Childhood and Adolescent (Pediatric) Depression

Primer

Childhood and Adolescent Depression is a subtype of depression characterized by low mood, anxiety, and irritability in children and youth.

Prognosis

Efficacy

  • The most recent study by the Youth Depression Alleviation–Combined Treatment (YoDA-C) found that there was no benefit to adding fluoxetine to cognitive behavioural therapy.[3]
    • Importantly, in contrast to the older Treatment for Adolescents With Depression Study (TADS) study, conducted between 2000 and 2003, the newer YoDA-C study actually implemented a placebo pill in the comparison group.[4]

Treatment

  • Antidepressants should never be a first-line treatment for child/adolescent depression. Recent studies have shown no benefit of adding fluoxetine to CBT in the treatment of even moderate-severe depression.[5]
  • Fluoxetine is generally the first medication choice for pediatric depression because there is FDA approval for MDD (as well as OCD) in youth. It has the most evidence to support efficacy for 
pediatric MDD, especially in children <12 years.
    • Fluoxetine also has a long half-life if non-adherence is a 
concern, which minimizes the risk of withdrawal.
    • Unlike the other SSRIs, it is also available as an oral 
solution (liquid).

  • Citalopram, escitalopram, or sertraline might be picked over fluoxetine if there are potential drug interactions with fluoxetine, or if there are significant concerns about a long half-life agent because the patient 
has risk factors for bipolar disorder.

How Long Should Children and Adolescents Remain on Antidepressants?

Antidepressant treatment length is not well studied in this population, and is based on adult research. General guidelines recommend staying on an antidepressant between 6 to 12 months after achieving remission in those with no prior history of depression.[6] In individuals with multiple episodes or a past history of severe depression, remaining on an antidepressant for at least 1 year is recommended.

Treatment of Major Depressive Disorder in Children and Adolescents

MacQueen, G. M. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. The Canadian Journal of Psychiatry, 61(9), 588-603.
1st line Monotherapy: cognitive behavioural therapy (CBT) or interpersonal therapy (IPT), internet-based psychotherapy (for milder severity, if in-person is not possible)
2nd line Monotherapy: fluoxetine (Level 1)
Monotherapy: escitalopram, sertraline, citalopram* (Level 2)
3rd line† Monotherapy: venlafaxine, tricyclic antidepressants
* = Not recommended in those with congenital long QT syndrome, congenital heart disease, or hepatic impairment, † = Only recommended for adolescents (older than 12 years).

Minimal or Non-response of Treatment to Major Depressive Disorder in Children and Adolescents

MacQueen, G. M. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. The Canadian Journal of Psychiatry, 61(9), 588-603.
1st line Add SSRI to psychotherapy
2nd line Switch to another SSRI (if unresponsive to fluoxetine)
3rd line† Venlafaxine, tricyclic antidepressant
† = Only recommended for adolescents (older than 12 years).

Treatment-Resistant Major Depressive Disorder in Children and Adolescents

MacQueen, G. M. et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. The Canadian Journal of Psychiatry, 61(9), 588-603.
1st line SSRI + psychotherapy
2nd line Switch to another SSRI (if unresponsive to fluoxetine)
3rd line† • Venlafaxine (Level 2)
• TCA (Level 3)
• Neurostimulation treatment (ECT or rTMS)
† = Only recommended for adolescents (older than 12 years).

Antidepressant Withdrawal

Since children have an increased rate of drug metabolism, BID dosing at lower dosages is recommended for all SSRIs except fluoxetine to minimize the risk of daily withdrawal symptoms.

Adverse Events

Suicide

  • One of the most controversial aspects of using antidepressant medications in the pediatric population is the association with increased risk of suicidal behaviour. It is important to note that Health Canada has not approved any antidepressant for use in youth, and the FDA has only approved fluoxetine in the treatment of depression.[7] In 2003, the FDA issued a black-box warning because a meta-analysis found a 1.5 to 2-fold increase in increased suicidal thoughts/behaviours (although there was no increased incidence of suicide deaths).
  • Similarly, observational studies have found an increased risk for suicidal acts including suicide attempts. These findings are opposite of what is seen in other age groups (e.g. - geriatric and older adults) where SSRI use actually shows a decrease in suicidality. Thus, it is important to be vigilant about the use of antidepressants in young adults and the pediatric population and monitor for suicidal behaviours or thoughts.

Resources

Readings

References

1) Wilkinson, P., Dubicka, B., Kelvin, R., Roberts, C., & Goodyer, I. (2009). Treated depression in adolescents: predictors of outcome at 28 weeks. The British Journal of Psychiatry, 194(4), 334-341.
2) Garber, J., & Weersing, V. R. (2010). Comorbidity of anxiety and depression in youth: Implications for treatment and prevention. Clinical Psychology: Science and Practice, 17(4), 293-306.
3) Davey, C. G. et al. (2019). The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial. The Lancet Psychiatry, 6(9), 735-744.
4) PsychiatricNews: Study Finds Little Benefit of Adding Fluoxetine to CBT for Youth
5) Davey, C. G., Chanen, A. M., Hetrick, S. E., Cotton, S. M., Ratheesh, A., Amminger, G. P., ... & Rice, S. (2019). The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial. The Lancet Psychiatry, 6(9), 735-744.
6) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
7) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.