Purpose: Dextofisopam is a non-serotonergic agent thought to modulate autonomic function via a novel hypothalamic receptor, resulting in decreased stimulated autonomic activity. We explored the effects of dextofisopam on bowel function in patients with IBS.
Methods: Men and women with diarrhea-predominant or alternating IBS (d-IBS or a-IBS) were randomized to receive 12 weeks of dextofisopam 200 mg BID or placebo in a double-blind study conducted in the US. Stool frequency and stool consistency were the principal measures of bowel function.
Results: Of 140 patients, 66 received dextofisopam and 74 placebo, 73% were women, and 78% had d-IBS.
Dextofisopam decreased stool frequency and improved stool consistency relative to placebo. These effects were apparent in d-IBS patients, but not in alternators. At Week 12, dextofisopam-treated d-IBS patients had a 70% greater reduction in stool frequency and approximately twice the improvement in stool consistency vs. placebo. In d-IBS patients, decreased stool frequency and improved stool consistency were apparent within 2 days. Interestingly, patients entering the study with higher stool frequency (≥3 stools/day) exhibited a marked reduction in stool frequency, while those who entered the study with lower stool frequency (<3 stools/day) did not. Similar rates of adverse events were seen in the dextofisopam and placebo groups. Worsening abdominal pain occurred more frequently with dextofisopam (12%vs. 4%), and headache occurred more frequently with placebo (5%vs. 12%). Importantly, dextofisopam produced minimal constipation (3.0%, vs. 1.4% for placebo).
Taken together, these data suggest that dextofisopam may be an agent that "normalizes" stool parameters rather than one that retards or stimulates gastrointestinal transit.
Conclusion: Rapid reduction in stool frequency and improvement in stool consistency were seen in d-IBS patients treated with dextofisopam. Though a substantial effect was seen on stool frequency, a very low rate of constipation was seen with dextofisopam. Dextofisopam may be "normalizing" gastrointestinal motility rather than inhibiting motility.
Dextofisopam shows promise of providing an important new therapeutic alternative for IBS, one that may normalize bowel function without producing significant constipation.