Antidepressants have Limited Efficacy in Juvenile Depression

Forest plot of rate ratios (RR, with 95% CI) of responses to drug or placebo in 30 randomised double-blind placebo-controlled comparisons of rates of ‘response’ to antidepressants v. placebo, with overall pooled RR (1.22; 95% CI 1.15–1.31; blue diamond)
A recent systematic review and meta-analysis shows that at worse antidepressants are not effective for juvenile depression and at best better research might proof this conclusion wrong.
Juvenile meaning depression among children and adolescents.

The figure above is the forest plot of this systematic review:Forest plot of rate ratios (RR, with 95% CI) of responses to drug or placebo in 30 randomised double-blind placebo-controlled comparisons of rates of ‘response’ to antidepressants v. placebo, with overall pooled RR (1.22; 95% CI 1.15–1.31; blue diamond).

Antidepressants of all types showed limited efficacy in juvenile depression, but fluoxetine might be more effective, especially in adolescents. Studies in children and in severely depressed, hospitalised or suicidal juvenile patients are needed, and effective, safe and readily accessible treatments for juvenile depression are urgently required.

  • there were 30 contrasts arising from 29 randomised controlled trials for meta-analysis
  • All studies included provided drug doses consistent with contemporary paediatric practice, based on body-weight-adjusted daily dosing (mg/kg) considered standard for treating adult major depressive disorder
  • average exposure time of 8.7 weeks (median=8, range 1–12)
  • primary outcomes for meta-analysis a priori as responder status, based on changes in clinical ratings from intake to last observation point (as defined in each trial) involving substantial improvement, typically a 50% or greater reduction in symptomatic ratings of depression on standardised scales. This is a weak outcome measure, remission should be the aim of treatment mostly defined as a score of 7 or lower on the Hamilton Depression Rating Scale
  • pooled overall effect size, based on meta-analysis to determine a pooled rate ratio and its confidence interval for all 30 trials, yielded a value of 1.22 (95% CI 1.15–1.31)
  • There was no difference in efficacy between different antidepressant classes such as SSRI’s or TCAs. Moreover analysis fail to support the possibility that SRIs may be superior in efficacy to tricyclic antidepressants
  • The three age groups yielded an interesting progression in rate differences and corresponding decreases of NNT by age (about 21 for children, 10 juveniles of mixed ages and 8 for adolescents)

Explanations for the disappointing results:

  • Relatively high rates of response to placebo or other non-specific interventions
  • Age-inappropriate or insufficiently sensitive outcome measures
  • Inadequately powered trials
  • Adverse case selection (e.g. minimally ill, uncertain or heterogeneous diagnoses, previous treatment failures, poorly cooperative participants)
  • Incomplete control of substance misuse
  • Inadequate dosing or duration of treatment
  • Simple lack of efficacy in juvenile v. adult mood disorders

My opinion is that selection of juveniles with relatively heterogeneous illnesses can explain the lack of efficacy. Maybe only juveniles with melancholic or psychotic depression respond to antidepressants. This is comparable to depression in adults.

sampling of young patients with depression may include a high proportion of relatively mildly ill patients, who have most probably never received in-patient treatment, and who are more likely to improve spontaneously with or without additional effects of placebo treatment

Moreover, it remains to be seen whether the brain of juveniles is as susceptible to antidepressants as with adults. Depression in a developing brain may be different from depression in an adult brain and the influence of antidepressants on a developing brain might be lacking. This is supported by the finding in this meta-analysis that older juveniles respond better than younger ones. Here is a video about teens and their developing brain, thanks PsychCentral

Importantly, prepubertal children with depression may differ biologically from adolescents or adults, and it remains unclear whether depression in prepubertal children is a substantially different disorder from that found in adolescents or adults, perhaps including developmental differences in either the pharmacodynamics of antidepressants or in their clinical effects.

Related posts on this blog:
Adolescents Brain and Depression
Finally some good news about antidepressants and adolescents
7 Posts about Adolescents and Depression
FDA Warning doesn’t put Youth at Increased Risk
Tsapakis*, E.M., Soldani*, F., Tondo, L., Baldessarini, R.J. (2008). Efficacy of antidepressants in juvenile depression: meta-analysis. The British Journal of Psychiatry, 193(1), 10-17. DOI: 10.1192/bjp.bp.106.031088