Most patients with disorders of gut‐brain interaction receive pharmacotherapy with major or moderate drug‐gene interactions

Abstract

Background

How variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut‐ brain interaction is unclear.

Aims

To assess the prevalence of pharmacogenomics‐predicted drug‐gene interactions and symptom outcomes for patients with disorders of gut‐brain interaction.

Methods

Patients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing. The change in symptoms from baseline to 6 months was compared for patients with variations in CYP2D6 and CYP2C19, which metabolize neuromodulators, and SLC6A4, which encodes the sodium‐ dependent serotonin transporter.

Results

At baseline, 79 of 94 participants (84%) had at least one predicted major drug‐ gene interaction, and all 94 (100%) had at least one predicted moderate interaction. For the 44 participants who completed a survey of their symptoms at 6 months, the mean (SD) irritable bowel syndrome‐symptom severity score decreased from 284 (71) at baseline to 231 (95) at 6 months ( p < 0.001). Among patients taking selective serotonin reuptake inhibitors, the decrease in symptom severity ( p = 0.03) and pain ( p = 0.002) scores from baseline to 6 months was greater for patients with a homozygous SLC6A4 long/long genotype (n = 30) (ie, increased serotonin transporter activity) than for patients with homozygous short/short or heterozygous long/short genotypes ( n = 64). Symptom outcomes were not affected by CYP2D6 or CYP2C19 variations.

Conclusions

The homozygous SLC6A4 long/long genotype confers better symptom resolution for patients with disorders of gut‐brain interaction who take selective serotonin reuptake inhibitors than do the homozygous short/short or heterozygous long/short genotypes.