Why Antidepressants Can Cause Gut Pain

Selective serotonin reuptake inhibitors frequently produce significant gastrointestinal side effects.  Nausea was reported by up to 26% of subjects and diarrhea in up to 30% of subjects in a recent review of the new antidepressant vilazodone.  Gastrointestinal side effects tend to be seen with the initiation of antidepressant drugs commonly followed by a period of improved tolerability.

The mechanism for this gastrointestinal effect is poorly understood.   The gut is known to have serotonin receptors.  Some gastrointestinal therapeutic agents target the serotonin receptor as their mechanism of action.  For example, the antinausea drug ondansetron appears to act through it's antagonism of the 5HT (serotonin) 3 receptor.  This results in inhibition of gastric activity while components of activity of the small intestine remain functional.

To better understand the effects of serotonin on GI motility, Janssen and colleagues from the University of Leuven conducted a novel experiment.  Twenty healthy subjects were studied in a GI motility study following administration of placebo and the selective serotonin reuptake inhibitor citalopram.

The authors found that administration of citalopram significant reduced the gastrointestinal transit time compared to that found at baseline and placebo (see chart).

Upper gastrointestinal transit time is composed of three separate phases known as the migrating motor complex of MMC.  Citalopram appeared to reduce the duration of phase 1 and phase 2 while the time spent in phase 3 was unchanged.

The authors attribute the change in transit time to a direct effect of citalopram on GI serotonin receptors although a central CNS effect could not be ruled out.  The speculate this effect may be potentially therapeutic in individuals with constipation predominant irritable bowel syndrome.

This study did not directly address the issue of GI side effects associated with the SSRI antidepressants.  Nevertheless, it suggests acute increased GI transit times with SSRIs may be a mechanism that contributes to GI side effects of nausea, diarrhea, cramping and pain.

Further studies of this effect are needed looking at a longer time frame.  Since most GI side effects improve with prolonged administration, it is possible a receptor compensation mechanism may be involved in changes in side effects over time.

Graph of gastrointestinal transit times is an original graph produced by the author from data in the manuscript.

Janssen P, Vos R, & Tack J (2010). The influence of citalopram on interdigestive gastrointestinal motility in man. Alimentary pharmacology & therapeutics, 32 (2), 289-95 PMID: 20456311