follow‐up).
3.1
3.1. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 1 Remission by clinical interview (post‐intervention) ITT.
3.2
3.2. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 2 Remission by clinical interview (post‐intervention) OC.
3.3
3.3. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.
3.4
3.4. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.
3.5
3.5. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 5 Dropouts (post‐intervention).
3.6
3.6. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 6 Dropouts (six to nine months follow‐up).
3.7
3.7. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 7 Suicidal ideation (post‐intervention).
3.8
3.8. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 8 Suicidal ideation (six to nine months follow‐up).
3.9
3.9. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 9 Suicidal ideation (post‐intervention).
3.10
3.10. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 10 Suicidal ideation (six to nine months follow‐up).
3.11
3.11. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 11 Suicidal ideation (12 months follow‐up).
3.12
3.12. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 12 Remission by cut‐off (post‐intervention).
3.13
3.13. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 13 Remission by cut‐off (six to nine months follow‐up).
3.14
3.14. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 14 Remission by cut‐off (12 months follow‐up).
3.15
3.15. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
3.16
3.16. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).
3.17
3.17. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).
3.18
3.18. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 18 Depression symptoms self rated (post‐intervention).
3.19
3.19. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).
3.20
3.20. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 20 Depression symptoms self rated (12 months follow‐up).
3.21
3.21. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 21 Functioning (post‐intervention).
3.22
3.22. Analysis
Comparison 3 Combination therapy versus psychological therapy, Outcome 22 Functioning (six to nine months follow‐up).
4.1
4.1. Analysis
Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 1 Dropouts (post‐intervention).
4.2
4.2. Analysis
Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 2 Suicidal ideation (post‐intervention).
4.3
4.3. Analysis
Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 3 Remission by cut‐off (post‐intervention).
4.4
4.4. Analysis
Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 4 Remission by cut‐off (12 months follow‐up).
4.5
4.5. Analysis
Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
4.6
4.6. Analysis
Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 6 Depression symptoms self rated (post‐intervention).
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Update of

References

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TORDIA 2008 {published data only}
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References to ongoing studies

Craighead 2012 {published data only}
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Davey 2012 {published data only}
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Gunlicks‐Stoessel 2013 a {published data only}
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Gunlicks‐Stoessel 2013 b {published data only}
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