Antidepressant pharmacogenetics in children and young adults: A systematic review

Antidepressants are frequently prescribed and are the first-line pharmacological treatments for psychiatric disorders in children and adolescents. Although antidepressants are generally effective and well-tolerated by children, between 31% to 48% will not respond and up to 25% will experience an adverse drug reaction. Evidence from adult populations suggests pharmacogenetic information can assist with identifying individuals at greatest risk for poor response or adverse drug reactions but the evidence base in pediatric populations is less clear.

We systematically identified, reviewed, and critically evaluated the antidepressant pharmacogenetics literature among children and adolescents using standardized tools and consensus criteria.

We identified 24 studies, most of which were of fair to moderate quality. Collectively, the studies identified 25 significant gene-antidepressant associations involving 10 genes (ABCB1, BDNF, CYP2C19, CYP2D6, FKBP5, GNB3, HTR1B, HTR2A, SLC6A4, TPH2) and nine antidepressants (amitriptyline, citalopram, escitalopram, fluoxetine, fluvoxamine, nortriptyline, paroxetine, sertraline, and venlafaxine). None of the identified associations have been independently replicated in children.

Included studies were heterogenous in terms of study design, genes and drugs assessed, and outcomes measured.

The antidepressant pharmacogenetics knowledge base in pediatric populations is still emerging, but results to date echo many of the gene-antidepressant associations identified in adult populations. Given ubiquitous prescribing of antidepressants in the care of children and adolescents with psychiatric disorders, further research on identifying new and confirming current gene-antidepressant associations are warranted.