Systematic review
Effects of psychological therapies compared to antidepressant medication alone, or in combination with psychological therapies for depression in children and adolescents: a systematic review
Systematic review
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Key message
One in 20 Norwegian children may have such severe depressive symptoms that they can be diagnosed with depression. Psychological therapy has been the first choice of treatment, but recently antidepressant medications are more frequently used in the treatment of depression in children.
The Norwegian Directorate of Health asked the Knowledge Centre in the Norwegian Institute of Public Health, Knowledge Centre for an update of a Cochrane review published in 2014. We were asked to update two questions: For children and adolescents with depressive symptoms or depression what is the effect of psychological therapy compared with:
- antidepressants alone,
- antidepressants in combination with psychological therapy?
We included three randomized controlled trials with a total of 481 children and adolescents with depression or depression symptoms.
We found no differences in symptoms of depression or other outcomes when comparing the effectiveness of psychological therapy with antidepressants alone or antidepressant medications in combination with psychological therapy.
We have very little confidence in the documentation and cannot say for certain which the most effective form of treatment is.
Summary
Background
According to the Norwegian Institute of Public Health, at any given time, one in 20 Norwegian children have so severe depressive symptoms that they could be diagnosed with depression. Depression may increase the risk of substance abuse and self-harm. The symptoms of depression vary, but can be a persistent feeling of sadness, worthlessness, suicidal thoughts, lack of joy or lack of energy.
Psychological therapy is usually the first choice in the treatment of children and adolescents with depressive symptoms or depression. A recently published systematic review found no clear evidence that psychological therapies, including cognitive behavioral therapy, was effective for children under 12 years with depression. There are several therapies such as cognitive behavioral therapy, mentalization based therapy, behavior therapy, interpersonal therapy, solution-focused therapy and psychoeducational therapy. Antidepressant drugs are also offered to children and youth. In recent years, selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants have been used in the treatment of depression in some children and adolescents. Two of 100 children and adolescents (under 19 years) use antidepressants. A recently published network meta-analysis on the effects of several different antidepressants concluded that fluoxetine probably has the best effect.
We were asked to update the analyses for two questions from a previously Cochrane-review published in 2014 about the effectiveness of psychological therapy compared with antidepressants alone or in combination with psychological therapy for children and adolescents with depression.
Method
We used the search strategy of the Cochrane authors and searched the CENTRAL database in September 2016. We searched for randomized controlled trials from 2013 to 2016. We had the following inclusion criteria:
Population: Children with depression
Action: Psychological therapy
Comparison: Antidepressant drugs alone, or antidepressant medications combined with psychological therapy
Outcome: Depression, remission, drop out, suicidal thoughts and functioning.
Result
We went through 866 titles and abstracts from the database search. We read ten articles in full text. Nine of these were excluded because they were either protocol to an ongoing study, or they studied adults, or it was not a randomized controlled trial.
Our findings are based on three studies from Romania, USA and Australia with a total of 481 children with depression between 11 and 18 years. The studies were published in 2004, 2006 and 2015. Children who were suicidal were excluded, however most children also had other psychiatric diagnoses such as anxiety disorders. The three included studies examined the effects of cognitive behavioral therapy. The children in Romania and Australia received sertraline, whereas in the US they received fluoxetine. The Romanian study only measured the outcomes at end of treatment with no long-term follow-up. The other trials had follow-up data for up to one year after treatment.
Regarding the effect of psychological therapy compared with antidepressant medications for depression, the average depression symptoms was 0.5 higher in the group receiving psychological therapy (from 2.74 lower to 3.74 higher measured at Reynolds Adolescent Depression Scale that goes from 30 to 120) measured 12 months after treatment and 0.16 standard deviations higher measured immediately after treatment (from 0.35 lower to 0.68 higher). For dropout from treatment, the odds ratio was 0.83 (from 0.38 to 1.79) measured at end of treatment and 1.17 (0.63 to 2.19) 6-9 months after treatment. Regarding suicidal ideation (measured with suicidal ideation questionnaire Junior High School version) the average suicidal ideation was 2.5 lower (from 5.09 lower to 0.09 higher) after 12 months in the group receiving psychological therapy.
Regarding the effect of psychological therapy compared with antidepressant medications in combination with psychological therapy, the mean depression symptom was 3.1 lower measured at Reynolds Adolescent Depression Scale that goes from 30 to 120 (from 6.38 lower to 0.18 higher) for the group receiving the combination of psychological therapy and antidepressants, and 0.16 standard deviations lower measured immediately after treatment (from 0.97 lower to 0.64 higher). For dropout from treatment, the odds ratio was 0.96 (95% confidence interval 0.27 to 3.41) measured at end of treatment and 0.75 (0.40 to 1.42) 6-9 months after treatment. Regarding the suicidal thoughts the average suicidal ideation was 0.9 higher (from 1.37 lower to 3.17 higher) (measured with suicidal ideation questionnaire Junior High School version) after 12 months in the group receiving psychological therapy combined with antidepressants.
All trials had high risk of bias, mainly due to lack of blinding of participants, healthcare providers and those assessing the outcomes. All the studies included too few children to establish certainty in the effect estimates. We also have very little confidence in the results, partly because all effect estimates are uncertain with wide confidence intervals.
Discussion
We found three studies that had assessed the impact of psychological therapy compared with antidepressants alone or in combination with psychological therapy. The studies have compared active treatments. We found no differences between the various forms of therapies and it is difficult to say what is the most effective of the various therapies or combinations thereof. One limitation is that we found few studies with few participants and even when we merged the studies together in meta-analyses we have uncertainty about the overall effect estimates.
Research must have long enough follow-up time to determine whether participants will be better in the long term. Only two of the three studies had measured differences in effects over time. It will be difficult to detect improvement when one study only measures the effect right after 16 weeks of treatment.
In our update of the two questions from the Cochrane review, we searched for new randomized controlled trials. The available Cochrane-review had two included trials. The study we found was published in 2015, but included children in 2007. There are ongoing studies so it is possible that in future reviews, we can draw more certain conclusions.
Conclusion
With data from three randomized controlled trials in which a total of 481 children between 11 and 18 years participated, we cannot say anything definitely about the effect of psychological therapy compared with antidepressants alone or antidepressant medications in combination with psychological therapy for children and adolescents with depression or depression symptoms.
