Two different dose regimens of cisapride in the treatment of reflux oesophagitis: a double-blind comparison with ranitidine

We conducted a double-blind study comparing two dosage regimens of a prokinetic drug, cisapride (10 mg q.d.s. and 20 mg b.d.), with a low dose of a H₂ receptor antagonist (150 mg ranitidine b.d.) in the treatment of 155 patients with reflux oesophagitis as determined by endoscopy. The active treatment took 8 to 12 weeks depending on whether complete healing was found at endoscopy. Improvement in oesophagitis grades from baseline to endpoint was observed in 68% of patients in the 10 mg cisapride q.d.s. group, 83 % in the cisapride 20 mg b.d. group and 81% in the ranitidine group (N.S.). At endpoint, the percentages of endoscopically cured patients with initial grades I or II were 52% for 10 mg cisapride q.d.s., 71% for 20 mg cisapride b.d. and 80% for ranitidine (N.S.). The proportional improvement of the overall reflux symptom score (60%) also showed no significant difference between the three groups. In the treatment of mild reflux oesophagitis (grades I and II) similar results can be expected from 20 mg cisapride b.d. and 150 mg ranitidine b.d. As the results of the two dosage regimens of cisapride were not different, the 20 mg twice daily regimen is preferred because it will improve patient compliance. It is concluded that in reflux oesophagitis grades I and II, the efficacy of 20 mg cisapride b.d. and 150 mg ranitidine b.d. are broadly similar.     

Acute treatment of reflux oesophagitis: a multicentre study to compare 150 mg ranitidine twice daily with 300 mg ranitidine at bedtime

A randomized, double-blind, clinical trial was undertaken to compare 150 mg ranitidine b.d. with 300 mg ranitidine nocte in the treatment of reflux oesophagitis. Endoscopy data were evaluable for 336 patients after 8 weeks of treatment. At this time 75% of patients who received 150 mg ranitidine b.d., and 73% of those who received 300 mg nocte, had healed or showed endoscopic improvement to grade I oesophagitis. At 12 weeks these rates had increased to 89 and 88%, respectively. Oesophageal biopsies from 258 patients at 8 weeks showed histological improvement in 44 and 47% of those treated with 150 mg ranitidine b.d. and 300 mg ranitidine nocte, respectively. After 12 weeks histological improvement was apparent in 57 and 54% of biopsies from each group, respectively. Symptom severity and frequency was reduced to a similar extent by both treatments. Adverse events were reported by 15 patients. A 300-mg bedtime dose of ranitidine was found to be a well-tolerated, effective alternative to twice daily treatment in reflux oesophagitis.     

Omeprazole or ranitidine plus metoclopramide for patients with severe erosive oesophagitis. A cost-effectiveness analysis

The objective of this study was to evaluate the clinical and economic effects of 2 clinical strategies for treating severe (grade II and above) erosive oesophagitis or poorly responsive gastro-oesophageal reflux disease. A single-blind, randomised controlled trial of up to 8 weeks' duration was undertaken comparing omeprazole with ranitidine plus metoclopramide in patients with severe and symptomatic erosive oesophagitis (endoscopic grade II and above). Two cost-effectiveness ratios were calculated: cost per healed patient and cost per symptom-free day. The study perspective was that of the payer or insurer of medical care. Healing rates were significantly higher among omeprazole-treated patients than among those who received ranitidine/metoclopramide at 4 weeks (68.5% vs 30.4%; p < 0.01) and overall (81.5% vs 45.7%; p < 0.01). Overall, mean gastrointestinal-related direct medical costs per healed patient were lower for the omeprazole group ($US189.60) than for the ranitidine/metoclopramide group ($US319.28). The incremental cost of an additional cure with omeprazole compared with ranitidine/metoclopramide was $US24.05. The overall average cost per symptom-free day was lower in the omeprazole group ($US7.88) than in the ranitidine/metoclopramide group ($US10.81). The incremental cost to obtain an additional symptom-free day with omeprazole, compared with ranitidine/metoclopramide, was $US1.41. In conclusion, superior efficacy at comparable cost is achieved by omeprazole compared with ranitidine/metoclopramide in the treatment of patients with severe erosive oesophagitis.     

Rapid dose escalation with quetiapine: a pilot study

The original dosing recommendations for quetiapine in the treatment of schizophrenia suggested escalation to 400 mg/d using the following schedule, administered twice daily in divided doses: Day 1, 50 mg; Day 2, 100 mg; Day 3, 200 mg; Day 4, 300 mg; Day 5, 400 mg. In practice, however, clinicians often exceed these recommendations because of the need to obtain a therapeutic response in patients with psychosis as quickly as possible. This study was designed to determine a faster tolerable dosage-escalation schedule for quetiapine in acutely ill, hospitalized patients with schizophrenia. In this multicenter, placebo-controlled, double-blind pilot study, adult patients were randomly assigned to escalation schedules that would achieve a target dosage of 400 mg/d in either 5, 3, or 2 days. Safety and tolerability were assessed by interviews, physical examinations and vital signs, laboratory tests, and electrocardiograms. The enrolled population consisted of 69 patients who were randomized to 1 of the 3 dose-escalation schedules. Treatment-related adverse events were few among the 67 evaluable patients, with most rated as mild in intensity. Among 69 enrolled patients, only 3 withdrew because of an adverse event (agitation). Objective assessments and adverse events were similar between the 3 groups. In this study of patients with acute schizophrenia, quetiapine dosage was increased to 400 mg/d in 5, 3, and 2 days with similar safety and tolerability, suggesting that escalation to therapeutically effective dosages can be accomplished in less than 5 days.     

Pharmacokinetics and pharmacodynamics of famotidine in patients with reflux oesophagitis

Summary The pharmacokinetics, pharmacodynamic effect and clinical efficacy of famotidine were studied in 10 patients with reflux oesophagitis Grades I and II. For the pharmacokinetic studies the patients received 20 mg famotidine i. v.The half-life of famotidine was 3.8 h, the total plasma clearance was 297 ml·min^–1, and a steady state volume of distribution of 1.21·kg^–1 was found. For pharmacodynamic assessment, intraoesophageal pH-metry was performed without and after acute treatment with famotidine 20 mg i. v. and following 3 weeks of oral famotidine 80 mg b. d. The resultant percentage total acid exposure time (pH<4 within 24 h) were 23.9%, 19.0% and 19.2% (median), respectively (NS). At the end of 6 weeks of oral therapy, symptomatic and endoscopic improvement had occurred in 9 and 5 patients, respectively.Our study shows that the pharmacokinetics of famotidine in patients with reflux oesophagitis is comparable to that in healthy volunteers and peptic ulcer patients. The clinical response to the treatment appeared comparable to that found after other H₂-receptor antagonists.     

Lansoprazole versus ranitidine in the maintenance treatment of reflux oesophagitis

Aims: To assess the relative efficacies of lansoprazole 15 mg once daily, lansoprazole 30 mg once daily and ranitidine 300 mg b.d. in the maintenance treatment of reflux oesophagitis for 12 months. Methods: Multicentre, out-patient, double-blind, parallel group, prospectively randomized clinical trial. Patients with grade 0, asymptomatic oesophagitis after 8 weeks of treatment with lansoprazole 30 mg once daily were randomized to receive lansoprazole 30 mg once daily (L30) (n=75), lansoprazole 15 mg once daily (L15) (n=86) or ranitidine 300 mg b.d. (R600) (n=74) for 12 months. Endoscopy was repeated at 6 and 12 months, and symptomatic assessment was made every 3 months. Efficacy was primarily assessed by the time to endoscopically confirmed relapse (oesophagitis grade1) and the proportion of patients who relapsed during the 12-month study period. Severity of symptoms were secondary efficacy measures. Results: For all patients randomized with at least one post-baseline endoscopy (intent-to-treat principle) both lansoprazole 15 mg (P<0.001) and lansoprazole 30 mg (P<0.001) were significantly superior to ranitidine 600 mg with respect to time to endoscopic relapse. There was no difference between the lansoprazole groups (P=0.11). There was evidence of relapse in 27 of 86 (31.4%), 15 of 75 (20.0%) and 50 of 74 (67.6%) of the patients treated with lansoprazole 15 mg and 30 mg and ranitidine 600 mg, respectively. Patients receiving treatment with either lansoprazole dosages experienced significantly less severe heartburn and regurgitation than those patients treated with ranitidine. There were no differences between the treatment groups with respect to the severity or incidence of adverse events. No clinically significant laboratory changes were observed in any of the treatment groups. Serum gastrin levels were elevated in all treatment groups, and most markedly in those patients receiving lansoprazole, but there was no significant difference between the treatments. Morphological and immunohistochemical examination of the gastric biopsies revealed no clinically relevant changes from baseline in any of the treatment groups. Conclusion: Both lansoprazole 15 mg and lansoprazole 30 mg once daily are significantly more effective than high-dose ranitidine in maintaining reflux oesophagitis in remission.     

A comparative study of cisapride and ranitidine at controlling oesophageal acid exposure in erosive oesophagitis

Background: The severity of gastro-oesophageal reflux disease is generally considered to be related to the extent of oesophageal acid exposure. Current therapies include antisecretory and prokinetic agents. We compared two of these, ranitidine and cisapride, in their ability to lower oesophageal acid exposure in patients with erosive oesophagitis. Methods: Seven patients with Savary–Miller's grade II–IV oesophagitis and with oesophageal contact time ± 8% were studied. Mean lower oesophageal sphincter pressure was 4.6 mmHg. Oesophageal acid contact time was 25.6 ± 5.6%. Each patient received ranitidine 150 mg b.d., ranitidine 150 mg q.d.s., or cisapride 10 mg q.d.s. in a randomized 3-way cross-over design. Intra-oesophageal pH was monitored during 24 h for each of these treatments in a controlled hospital environment, while consuming a high fat, high calorie diet. Results: Cisapride and ranitidine at both doses decreased the acid contact time and the number of reflux episodes. However, a minority of patients treated with ranitidine, and none with cisapride, diminished their oesophageal acid contact time to a normal value of < 5%. No treatment significantly decreased nocturnal acid exposure. Conclusion: In patients with severe gastro-oesophageal reflux disease both cisapride and ranitidine demonstrably lower oesophageal acid exposure, but neither therapy predictably normalizes it.     

A single night-time dose of famotidine is equivalent to ranitidine in decreasing 24-hour gastric acidity in asymptomatic duodenal ulcer subjects

Six asymptomatic, non-smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8-15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed-time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.     

Increase of oral methadone dose in methadone injecting patients: a pilot study

A pilot study was initiated in seven methadone injecting patients to examine whether intravenous methadone use in patients in oral methadone maintenance treatment could be decreased by increased oral methadone dose. During the study, patients had a standardized methadone dose increase for three weeks, followed by a 12-week follow-up period. Mean methadone doses prior to, and at the end of the study, were 99 mg/day and 163 mg/day, respectively. On week 15, the mean frequency of injection and the mean proportion of methadone dose injected were reduced to 46% of the values measured at week 0 (p = 0.043 and p = 0.028, respectively). Two patients did not modify their fre- quency, nor their dose of injected methadone, four patients decreased their use of injectable methadone, while one completely stopped injecting methadone. Since the completion of the pilot study, an augmentation of oral methadone dose has been proposed as a therapeutic option to 18 other methadone injecting patients. Five patients did not change their frequency of injection. They did, however, either completely stop or decrease their illicit opiate consumption. Nine patients decreased their frequency of methadone injection from a mean 95% down to 35%. Finally, four patients completely stopped injecting methadone. Although the present results have to be confirmed by controlled studies including a larger number of patients, when considering the high frequency of methadone injection in some places and the associated problems, the therapeutic option of increasing methadone dose should be considered further.     

Comparison of ranitidine, domperidone maleate and ranitidine + domperidone maleate in the short-term treatment of reflux oesophagitis

In the treatment of reflux oesophagitis, either drugs preventing regurgitation of gastric juice in the lower oesophagus or pharmacological agents increasing the pH of the refluxing material are employed. In the present study 45 outpatients with reflux oesophagitis were randomly treated with either ranitidine (150 mg b.i.d.) or domperidone maleate (20 mg t.i.d.) or both drugs for six weeks. Before and after treatment the severity of dyspeptic symptoms and the grade of endoscopic and histological changes were assessed. The three therapeutic regimens were significantly and equally effective in inducing symptomatic relief and promoting endoscopic and histological disappearance or improvement of oesophagitis. The combined use of ranitidine and domperidone maleate failed to show any additional benefit compared with treatment with either drug alone.     

A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis

Background: Lansoprazole is a new proton pump inhibitor which produces prolonged decrease of gastric acidity. The aim of this study was to compare lansoprazole to a standard dose of ranitidine in the treatment of patients with reflux oesophagitis. Methods: Two hundred and forty-seven patients with erosive oesophagitis were randomly assigned to 8 weeks of treatment with either 30 mg lansoprazole once daily or 150 mg ranitidine twice daily. Results: Two hundred and forty-two patients were included in the analysis. Lansoprazole (30 mg) daily, healed oesophagitis in 92.1% of patients after 8 weeks of treatment. This was significantly superior to 150 mg ranitidine b.d.s. which healed oesophagitis in 69.9% of patients (P < 0.001). Relief of reflux symptoms was superior with lansoprazole to that with ranitidine. Both lansoprazole and ranitidine were well tolerated with no serious drug-related adverse events noted. Conclusion: Lansoprazole, 30 mg once daily, is highly effective and safe in the short-term treatment of erosive oesophagitis.     

Treatment resistant smokers: a pilot study of nicotine nasal spray and inhaler

A growing proportion of smokers are those who have failed prior treatments for cessation. We tested the efficacy of nicotine nasal spray and nicotine inhaler in two uncontrolled, open-label studies of 19 and 20 smokers who had previously failed nicotine patch therapy. As in the three prior studies of treatment failures, 6 month abstinence rates were extremely low both with the nasal spray (0%) and the inhaler (5%). We discuss possible treatments for and methodological issues in researching treatment-resistant smokers.     

The effect of famotidine addition on olanzapine-induced weight gain in first-episode schizophrenia patients: a double-blind placebo-controlled pilot study.

Olanzapine treatment is associated with substantial weight gain. In this double-blind placebo-controlled study we evaluated whether the H2 antagonist famotidine may prevent/attenuate olanzapine-induced weight gain. Fourteen first-episode DSM-IV schizophrenia patients were randomly allocated to receive either famotidine (40 mg/day, n=7) or placebo (n=7) in addition to olanzapine (10 mg/day) for 6 weeks. All patients completed the trial. Patients in both groups showed a similar increase in body weight (olanzapine/famotidine: 4.8 (3.2) kg and olanzapine/placebo: 4.9 (1.6) kg, respectively; a between-group difference of 0.14 (1.3) kg). Four of seven (57.1%) patients in the olanzapine/famotidine group and three of seven (42.9%) in the olanzapine/placebo group gained at least 7% of their initial body weight, a cut-off for clinically significant weight gain. Famotidine addition was safe and well tolerated and did not interfere with olanzapine's therapeutic effect. In conclusion, famotidine (40 mg/day for 6 weeks) is not effective in preventing/attenuating weight gain in olanzapine-treated first-episode schizophrenia patients.     

Rebound hypersecretion after H2-antagonist withdrawal—a comparative study with nizatidine, ranitidine and famotidine

Our previous study demonstrated rebound nocturnal acid hypersecretion after a 4-week course of nizatidine. Nocturnal acid output was increased by 77% two days after discontinuing treatment compared with pretreatment values. To confirm this effect with other H2-blockers we assessed daytime intragastric pH, fasting and meal-stimulated plasma gastrin and nocturnal acid output in 9 duodenal ulcer patients in remission before, during and two days after treatment with three different drugs. Each patient received 4-week courses of 300 mg ranitidine, 40 mg famotidine or 300 mg nizatidine, taken at 20.00 hours in randomized order with a 'washout' period of 4 weeks between each course of drug. Median nocturnal acid output (mmol/10 h) decreased during treatment with ranitidine to 3 (range 0-17), famotidine to 4 (1-12) and nizatidine 6 (0-40) compared with the respective pre-treatment values, 49 (20-126; P less than 0.01), 52 (22-105; P less than 0.01) and 32 (23-114; P less than 0.01). Two days after discontinuing treatment nocturnal acid output was increased after ranitidine at 77 (28-237; P less than 0.04) and after nizatidine at 64 (17-130; P less than 0.05) compared with pre-treatment values. There was no significant change in nocturnal acid output after famotidine at 57 (27-107) compared with the pre-treatment value. There was no change in daytime intragastric pH with any drug during or after treatment compared with the pre-treatment values. Fasting and meal-stimulated plasma gastrin concentrations were increased on the final treatment day with ranitidine and famotidine but had returned to pretreatment levels two days after treatment. The rebound acid hypersecretion may contribute to the high ulcer relapse rate after discontinuation of H2-receptor antagonists.     

Omeprazole is superior to ranitidine plus metoclopramide in the short-term treatment of erosive oesophagitis

Histamine H₂-receptor antagonists are moderately effective in symptomatic treatment and healing of erosive oesophagitis, but they are not as effective as the proton pump inhibitor omeprazole. In some studies prokinetic agents seem to increase the effectiveness of H₂-antagonists, but no study comparing the efficacy of omeprazole to H₂-antagonists plus prokinetic agents has been performed. The purpose of this study was to compare the efficacy and tolerability of 20 mg omeprazole daily with 150 mg ranitidine b.d.s. plus the prokinetic agent 10 mg metoclopramide q.d.s. in patients with erosive oesophagitis. After both 4 and 8 weeks of treatment, omeprazole healed the mucosa in significantly more patients than did ranitidine plus metoclopramide. Omeprazole also provided significantly greater relief from daytime heartburn, nighttime heartburn, and acid regurgitation, and was associated with decreased concomitant antacid use. Although the overall incidence of adverse events was similar in the two treatment groups, a significantly higher number of treatment-related adverse events and more treatment-related withdrawals from the study occurred in the ranitidine plus metoclopramide treatment group. Omeprazole is more effective and better tolerated than the combination of standard dose ranitidine plus metoclopramide for patients with erosive oesophagitis.     

Ranitidine for erosive oesophagitis: a double-blind, placebo-controlled study

A multicentre, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of ranitidine 150 mg and 300 mg in 342 patients with erosive oesophagitis. Treatment was given four times daily, and continued for 12 weeks or until healing (that is, normal or only erythematous mucosa). Erosive oesophagitis healing rates, as determined by endoscopy, were significantly greater in ranitidine-treated patients by 4 weeks compared with those of placebo-treated patients. By 12 weeks, erosive oesophagitis healing rates were 83 and 81% for ranitidine-treated patients (150 and 300 mg, respectively) and 58% for placebo-treated patients (P less than or equal to 0.001, ranitidine vs. placebo). Symptomatic relief was achieved within 24 hours after starting either dosage of ranitidine. Heartburn frequency (P less than 0.001) and severity (P less than 0.001), as well as antacid consumed per week (P less than 0.001), were reduced in both ranitidine groups in comparison with placebo. Healing rates and symptom relief were similar in the two ranitidine groups. Both dosages of ranitidine were well tolerated. Ranitidine (150 mg) given four times daily appears to be as effective as 300 mg ranitidine given four times daily in patients with moderate to severe oesophageal erosions.     

Daytime acid secretion after a single dose of ranitidine and cimetidine — a double blind crossover study

Summary The purpose of the study was to evaluate the duration of inhibition of acid secretion by single oral doses of cimetidine and ranitidine. Basal and postprandial acid secretion in 6 healthy volunteers were measured for 14 h by intermittent aspiration and prolonged intragastric titration. 400 mg cimetidine reduced daytime acid secretion by 22% and 150 mg ranitidine produced 38% inhibition. Although the elimination half lives of the drugs were similar, ranitidine led to more pronounced inhibition of acid secretion during the later part of the day. The longer duration of pronounced acid inhibition by ranitidine appears to be due solely to its greater potency.