Evaluation and Treatment of Constipation in the Geriatric Population.

Chronic constipation affects one-third of the US population and occurs disproportionately in the elderly and female individuals, increasing in older individuals who are institutionalized. This condition has a significant impact on health care costs and quality of life. Clinicians need to consider primary as well as secondary causes of constipation in elderly individuals because the cause is often multifactorial. Diagnostic algorithms should eliminate red-flag symptoms that may indicate a malignancy but also consider pelvic floor dysfunction, which is more common in this age group. An appropriate treatment plan is tailored to the severity of the patient's symptoms.

Impact of patient and disease characteristics on the efficacy and safety of eluxadoline for IBS-D: a subgroup analysis of phase III trials.

BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent gastrointestinal (GI) disorder with a varied presentation, often overlapping with other GI and non-GI disorders. Eluxadoline is a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of IBS-D in adults. As IBS-D is a heterogeneous disease, factors such as patient demographics, symptom severity, and symptom pattern history can potentially inform treatment selection. METHODS: Here, we report additional prospectively planned analyses of two large double-blind, placebo-controlled studies (IBS-3001 and IBS-3002) enrolling patients meeting Rome III criteria for IBS-D. Patients were randomized 1:1:1 to receive placebo or eluxadoline 75 mg or 100 mg twice daily. Efficacy (abdominal pain, stool consistency, and composite, simultaneous improvement in both) and safety were assessed for prospectively defined patient subgroups stratified by age, sex, race, presence of comorbidities, and baseline disease characteristics. RESULTS: Across all age, sex, race, comorbidity, and disease characteristic subgroups, a greater proportion of patients were composite responders with both eluxadoline doses as compared with placebo, including patients with a history of depression or a history of gastroesophageal reflux disease. Among patients aged ⩾65 years, a greater proportion of patients receiving eluxadoline 75 mg were composite, abdominal pain, and stool consistency responders compared with those receiving 100 mg. The proportion of patients with at least one adverse event was slightly higher in patients aged ⩾65 years and also in female patients. CONCLUSIONS: This analysis suggests that eluxadoline is effective in treating IBS-D across a range of commonly encountered patient types. In contrast to the overall population, patients aged ⩾65 years demonstrated a greater proportion of responders at the lower approved 75 mg eluxadoline dose.

Current and emergent pharmacologic treatments for irritable bowel syndrome with diarrhea: evidence-based treatment in practice.

Irritable bowel syndrome with diarrhea (IBS-D) is a common, chronic functional gastrointestinal disorder with symptoms that can be distressing for patients and often result in substantially impaired quality of life. This review focuses on providing clinicians with information on practical, evidence-based treatment for IBS-D. Current therapies commonly used for the treatment of IBS-D, including pharmacologic and nonpharmacologic interventions, are briefly reviewed, followed by discussion of the emergent pharmacologic treatments (rifaximin and eluxadoline) and medical foods (IBgard® and EnteraGam®). Given the lack of a standard treatment algorithm for IBS-D and the emergence of new pharmacologic therapies, treatment needs to be tailored to the individual patient and take into account the severity of disease. In this context, the latter part of this manuscript examines how treatments for IBS-D can be used in clinical practice by presenting three patient case scenarios with varying degrees of IBS-D severity. For each case, the patient's medical history and clinical presentation are related to the Rome Foundation multidimensional clinical profile (MDCP) and potential treatment options with current and emergent therapies are reviewed. The interplay of gastrointestinal symptoms and their psychosocial impact, as well as the importance of a patient-centered approach to therapy, are discussed. Consideration is given to the potential need for combination therapies and how emergent treatments could fit into the treatment pathway for mild, moderate, and severe cases of IBS-D in clinical practice.

An Open-Label Pilot Study of Duloxetine in Patients With Irritable Bowel Syndrome and Comorbid Major Depressive Disorder.

Major depressive disorder (MDD) and irritable bowel syndrome (IBS) frequently co-occur, yet treating their comorbid presentation is challenging. Low-dose tricyclic antidepressants are efficacious for IBS, but higher doses to treat depressive symptoms present tolerability problems, whereas selective serotonin reuptake inhibitors are more tolerable but show inconsistent efficacy for IBS. If efficacious, serotonin-norepinephrine reuptake inhibitors like duloxetine would provide a useful alternative. We explored efficacy, tolerability, and time to onset of action of duloxetine in comorbid IBS-MDD in an open-label, 12-week trial. Repeated-measures mixed-effects regression analysis with the intent-to-treat sample assessed rate of change of the clinician-administered Gastrointestinal Symptoms Rating Scale, Montgomery-Åsberg Depression Rating Scale, and other clinician-administered and self-report scales. Seventeen Hispanic adults with current MDD and comorbid IBS meeting Rome III criteria entered the study. Medical and laboratory assessment ruled out alarm symptoms and signs inconsistent with IBS. Duloxetine led to significant improvement in Gastrointestinal Symptoms Rating Scale and Montgomery-Åsberg Depression Rating Scale scores and 71.4% and 64.3% intent-to-treat response rates for IBS and MDD, respectively. Abdominal pain severity decreased by 56%. Contrary to expectation of rapid analgesic effects, based on duloxetine studies for neuropathic pain, both IBS and MDD symptoms improved gradually; differences in slopes of improvement were nonsignificant. Duloxetine was moderately well tolerated at a mean endpoint dose of 60 mg/d. Study limitations include the lack of placebo control, modest sample size, single ethnic group, and high attrition rate. Duloxetine efficacy for comorbid IBS-MDD should be studied under placebo-controlled conditions with larger and more diverse samples.

Optimizing outcomes with alosetron hydrochloride in severe diarrhea-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder that causes a range of symptoms. Currently, alosetron hydrochloride (Lotronex®), a selective serotonin type 3 receptor antagonist, is the only medication approved for the treatment of severe diarrhea-predominant irritable bowel syndrome (IBS-D) in women who have inadequately responded to conventional therapy. Alosetron has demonstrated efficacy compared with placebo in clinical trials and has been shown to improve overall health-related quality of life (HRQoL). However, rare instances of ischemic colitis and severe complications of constipation have been reported. As a result, in 2000 alosetron was voluntarily withdrawn from the market but was reintroduced in 2002 with a more restricted indication and a requirement that clinicians and patients follow a prescribing program. Although the efficacy and benefit of alosetron has been clearly demonstrated, it has been used sparingly since its reintroduction. This brief review describes the history of alosetron, efficacy of alosetron in the treatment of IBS, the impact of severe IBS on HRQoL, safety considerations, the risk evaluation and mitigation strategy program under which alosetron is now prescribed, and an update on postmarketing surveillance data.

Use of probiotics in gastrointestinal disorders: what to recommend?

Perturbation of bacterial microflora of the gastrointestinal (GI) tract may play an important role in the pathophysiology of some GI disorders. Probiotics have been used as a treatment modality for over a century. They may restore normal bacterial microflora and effect the functioning of the GI tract by a variety of mechanisms. Probiotics are not currently regulated and only few randomized controlled trials exist investigating their efficacy in different GI disorders. They are available in a variety of formulations and delivery systems making interpretation and comparison of studies even more difficult. The efficacy of probiotics, either as a single strain or a combination of probiotics, has been tested in antibiotic-associated diarrhea, Clostridium difficile colitis, infectious diarrhea, ulcerative colitis, Crohn's disease, pouchitis, and irritable bowel syndrome, among other disorders. Results of the studies are reviewed in this article and recommendations for probiotic use in these disorders are made. Although probiotics appear to be generally safe in an outpatient setting, the situation may be different in immunocompromised, hospitalized patients who may be at a greater risk of developing probiotic sepsis. No studies exist addressing the issue of safety specifically. Many questions regarding use of probiotics in GI disorders remain to be answered in future studies, such as most optimal doses, duration of treatment, physiological and immunological effects, efficacy of specific probiotics in specific disease states, and safety in debilitated patients.

Developing valid and reliable health utilities in irritable bowel syndrome: results from the IBS PROOF Cohort.

OBJECTIVES: A "utility" is a measure of health-related quality of life (HRQOL) that ranges between 0 (death) and 1 (perfect health). Disease-targeted utilities are mandatory to conduct cost-utility analyses. Given the economic and healthcare burden of irritable bowel syndrome (IBS), cost-utility analyses will play an important role in guiding health economic decision-making. To inform future cost-utility analyses in IBS, we measured and validated the IBS utilities. METHODS: We analyzed data from Rome III IBS patients in the Patient Reported Observed Outcomes and Function (PROOF) Cohort-a longitudinal multi-center IBS registry. At entry, the patients completed a multi-attribute utility instrument (EuroQOL), bowel symptom items, IBS severity measurements (IBS Severity Scale (IBSSS), Functional Bowel Disease Severity Index (FBDSI)), HRQOL indexes (IBS quality-of-life instrument (IBS-QOL), Center for disease control-4 (CDC-4)), and the Worker Productivity Activity Index for IBS (WPAI). We repeated assessments at 3 months. RESULTS: There were 257 patients (79% women; age=43+/-15 years) at baseline and 85 at 3 months. The mean utilities in patients with severe vs. non-severe IBS were 0.70 and 0.80, respectively (P<0.001). There were no differences in utilities among IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed IBS (IBS-M) subgroups. EuroQOL utilities correlated with FBDSI (r=0.31; P<0.01), IBSSS (r=0.36; P<0.01), IBS-QOL (r=0.36; P<0.01), CDC-4 (r=0.44; P<0.01), WPAI presenteeism (r=0.16; P<0.01), abdominal pain (r=0.43; P<0.01), and distension (r=0.18; P=0.01). The utilities in patients reporting "considerable relief" of symptoms at 3 months vs. those without considerable relief were 0.78 and 0.73, respectively (P=0.02). CONCLUSIONS: EuroQOL utilities are valid and reliable in IBS. The utility of severe IBS (0.7) is similar to Class III congestive heart failure and rheumatoid arthritis. These validated utilities can be employed in future IBS cost-utility analyses.