Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety

Summary

Background

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion.

Aim

To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.

Methods

A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked.

Results

Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea.

Conclusions

Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

     

Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms

Background:

In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose.

Aim:

To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms.

Methods:

After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded.

Results:

The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0–12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopra- mide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found.

Conclusions:

In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.

     

The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro-oesophageal reflux disease

Background:

Mosapride is a novel prokinetic agent facilitating acetylcholine release from the enteric cholinergic neurones through a selective 5-HT₄ receptor agonistic action. It is also active through its main metabolite M1, which is a 5-HT₃ antagonist. The importance of motor dysfunction in the pathogenesis of gastro-oesophageal reflux disease (GERD) makes it interesting to examine the effect of mosapride on oesophageal acid exposure.

Methods:

The effect of mosapride on oesophageal 24-h acid reflux variables was studied in 21 patients with GERD symptoms and a pre-entry total acid exposure time (pH < 4) of more than 5%. Ambulatory pH monitoring was performed after treatment with 40 mg mosapride citrate or placebo q.d.s. for 2 days in random order, using a double-blind crossover technique, with a washout period of at least 5 days.

Results:

Mosapride was significantly more effective than placebo in decreasing the total number of reflux episodes, the total number of reflux episodes lasting more than 5 min and the total time, as well as the amount of day time, of intra-oesophageal pH below 4. Consequently, mosapride also significantly improved total acid clearance time.

Conclusion:

Mosapride 40 mg q.d.s. is effective in decreasing acid reflux in the oesophagus in patients with GERD and therefore has the potential to be effective in the treatment of this disease.

     

Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study

Summary

Background

Although laxatives are a first‐line treatment for constipation, there are few randomized placebo‐controlled trials assessing their efficacy.

Aim

To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation.

Methods

55 patients (age 19–89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3‐day run‐in period. Patients recorded stool frequency and consistency and adverse events.

Results

In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl‐treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P = 0.0061). Mean stool consistency score improved from ‘hard’ (run‐in) to between ‘soft’ and ‘well‐formed’ during bisacodyl treatment, remaining between ‘moderately hard’ and ‘hard’ for placebo treatment (P < 0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups.

Conclusions

Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.

     

The effects of low doses of ranitidine on intragastric acidity in healthy men

Background:

H₂-receptor antagonists are becoming widely available as over-the-counter medications for the treatment of heartburn and excess gastric acidity.

Aim:

To determine the effects of single low doses of ranitidine on intragastric acidity.

Methods:

Intragastric pH was measured for 9 h after lunch in five studies involving 24 healthy male volunteers. Antacid was given to all subjects on day 1. They then received single oral doses of a study drug 45 min after lunch on four separate occasions: placebo and either ranitidine 25 mg, 75 mg or 125 mg were given double-blind according to a predetermined randomization schedule.

Results:

During both of the post-dosing time periods (0–5 h and 5–9 h) there were significant decreases in integrated intragastric acidity for each ranitidine dose compared with placebo (P < 0.0001). There was a significant linear relationship between dose and integrated intragastric acidity with a greater decrease in acidity with increasing ranitidine doses (P < 0.0001). Compared with placebo, time with pH > 3 was significantly greater for ranitidine 75 mg and 125 mg (P < 0.001), but not ranitidine 25 mg. Results with the antacid were similar to placebo.

Conclusions:

Using low doses of ranitidine (25, 75 or 125 mg) there was a dose-related decrease in intragastric acidity for 9 h after dosing. A single dose of antacid did not decrease intragastric acidity significantly.

     

One-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori

Background:

One-week triple therapies have been endorsed as the treatment regimens of choice for eradication of Helicobacter pylori infection. Those that include clarithromycin appear to be the most effective.

Aim:

To review reports of triple therapies that include clarithromycin.

Methods:

Reports were identified from the literature to May 1998. The variation between study designs prevents a formal meta-analysis. A measure of the relative efficacies of regimens has, however, been gained by comparison and by pooling of intention-to-treat eradication rates.

Results:

One hundred and ninety-two studies were identified which included 264 treatment arms of a 1-week triple therapy composed of clarithromycin with amoxycillin or a nitroimidazole (metronidazole or tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor (omeprazole, lansoprazole or pantoprazole). From reports of these studies, an intention-to-treat H. pylori eradication rate could be determined from 210 treatment arms of 151 studies.

Conclusions:

There is little to choose between the efficacies of 1-week clarithromycin-based triple therapy eradication regimens. However, those comprising clarithromycin, a nitroimidazole and either ranitidine bismuth citrate or a high dose of omeprazole are, in general, the most effective. Against antibiotic-resistant strains of H. pylori, regimens including ranitidine bismuth citrate may be more effective than those including a proton pump inhibitor.

     

Delta-9-tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study

Background:

Delta-9-tetrahydrocannabinol (THC), the active constituent of marijuana, is an effective agent in the prevention of chemotherapy-induced nausea and vomiting.

Aim:

To determine the effect of THC on gastric emptying of a radiolabelled solid food in humans.

Methods:

Thirteen healthy volunteers underwent gastric emptying studies after receiving THC and placebo in a randomized double-blind fashion on 2 separate days. THC, at a dose of 10 mg/m² of body surface area, or placebo were administered.

Results:

Gastric emptying after THC was slower than placebo in all subjects. Mean percentage of isotope remaining in the stomach was significantly greater than after placebo from 30 min (85.5 ± 4.3% vs. 94.2 ± 1.4% placebo and THC, respectively, P < 0.05) to 120 min (45.6 ± 7.2% vs. 73.9 ± 7.1% placebo and THC, respectively, P < 0.001) after the test meal. No correlation was found between plasma THC levels and the delay in gastric emptying.

Conclusions:

THC at a dose used for preventing chemotherapy-induced nausea and vomiting significantly delays gastric emptying of solid food in humans. Therefore, the anti-emetic property of THC may be mediated through the central nervous system.

     

Effects of cholinergic agents on anorectal physiology

Background:

Despite their potential therapeutic benefit, the effects of cholinergic agents on anal function have been poorly investigated.

Aim:

To analyse the effects of neostigmine and atropine on anorectal responses to rectal isobaric distension.

Methods:

This was a placebo-controlled, randomized, double-blind crossover study, performed in 12 healthy volunteers who received intravenously, on 3 separate days, neostigmine, atropine or the placebo. During each day of the experiment, seven pressure steps (ranging from 1 to 31 mmHg) in three different protocols of rectal isobaric distension (phasic, stepwise and tonic) were applied using an electronic barostat. Manometric responses of the anal canal, adaptative volumes and perception scores of the rectum were recorded.

Results:

During stepwise distension, a significant drug effect was encountered at the anal level. No drug effect was observed on the other investigated parameters (rectal volumes and rectal perception scores) or for the other modes of distension. Compared to placebo, neostigmine significantly decreased pressures at the upper level of the anal canal for both recto anal inhibitory reflex and mean resting pressures. In contrast, atropine significantly increased pressures at the lower part of the anal canal but did not modify upper anal pressures.

Conclusion:

The present study suggests that cholinergic effects result more from an indirect action on intermediate neurotransmitters and rectal myenteric neurons, than from a direct action on anal targets.

     

Estimating the cost of lost productivity in dyspepsia

Background:

In the field of gastrointestinal disease, productivity costs are highly relevant because work loss is substantial in dyspeptic patients. Productivity costs are normally calculated by multiplying days absent valued by gross earnings. This, however, might lead to an overestimation.

Aim:

To use a conservative approach to calculating productivity costs, taking absence compensating mechanisms into account.

Methods:

Patients who visited their general practitioner for the first time with dyspeptic complaints and patients who were known to have persistent dyspeptic complaints were enrolled in two studies. In total, 136 patients completed a questionnaire about their employment situation, absence from work and absence compensating mechanisms.

Results:

Sixty-six of the respondents had a paid job, of which 25 (38%) reported absence from work during the previous 4 weeks (average 3.0 days, 1.9 days related to dyspeptic complaints). More than 50% of the employed respondents answered that absence could be compensated for by colleagues, and only in 8% of the cases was absence compensated for by overtime. Using our conservative approach, only one-quarter of the productivity costs remained, compared to the current approach of valuing each day absent as a loss of productivity.

Conclusions:

We suggest using both the current and the conservative approaches, analogous to the principles of sensitivity analysis, to avoid overestimation of productivity costs.

     

Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine

Background:

Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (⁷⁵Selenium HomotauroCholic Acid Test) can accurately diagnose this condition.

Aim:

To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine.

Method:

Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed.

Results:

Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3–12.6). Their median daily faecal weight was 285 g (range 85–676) and median faecal fat output was 17 mmol/24 h (range 8.3–38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea.

Conclusions:

Idiopathic bile acid malabsorption, once suspected, especially by documenting true ‘large volume’ watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.

     

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions

Summary

Background

Zollinger–Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long‐term maintenance.

Aims

The safety and efficacy data for short‐term (6‐month) treatment of Zollinger–Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years.

Methods

The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid‐reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h.

Results

Twenty‐four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90–100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported.

Conclusions

Maintenance oral pantoprazole therapy up to 3 years at dosages of 40–120 mg b.d. was effective and well tolerated in patients with Zollinger–Ellison syndrome and other hypersecretory conditions.

     

Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies)

Background:

The efficacy of H₂-receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown.

Aim:

To evaluate the efficacy of proton pump inhibitor therapy in functional dyspepsia.

Methods:

Patients (n = 1262) with a clinical diagnosis of functional dyspepsia (persistent or recurrent epigastric pain or discomfort for at least 1 month and a normal upper gastrointestinal endoscopy) were randomized to receive omeprazole 20 mg, 10 mg or identical placebo, for 4 weeks. Symptoms were assessed using validated measures. Helicobacter pylori status was determined pre-entry by a ¹³C-urea breath test.

Results:

On an intention-to-treat analysis (n=1248), complete symptom relief was observed in 38% on omeprazole 20 mg, compared with 36% on omeprazole 10 mg and 28% on placebo (P = 0.002 and 0.02, respectively). Among those with ulcer-like and reflux-like dyspepsia, complete symptom relief was achieved in 40% and 54% on omeprazole 20 mg, and 35% and 45% on omeprazole 10 mg, respectively, compared with 27% and 23% on placebo (all P < 0.05, except omeprazole 10 mg in ulcer-like dyspepsia, P = 0.08). There was no significant benefit of omeprazole over placebo in dysmotility-like dyspepsia. Symptom relief was similar in H. pylori-positive and negative cases.

Conclusions:

Omeprazole is modestly superior to placebo in functional dyspepsia at standard (20 mg) and low doses (10 mg) but not in patients with dysmotility-like dyspepsia.

     

Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study

Background:

It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low-dose theophylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood flow and sodium excretion in cirrhotic patients.

Methods:

Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy.

Results:

After 7 days of spironolactone there were increases in urinary sodium excretion (43.5 ± 15.6 vs. 106.8 ± 34.7 mmol/day; P < 0.05) and urine volume (769.1 ± 206.5 vs. 1541.6 ± 342.6 mL/day; P < 0.05). No changes in the patients’ weight, creatinine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy.

Conclusion:

Adenosine antagonism in the form of low-dose theophylline is less efficacious than spironolactone in the management of cirrhotic ascites.

     

Interdigestive antroduodenal motility and gastric acid secretion

Background:

In humans, interdigestive acid secretion and antroduodenal motility are closely related with cyclic variations in acid secretion, synchronous with the various phases of the migrating motor complex (MMC). Duodenal acidification inhibits antral motility, but little is known about the effect of acute acid inhibition on antroduodenal motility.

Aim:

To study the effect of acute acid inhibition on antroduodenal motility.

Subjects:

Ten healthy volunteers (four men and six women; age range 20–31 years).

Methods:

Antroduodenal motility (perfusion manometry) and gastric acid secretion (continuous aspiration with recovery marker) were measured simultaneously. Each subject was studied twice in random order during (1) intravenous infusion of saline for one–two complete MMC cycles and (2) during acute acid inhibition with intravenous famotidine (bolus 20 mg, continuous infusion 4 mg/h) for one–two complete MMC cycles or at least 240 min.

Results:

In the saline study, acid output in phase III (2.1 ± 0.3 mmol/10 min) and late phase II (1.7 ± 0.2 mmol/10 min) was significantly (P < 0.05) increased over early phase II and phase I (1.2 ± 0.2 and 1.2 ± 0.2 mmol/10 min, respectively). Famotidine increased gastric pH to above pH 6 within 30 min. After acid inhibition, duration of MMC cycle during famotidine (106 ± 8 min) was not significantly different from the saline experiment (133 ± 14 min). Phase distribution of the MMC cycle was not significantly different between famotidine (I, II and III: 12 ± 3, 82 ± 3 and 5 ± 1%) and saline (I, II and III: 13 ± 3, 83 ± 3 and 4 ± 1%).

Conclusions:

Gastric acid secretion varies cyclically with interdigestive antroduodenal motility. Acute acid inhibition with intravenous famotidine does not significantly affect interdigestive antroduodenal motility.

     

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection

Background

We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection.

Methods

From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days; or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary.

Results

Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects.

Conclusions

With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

     

Variation in taste of topical lignocaine anaesthesia for gastroscopy

Aim:

To study the distribution and determinants of taste variation for lignocaine spray (Xylocaine; Astra Pharmaceuticals, King’s Langley, UK).

Methods:

Sixty-nine patients (male:female 49:20, mean age 48.5 years) attending for open access upper gastrointestinal endoscopy were studied. Taste perceived after applying 4 doses (40 mg) of lignocaine spray to the oro-pharynx was recorded prior to endoscopy.

Results:

37/69 (54%, 95% CI: 41–66%) perceived the taste of the lignocaine spray as bitter, whilst 24/69 (35%, 95% CI: 24–47%) and 6/69 (9%, 95% CI: 3–18%) perceived the taste as either fruity/sweet or tasteless. The variation in taste did not correlate with either demographic features or H. pylori infection, but duodenal ulceration was slightly more common amongst bitter tasters.

Conclusion:

The taste of lignocaine is not uniform, but the basis of this variability is uncertain.

     

The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the rat

Background:

Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results.

Aim:

To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol.

Methods:

Four groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4.

Results:

TNBS-induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin-treated animals was of borderline significance.

Conclusions:

Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti-inflammatory action.

     

Effects of tablet and effervescent formulations of ranitidine 75 mg and cimetidine 200 mg on gastric acidity and oesophageal acid exposure in healthy humans

Background:

Because of their tolerance and safety, low doses of H₂-receptor antagonists are now increasingly used in some countries for self-care medication of gastro-oesophageal reflux symptoms.

Aim:

The purpose of this randomized, double-blind, placebo-controlled, five-way crossover study was to determine and to compare the effects of low doses of ranitidine and cimetidine both on gastric pH and on oesophageal acid exposure.

Methods:

Gastric and oesophageal pH were simultaneously monitored in 20 healthy subjects using two glass pH electrodes, after placebo and single doses of ranitidine 75 mg and cimetidine 200 mg (effervescent and tablet forms), for 4 h before and after a meal.

Results:

During the fasting period, median gastric pH rose significantly with both drugs, but more rapidly with the effervescent forms; the oesophageal acid exposure was significantly decreased by all drug regimens. After the meal, although there was no significant difference in gastric pH values, oesophageal acid exposure was significantly decreased in comparison with placebo with both forms of ranitidine (P < 0.05), and also for ranitidine tablets in comparison with cimetidine tablets (P < 0.05).

Conclusions:

Low doses of ranitidine and cimetidine increase gastric pH, with a more pronounced effect for ranitidine. Effervescent formulations of both drugs induce a slightly more rapid initial increase in pH than tablets. Ranitidine demonstrates a more prolonged effect than cimetidine and decreases oesophageal acid exposure monitored after a meal ingested 4 h after the drug intake.

     

Psyllium is superior to docusate sodium for treatment of chronic constipation

Background:

Stool softening is a physician’s first step in the management of chronic constipation.

Aim:

To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium.

Methods:

The multi-site, randomized, double-blind, parallel-design study of 170 subjects with chronic idiopathic constipation involved a 2-week baseline (placebo) phase followed by 2 weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Stools were collected and assessed.

Results:

Compared to baseline, psyllium increased stool water content vs. docusate (psyllium 2.33% vs. docusate 0.01%, P = 0.007). Psyllium also increased stool water weight (psyllium 84.0 g/BM; docusate 71.4 g/BM; P = 0.04), total stool output (psyllium 359.9 g/week; docusate 271.9 g/week; P = 0.005), and O’Brien rank-type score combining objective measures of constipation (psyllium 475.1; docusate 403.9; P = 0.002). Bowel movement (BM) frequency was significantly greater for psyllium (3.5 BM/week) vs. docusate (2.9 BM/week) in treatment week 2 (P = 0.02), with no significant difference (P > 0.05) between treatment groups in treatment week 1 (3.3 vs. 3.1 BM/week).

Conclusion:

Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation.