Investigators Rank Treatment Plans for Child and Adolescent Depression


Fluoxetine alone was more effective treating depression than a combination of fluoxetine with cognitive behavioral therapy.

pediatrics, depression, psychiatry

Depressive disorders are prevalent in both children and adolescents, with combinations of antidepressants and psychotherapies generally used in routine clinical practice. However, available evidence on the comparative efficacy and safety of these interventions is inconclusive.

A team, led by Xinyu Zhou, PhD, Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, compared and ranked all the available treatment interventions for the acute treatment of depressive disorders in children and adolescents.

The investigators conducted a systematic review and network meta-analysis of available literature for published and unpublished randomized controlled trials, including placebo-controlled and health-to-head trials of 16 antidepressants, 7 psychotherapies, and 5 combination treatments used for the acute treatment of children and adolescents with depressive disorder.

They also excluded trials recruiting patients with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than 10 patients.

The investigators sought primary outcomes of the change in depressive symptoms and treatment discontinuation due to any cause. The team also estimated summary standardized mean differences (SMD) or odds ratios (OR) with credible intervals (CrI) using network meta-analysis with random effects.

Overall, the analysis included 71 trials involving 9510 participants, the majority of which with moderate to severe depressive disorders.

The investigators found fluoxetine combined with cognitive behavioral therapy was more effective than only CBT (—0.78; 95% CrI, −1·55 to −0·01) and psychodynamic therapy (–1.14; 95% CrI, −2.20 to −0.08).

However, the combination therapy was not more effective than fluoxetine along (-0.22; 95% CrI, -0.86-0.42). In addition, no pharmacotherapy alone was more effective than any psychotherapy administered alone.

The team also identified only fluoxetine with CBT and fluoxetine alone were significantly more effective than pill placebo or psychological controls (SMDs ranged from −1.73 to −0.51) and only interpersonal therapy was more effective than all psychological controls (—1.37 to −0.66).

Nortriptyline (SMDs ranged from 1.04-2.22) and waiting list (SMDs ranged from 0.67-2.08) were less effective than the majority of active interventions.

The investigators also found nefazodone and fluoxetine were linked to fewer discontinuations than sertraline, imipramine, and desipramine (ORs ranged from 0.17-0.50) and imipramine was linked to more discontinuations than pill placebo, desvenlafaxine, fluoxetine with CBT, and vilazodone (2.51-5.06).

The majority of results were rated either “low” or “very low” in terms of confidence of evidence according to the Confidence in Network Meta-Analysis.

“Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents,” the authors wrote. “However, the effects of these interventions might vary between individuals, so patients, carriers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis.”

The study, “Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis,” was published online in The Lancet Psychiatry.

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