Selective serotonin reuptake inhibitors (SSRIs) have been used to treat a variety of neuropsychiatric disorders (depression, obsessive-compulsive disorder, panic disorder, bulimia nervosa). The majority (95%) of the body's serotonin is localized to the gut; thus, it is not surprising that SSRIs are associated with numerous gastrointestinal (GI)-related adverse effects. Despite the wide use of SSRIs, their effects on GI function, specifically GI motility, are ill defined.
The results from in vitro studies of fluoxetine on gastric muscle contractility were reported in Neurogastroenterology and Motility (February 2005). The contractile response of guinea pig stomach muscle strips was dose-dependent, and fundus muscle exhibited a stronger response than antral or pyloric circular muscle. Several serotonin receptor antagonists (atropine, tetrodotoxin, phentolamine, and GR113808, a selective serotonin [5-hydroxytryptamine] type 4 receptor partial agonist) were able to reduce the contractile response to fluoxetine. Atropine had the most dramatic effect, reducing the contractile response by 83% and 73% in the fundus and antral muscle, respectively. Based on the concentrations used in this study, the authors suggest that the serum concentration of fluoxetine in patients treated for psychiatric conditions may be sufficient to trigger adverse GI effects.