Pharmacogenetic study focused on fluoxetine pharmacodynamics in children and adolescent patients: impact of the serotonin pathway

Pharmacogenet Genomics. 2016 Nov;26(11):487-496. doi: 10.1097/FPC.0000000000000240.

Abstract

Objective: Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics.

Patients and methods: The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways.

Results: Clinical improvement after treatment with fluoxetine in our pediatric population was associated significantly with two polymorphisms located in genes related to the serotonergic system: the 5-hydroxytryptamine receptor 1B (HTR1B) and the tryptophan 5-hydroxylase 2 (TPH2).

Conclusion: Although a wide range of candidate genes related to different pathways were assessed, the results show that genetic markers directly related to serotonin have an important effect on fluoxetine response.

MeSH terms

  • Adolescent
  • Anxiety Disorders / drug therapy
  • Child
  • Depressive Disorder / drug therapy
  • Female
  • Fluoxetine / administration & dosage
  • Fluoxetine / pharmacokinetics*
  • Fluoxetine / pharmacology
  • Humans
  • Male
  • Mental Disorders / drug therapy*
  • Obsessive-Compulsive Disorder / drug therapy
  • Pharmacogenomic Testing / methods
  • Pharmacogenomic Variants*
  • Receptor, Serotonin, 5-HT1B / genetics*
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics*
  • Treatment Outcome
  • Tryptophan Hydroxylase / genetics*

Substances

  • HTR1B protein, human
  • Receptor, Serotonin, 5-HT1B
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • TPH2 protein, human
  • Tryptophan Hydroxylase