Elobixibat Improves Chronic Constipation in Patients With Schizophrenia or Depression

Managing Chronic Constipation in Complex Psychiatric Populations

Chronic idiopathic constipation is a prevalent functional bowel disorder that significantly impairs patient quality of life and places a heavy burden on healthcare systems [1, 2]. While osmotic and stimulant laxatives serve as the standard of care, a significant portion of the population remains refractory to these conventional interventions [3, 1, 4]. Ileal bile acid transporter inhibitors, such as elobixibat, modulate colonic function by increasing the delivery of endogenous bile acids to the colon to stimulate both secretion and motility [5, 6]. Meta-analytic data involving 2,155 patients demonstrate that these agents make patients more than twice as likely to achieve a clinical response compared to placebo (Risk Ratio = 2.65; 95% Confidence Interval: 1.91 to 3.68) [3]. Although these agents significantly increase the frequency of spontaneous bowel movements (stools passed without the use of rescue medications) by a mean of 1.68 per week, data regarding their performance in high-risk psychiatric populations have remained limited [3, 7, 6]. A new multicenter study now provides real-world evidence on the safety and effectiveness of this mechanism in patients with schizophrenia and depression.

Real-World Surveillance of Ileal Bile Acid Transporter Inhibition

The researchers conducted a prospective, multicenter, postmarketing surveillance study in Japan (jRCT1080223950) between June 2018 and May 2022 to evaluate the real-world application of elobixibat. This agent functions by inhibiting the ileal bile acid transporter (a protein responsible for the reabsorption of bile acids in the terminal ileum). By blocking this transport, elobixibat increases the concentration of endogenous bile acids entering the colon, where they act as both an osmotic agent, drawing water into the intestinal lumen, and a stimulant agent that enhances colonic motility. This dual mechanism is particularly relevant for psychiatric patients, as it addresses both the reduced fluid intake and the slowed transit time often induced by psychotropic medications. The study design utilized two distinct observation windows to capture both short-term and long-term data. Patients were monitored from the date of their initial dose for either 55 days in the 4-week treatment groups or 419 days in the 52-week treatment groups. The study population consisted of patients with high clinical complexity, specifically those diagnosed with schizophrenia or depression who were already receiving intensive pharmacological management. In the safety analysis set for the 4-week treatment period, the researchers included 105 patients with schizophrenia and 129 patients with depression. The long-term 52-week safety analysis set comprised 43 patients with schizophrenia and 55 patients with depression. Polypharmacy was prevalent across these cohorts, as 85% to 95% of patients were using antipsychotics, while 40% to 55% were using anxiolytics or sedative-hypnotics, both of which are classes of medication frequently associated with secondary constipation. To determine the clinical utility of ileal bile acid transporter inhibition, the study assessed safety outcomes, specifically adverse drug reactions, alongside multiple effectiveness measures. These effectiveness outcomes included changes in weekly defecation frequency, stool consistency as measured by the Bristol Stool Form Scale (a diagnostic tool that classifies human feces into seven categories based on shape and texture), and the severity of general constipation-related symptoms. By tracking these metrics over the course of a year, the researchers aimed to establish whether the dual osmotic and stimulant effects of elobixibat could provide sustained relief for psychiatric patients whose constipation is often exacerbated by their primary medication regimens.

Sustained Improvements in Defecation Frequency and Stool Consistency

The primary effectiveness analysis demonstrated a rapid and sustained increase in bowel movement frequency across both psychiatric cohorts, addressing a major driver of patient dissatisfaction. In the 4-week schizophrenia group, the mean defecation frequency per week increased from 3.3 at baseline to 5.3 at week 4. A similar trend was observed among patients with depression, where the mean defecation frequency per week rose from 3.0 at baseline to 4.9 at week 4. These improvements were not limited to the initial month of treatment; in the 52-week treatment groups, the mean defecation frequency per week at week 52 remained higher than at baseline, suggesting that the therapeutic effect of ileal bile acid transporter inhibition does not diminish with long-term use in this clinical population. Beyond the frequency of movements, the researchers observed significant shifts in stool quality as measured by the Bristol Stool Form Scale (a clinical metric where a score of 4 represents the ideal 'sausage-like' consistency that is easy to pass). The proportion of patients with an ideal Bristol Stool Form Scale score of 4 increased in all groups by week 2, indicating a rapid normalization of stool consistency. This improvement continued throughout the study period, and the proportion of patients with a Bristol Stool Form Scale score of 4 reached approximately 60% by week 52. Furthermore, the clinical benefit extended to subjective patient experiences, as all constipation-related symptoms improved by week 2 in all groups, providing clinicians with a predictable timeline for symptom relief when initiating therapy in patients with complex psychiatric comorbidities. This rapid onset of action is critical for patient adherence, particularly in populations where cognitive or mood symptoms may interfere with long-term treatment consistency.

Safety Profile and Tolerability in Polypharmacy Contexts

The safety profile of elobixibat is particularly relevant for clinicians managing patients with schizophrenia, who often require complex antipsychotic regimens that contribute to gastrointestinal dysmotility through anticholinergic pathways. In this postmarketing surveillance study, the researchers found that adverse drug reactions occurred in 4.76% of the 4-week schizophrenia group and 2.33% of the 52-week schizophrenia group. These low rates of adverse events suggest that the medication is generally well tolerated over both short-term and extended treatment periods in this specific psychiatric population, even when used alongside potent psychotropic medications. Similar tolerability was observed among patients with depression, a group frequently prescribed anxiolytics or sedative-hypnotics that can exacerbate constipation. The study reported that adverse drug reactions occurred in 3.88% of the 4-week depression group and 9.09% of the 52-week depression group. Across all cohorts, diarrhea was the most common adverse drug reaction in each group, a finding that aligns with the drug's mechanism of action as an ileal bile acid transporter inhibitor (a substance that increases the delivery of bile acids to the colon to stimulate fluid secretion and motility). Crucially for practitioners concerned with drug-drug interactions and systemic safety in polypharmacy contexts, there were no serious adverse drug reactions reported during the surveillance period. This lack of severe complications, combined with the localized action of the drug within the intestinal lumen, provides a favorable safety margin for patients with significant psychiatric comorbidities. The findings indicate that elobixibat can be integrated into existing treatment plans for schizophrenia or depression without introducing substantial new safety risks or compromising the management of the underlying psychiatric condition, offering a viable alternative for patients who have failed traditional laxative therapies.

References

1. Bassotti G, Usai–Satta P, Bellini M. Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. Clinical and Experimental Gastroenterology. 2021. doi:10.2147/ceg.s256364

2. Bassotti G, Satta PU, Bellini M. Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. Clinical and Experimental Gastroenterology. 2021. doi:10.2147/CEG.S256364

3. Suprianto I. Redefining the Therapeutic Ladder in Refractory Chronic Constipation: A Systematic Review and Meta-Analysis of the Role of Ileal Bile Acid Transporter (IBAT) Inhibitors. 2025. doi:10.37275/bsm.v9i9.1381

4. Luthra P, Camilleri M, Burr N, Quigley E, Black C, Ford A. Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis.. The Lancet Gastroenterology and Hepatology. 2019. doi:10.1016/S2468-1253(19)30246-8

5. Nakajima A, Seki M, Taniguchi S, et al. Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial.. The lancet. Gastroenterology & hepatology. 2018. doi:10.1016/S2468-1253(18)30123-7

6. Nakajima A, Taniguchi S, Kurosu S, Gillberg P, Mattsson JP, Camilleri M. Efficacy, long-term safety, and impact on quality of life of elobixibat in more severe constipation: Post hoc analyses of two phase 3 trials in Japan.. Neurogastroenterology and motility. 2019. doi:10.1111/nmo.13571

7. Nakajima A, Shoji A, Kokubo K, Igarashi A. A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan. Gastroenterology Research and Practice. 2021. doi:10.1155/2021/5534687