Summary
Gastro-oesophageal reflux disease (GORD) ranges from episodic symptomatic reflux without oesophagitis to severe oesophageal mucosal damage, such as Barrett’s metaplasia or peptic stricture. The multifactorial pathogenesis of GORD prevents medical cure of the disease. GORD is a chronic disease with a high tendency to relapse, requiring a long term treatment strategy in practically all patients. Complete healing of all mucosal lesions is not necessarily the aim of treatment in all patients. In milder forms of reflux disease, symptom relief is the most important goal.
Many patients with mild GORD do well on symptomatic self-care with antacids and/or alginate. In addition, lifestyle changes should be advised to all patients: these improve symptoms and enhance the efficacy of therapy.
In the acute treatment of GORD the prokinetic drug cisapride has been shown to be effective in relieving symptoms and healing grade I to II oesophagitis. Cisapride decreases symptomatic and endoscopic relapse in patients with mild GORD.
Histamine H2-receptor antagonists are effective in relieving reflux symptoms in about 50% of patients, but with regard to healing, H2-antagonists appear to be mainly effective in grades I and II and not in higher grades of oesophagitis. Maintenance treatment with H2-antagonists is mainly symptomatically effective in patients with mild GORD.
Proton pump inhibitors (PPIs) provide significantly higher healing rates of reflux oesophagitis than H2-antagonists, even in the more severe cases of oesophagitis and Barrett’s ulcers. PPIs are also effective in patients with oesophagitis refractory to treatment with H2-antagonists. PPIs have become the drugs of first choice in healing of all patients with more severe forms of reflux oesophagitis, and increasingly also for patients with milder forms of oesophagitis, certainly those who fail to respond to other drugs. In maintenance treatment of GORD, PPIs are the most effective drugs, offering the possibility of keeping nearly all patients in remission with adjusted doses. Current patient data of up to 5 years indicate the safety of this strategy for this period, but the exact consequences of strong acid inhibition over a longer period still have to be clarified. At present, all but a few patients with GORD can be managed adequately by medical therapy.
Similar content being viewed by others
References
Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis 1976; 21: 953–6
Locke GR, Talley NJ, Fett SL, et al. The prevalence and impact of gastroesophageal reflux disease in the United States: a population-based study. Gastroenterology 1994; 106: A15
Gallup survey on heartburn across America. Princeton, NJ: The Gallup Organization, 24 March 1988
Graham DY, Smith JL, Patterson DJ. Why do apparently healthy people use antacid tablets?. Am J Gastroenterol 1983; 78: 257–60
Traube M. The spectrum of the symptoms and presentations of gastroesophageal reflux disease. Gastroenterol Clin North Am 1990; 19: 609–16
Castell DO. Introduction to pathophysiology of gastroesophageal reflux disease. In: Castell DO, Wu WC, Ott DJ, editors. Gastroesophageal reflux disease: pathogenesis, diagnosis, therapy. New York: Futura Publishing 1985: 3–9
Mittal RK. Current concepts of the antireflux barrier. Gastroenterol Clin North Am 1990; 3: 501–16
Timmer R, Breumelhof R, Nadorp JHSM, et al. Recent advances in the pathophysiology of gastroesophageal reflux disease. Eur J Gastroenterol Hepatol 1993; 5: 485–91
Hetzel D. Medical treatment of reflux oesophagitis. Gullet 1993; 3 Suppl.: 60–9
Tytgat GNJ, Bianchi Porro G, Feussner H, et al. Long-term strategy for the treatment of gastro-oesophageal reflux disease. Gastroenterol Int 1991; 4: 21–32
Heading RC, Eaves NR. Aims of treatment in gastroesophageal reflux disease. In: Scarpignato C, editor. Advances in drug therapy of gastroesophageal reflux disease. Basel: Karger, 1992: 1–10
Harvey RF, Gordon PC, Hadley N, et al. Effects of sleeping with the bed-head raised and of ranitidine in patients with severe peptic oesophagitis. Lancet 1987; 2: 1200–3
Hamilton JW, Boisen RJ, Yamamoto DT, et al. Sleeping on a wedge diminishes exposure of the esophagus to refluxed acid. Dig Dis Sci 1988; 33: 518–22
Higgs RH, Smith RD, Castell DO. Gastric alkalinization: effect on lower esophageal sphincter pressure and serum gastrin. N Engl J Med 1974; 291: 486–8
Malmud LS, Fisher RS. Quantization of gastroesophageal reflux before and after therapy using the gastroesophageal reflux scan. South Med J 1978; 71: 10
Castell DO, Dalton CB, Becker D, et al. Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal strength antacid. Dig Dis Sci 1992; 37: 589–93
Graham DY, Lanza F, Dorsch ER. Symptomatic reflux esophagitis: a double-blind controlled comparison of antacids and alginate. Curr Ther Res 1977; 22: 653–5
Weberg R, Berstad A. Symptomatic effect of a low-dose antacid regimen in reflux oesophagitis. Scand J Gastroenterol 1989; 24: 401–6
McHardy G. A multicentric, randomized clinical trial of Gaviscon in reflux esophagitis. South Med J 1978; 71: 16–21
Furman D, Mensh R, Winan G. A double-blind trial comparing high dose liquid antacid to placebo and cimetidine in improving symptoms and objective parameters of gastroesophageal reflux. Gastroenterology 1982; 82: 1062–4
Graham DY, Patterson DJ. Double-blind comparison of liquid antacid and placebo in the treatment of symptomatic reflux esophagitis. Dig Dis Sci 1983; 83: 559–65
Grove O, Bekker C, Jeppe Hansen MG, et al. Ranitidine and high-dose antacid in reflux oesophagitis: a randomized, placebo controlled trial. Scand J Gastroenterol 1985; 20: 457–61
Ward AE. Comparative study of Algicon® versus Gaviscon® in symptomatic gastroesophageal reflux. Br J Clin Pract 1989; 43 Suppl. 66: 52–5
Maxton DG, Miller JP, Whorwell PJ, et al. A study of Algicon®, an antacid alginate preparation in patients with reflux oesophagitis. Br J Clin Pract 1988; 42: 368–71
Kitchin LI, Castell DO. Rationale and efficacy of conservative therapy for gastroesophageal reflux disease. Arch Intern Med 1991; 151: 448–54
Tarnawski A, Erickson RA. Sucralfate — 24 years later: current concepts of its protective and therapeutic actions. Eur J Gastroenterol Hepatol 1991; 3: 795–810
Weiss W, Brunner H, Buttner GR, et al. Therapie der Refluxoesophagitis mit Sucralfat. Dtsch Med Wochenschr 1983; 108: 1706–11
Williams RM, Orlando RC, Bozymski EM, et al. Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis. Am J Med 1987; 83 Suppl. 3B: 61–6
Carling L, Cronstedt J, Engqvist A, et al. Sucralfate versus placebo in reflux esophagitis: a double-blind multicenter study. Scand J Gastroenterol 1988; 23: 1117–24
Hameeteman W, Van de Boomgaard DM, Dekker W, et al. Sucralfate versus cimetidine in reflux esophagitis: a single-blind multicenter study. J Clin Gastroenterol 1987; 9: 390–4
Tytgat GNJ. Clinical efficacy of sucralfate in reflux esophagitis, comparison with cimetidine. Am J Med 1987; 83 Suppl. 3B: 38–42
Simon B, Dammann HG, Müller P. Sucralfate in the treatment of reflux esophagitis in adults: an update. Scand J Gastroenterol 1989; 24 Suppl. 156: 37–41
Simon B, Müller P. Comparison of the effect of sucralfate and ranitidine in reflux esophagitis. Am J Med 1987; 83 Suppl. 3B: 43–7
Ros E, Toledo V, Bordas JM, et al. Healing of erosive oesophagitis with sucralfate and cimetidine: influence on pretreatment of lower oesophageal sphincter pressure and serum pepsinogen I levels. Am J Med 1991; 91 Suppl. 2A: 107S–13S
Bremner CG, Marks IN, Segal I, et al. Reflux oesophagitis therapy: sucralfate versus ranitidine in a double blind multicenter study. Am J Med 1991; 91 Suppl. 2A: 119S–122S
Elsborg L, Jorgenson F. Sucralfate versus cimetidine in reflux esophagitis: a double blind study. Scand J Gastroenterol 1991; 26: 146–50
Schotborgh RH, Hameeteman W, Dekker W, et al. Combination therapy of sucralfate and cimetidine, compared with sucralfate monotherapy, in patients with peptic reflux esophagitis. Am J Med 1989; 86 Suppl. 6A: 77–80
Herrera JL, Shay SS, McCabe M, et al. Sucralfate used as adjunctive therapy in patients with severe peptic esophagitis: a random double blind controlled trial [abstract]. Gastroenterology 1989; 96: A207
Vermeyden JR, Tytgat GNJ, Schotborgh RH, et al. Combination therapy of sucralfate and ranitidine, compared with sucralfate monotherapy in patients with peptic reflux esophagitis. Scand J Gastroenterol 1992; 27: 81–4
Orlando RC. Sucralfate therapy and reflux esophagitis: an overview. Am J Med 1991; 91 Suppl. 2A: 123–4
Ramirez B, Richter JE. Review article: promotility drugs in the treatment of gastro-oesophageal reflux. Aliment Pharmacol Ther 1993; 7: 5–20
Verlinden M. Review: a role for gastrointestinal prokinetic agents in the treatment of reflux oesophagitis?. Aliment Pharmacol Ther 1989; 3: 113–33
Savary M, Miller G. The esophagus — handbook and atlas of endoscopy. Solothurn, Switzerland: Verlag Gassmann AG, 1978
Wienbeck M. The ranpride study group: does cisapride added to H2 receptor blocking treatment improve healing rates? [abstract]. Digestion 1986; 34: 144
Hüttemann W. Cisapride in esophagitis: a placebo controlled trial [abstract]. Digestion 1986; 34: 143–4
Baldi F, Bianchi Porro G, Dobrilla G, et al. Cisapride versus placebo in reflux esophagitis: a multicenter double blind trial. J Clin Gastroenterol 1988; 10: 614–8
Janisch HD, Hüttemann W, Bouzo MH. Cisapride versus ranitidine in the treatment of reflux esophagitis. Hepatogastroenterology 1988; 35: 125–7
Galmiche JP, Brandstätter G, Evreux M, et al. Combined therapy with cisapride and cimetidine in severe reflux oesophagitis: a double blind placebo-controlled trial. Gut 1988; 29: 675–81
Lepoutre L, Van Der Spek P, Vanderlinden I, et al. Healing of grade II and III oesophagitis through motility stimulation with cisapride. Digestion 1990; 45: 109–14
Galmiche JP, Fraitag B, Filoche B, et al. Double blind comparison of cisapride and cimetidine in treatment of reflux esophagitis. Dig Dis Sci 1990; 35: 649–55
Evreux M, Filoche B, Fournet J, et al. Endoscopic and clinical evaluation of cisapride and cimetidine in reflux oesophagitis. Gastroenterology 1988; 94: A120
Maleev A, Mendizova A, Popov P, et al. Cisapride and cimetidine in the treatment of erosive esophagitis. Hepatogastroenterol 1990; 37: 403–7
Geldof H, Hazelhoff B, Otten MH. Two different dose regimens of cisapride in the treatment of reflux oesophagitis: a double-blind comparison with ranitidine. Aliment Pharmacol Ther 1993; 7: 409–15
Wienbeck M, Ranpride Group II. Does motor stimulation by cisapride added to acid inhibition by H2 receptor blockade improve healing rates in patients with reflux esophagitis? Abstract of the World Congresses of Gastroenterology; 1990; Sydney. Abingdon: Medicine Group (UK) Ltd, 1990
Dodds W, Champion M, Orr W, et al. Oral cisapride in GERD: a double blind placebo controlled multicenter trial. Gastroenterology 1989; 96: A126
de Micco M, Berenson M, Wu W, et al. Cisapride in the treatment of GERD: a double blind placebo controlled multicenter dose response trial. Gastroenterology 1992; 102: A59
Faraqui S, Sigmund C, Smith R, et al. Cisapride in the treatment of GERD: a double blind placebo controlled multicenter dose response trial. Gastroenterology 1992; 102: A66
Blum AL, Adami B, Bouzo MH, et al. Effect of cisapride on relapse of esophagitis: a multinational, placebo-controlled trial in patients healed with an antisecretory drug. Dig Dis Sci 1993; 38: 551–60
Tytgat GNJ, Anker Hansen OJ, Carling L, et al. Effect of cisapride on relapse of reflux oesophagitis, healed with an anti-secretory drug. Scand J Gastroenterol 1992; 27: 175–83
Toussaint J, Gossuin A, Deruyttere M, et al. Healing and prevention of relapse reflux oesophagitis by cisapride. Gut 1991; 32: 1280–5
Tytgat GNJ, Nio CY. The medical therapy of reflux oesophagitis. Ballière’s Clin Gastroenterol 1987; 1: 1–17
Koelz HR. Treatment of reflux esophagitis with H2-blockers, antacids and prokinetic drugs: an analysis of randomized clinical trials. Scand J Gastroenterol 1989; 24 Suppl. 156: 25–36
Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases. N Engl J Med 1990; 323: 1749–55
Sontag SJ. The medical treatment of reflux esophagitis. Role of antacids and acid inhibition. Gastroenterol Clin North America 1990; 19: 683–712
Bell NJV, Hunt RH. Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease. Gut 1992; 33: 118–24
Klinkenberg-Knol EC. Recent advances in the diagnosis and management of gastro-oesophageal reflux disease [thesis]. VU University Press: Amsterdam, 1990
Meuwissen SGM, Klinkenberg-Knol EC. Treatment of reflux esophagitis with H2 receptor antagonists. Scand J Gastroenterol 1988; 23 Suppl. 146: 201–13
Behar J, Brand DL, Brown FC, et al. Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double-blind controlled trial. Gastroenterology 1978; 74: 441–8
Wesdorp E, Bartelsman J, Pape K, et al. Oral cimetidine in reflux esophagitis: a double-blind controlled trial. Gastroenterology 1978; 74: 821–4
Powell-Jackson P, Barkley H, Northfield TC. Effect of cimetidine on symptomatic gastro-oesophageal reflux. Lancet 1978; 2: 1068–9
Bright-Asare P, El-Bassoussi M. Cimetidine, metoclopramide or placebo in the treatment of symptomatic gastro-oesophageal reflux. J Clin Gastroenterol 1980; 2: 149–56
Fiasse R, Hanin C, Lepot A, et al. Controlled trial of cimetidine in reflux esophagitis. Dig Dis Sci 1980; 25: 750–5
Farup PG, Weberg R, Berstad A, et al. Low-dose antacids versus 400 mg cimetidine twice daily for reflux oesophagitis. Scand J Gastroenterol 1990; 25: 315–20
Goy SG, Maynard JH, McNaughton WM, et al. Ranitidine and placebo in the treatment of reflux oesophagitis: a double-blind randomized trial. Med J Aust 1983; 2: 558–61
Wesdorp ICE, Dekker W, Klinkenberg-Knol EC. Treatment of reflux oesophagitis with ranitidine. Gut 1983; 24: 921–4
Hine KR, Holmes G, Melikian V, et al. Ranitidine in reflux oesophagitis. Digestion 1984; 29: 119–23
Sherbaniuk R, Wensel R, Bailey R, et al. Ranitidine in the treatment of symptomatic reflux disease. J Clin Gastroenterol 1984; 6: 9–15
Lehtola J, Niemela S, Martikainen J, et al. Ranitidine, 150mg three times a day, in the treatment of reflux oesophagitis: a placebo-controlled, double-blind study. Scand J Gastroenterol 1986; 21: 175–80
Johansson KE, Boeryd B, Johansson K, et al. Double-blind crossover study of ranitidine and placebo in gastro-oesophageal reflux disease. Scand J Gastroenterol 1986; 21: 769–78
Sontag S, Robinson M, McCallum RW, et al. Ranitidine therapy for gastroesophageal reflux disease: results of a large double-blind trial. Arch Intern Med 1987; 147: 1485–91
Roufail W, Belsito A, Robinson M, et al. Ranitidine for erosive oesophagitis: a double-blind, placebo-controlled study. Aliment Pharmacol Ther 1992; 6: 597–607
Cloud ML, Offen WW, Robinson M. Nizatidine versus placebo in gastroesophageal reflux disease: a 12-week, multicenter, randomized, double-blind study. Am J Gastroenterol 1991; 86: 1735–42
Cloud ML, Offen WW, et al. Nizatidine versus placebo in gastroesophageal reflux disease. Dig Dis Sci 1992; 37: 865–74
Quik RFP, Cooper MJ, Gleeson M, et al. A comparison of two doses of nizatidine versus placebo in the treatment of reflux oesophagitis. Aliment Pharmacol Ther 1990; 4: 201–11
Dobrilla G, Chiloi F, Tafner G, et al. Treatment of erosive reflux oesophagitis: a double-blind multicentre trial with nizatidine 300mg bid versus placebo. Ital J Gastroenterol 1992; 24: 338–41
Sabesin SM, Berlin RG, Humphries TJ, et al. Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Arch Intern Med 1991; 151: 2394–400
Robinson M, Decktor DL, Stone RC, et al. Famotidine (20mg) b.d. relieves gastroesophageal reflux symptoms in patients without erosive esophagitis. Aliment Pharmacol Ther 1991; 5: 631–43
Bovero E, Poletti M, Iaquinto G, et al. Famotidine in the management of acid-reflux oesophagitis: a multicentre study. Hepatogastroenterology 1990; 37: 145–8
Wesdorp ICE, Dekker W, Festen HPM. Efficacy of famotidine 20mg twice a day versus 40mg twice a day in the treatment of erosive or ulcerative reflux esophagitis. Dig Dis Sci 1993; 38: 2287–93
Johnson NJ, Boyd EJS, Mills JG, et al. Acute treatment of reflux esophagitis: a multicenter trial to compare 150mg ranitidine b.d. with 300mg ranitidine q.d.s. Aliment Pharmacol Ther 1989; 3: 259–66
Thanik K, Chey WY, Shak A, et al. Bethanechol or cimetidine in the treatment of symptomatic reflux esophagitis: a double-blind control study. Arch Intern Med 1982; 142: 1497–81
Guslandi M, Tesoni PA, Passaretti S, et al. Ranitidine versus metoclopramide in the medical treatment of reflux esophagitis. Hepatogastroenterology 1983; 30: 96–8
Fielding JF, Doyle GD. Comparison between ranitidine and cimetidine in the treatment of reflux oesophagitis. Irish Med J 1984; 77: 356–7
Koelz HR, Birchler R, Bretzholz A, et al. Healing and relapse of reflux esophagitis during treatment with ranitidine. Gastroenterology 1986; 91: 1198–205
Berlin R, Ebel D, Cook T. Famotidine 20mg hs and 40mg hs vs placebo in the maintenance therapy of reflux esophagitis: resuits of a double-blind, multicenter trial. Gastroenterology 1989; 96: A39
Pace F, Lazzeroni M, Bianchi Porro G. Failure of sucralfate in the treatment of refractory esophagitis versus high-dose famotidine: an endoscopic study. Scand J Gastroenterol 1991; 26: 491–4
Sontag SJ. Rolling review: gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1993; 7: 293–312
Lieberman DA, Keefe EB. Treatment of severe reflux esophagitis with cimetidine and metoclopramide. Ann Intern Med 1986; 104: 21–6
Kaul B, Petersen H, Erichsen H, et al. Gastroesophageal reflux disease: acute and maintenance treatment with cimetidine. Scand J Gastroenterol 1986; 21: 139–45
Collen MJ, Johnson DA. Correlation between basal acid output and daily ranitidine dose required for therapy in Barrett’s esophagus. Dig Dis Sci 1992; 37: 570–6
Pace F, Sangeletti O, Bianchi Porro G. Short and long term effect of two different dosages of ranitidine in the therapy of reflux oesophagitis. Ital J Gastroenterol 1990; 22: 28–32
Schaub N, Thomas JM, Misciewisz JJ, et al. Investigation of ranitidine 150mg bd or 300mg bd in the treatment of reflux disease. Hepatogastroenterology 1986; 33: 208–13
Bianchi Porro G, Pace F, Lazzaroni M. Esophagitis healing with ranitidine. Gastroenterology 1987; 92: 2051–2
Temple JG, Bradby GVH, O’Connor F, et al. Cimetidine and metoclopramide in oesophageal reflux disease. BMJ 1983; 286: 1863–4
Wienbeck M. Does cisapride added to H2-receptor-blocking treatment improve healing rates in patients with esophagitis? [abstract]. Digestion 1986; 34: 144
Fellenius E, Berglindh T, Sachs G, et al. Substituted benzimidazoles inhibit acid secretion by blocking H+/K+-ATPase. Nature 1981; 290: 159–61
Mohamed AH, Hunt RH. The rationale of acid suppression in the treatment of acid-related disease. Aliment Pharmacol Ther 1994; 8 Suppl. 1: 3–10
Bardhan KD, Long R, Hawkey CJ, et al. Lansoprazole, a new proton pump inhibitor, versus ranitidine in the treatment of reflux oesophagitis. Gut 1990; 31: A1189
Bate CM, Keeling PWN, O’Morain C, et al. Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic and histological evaluations. Gut 1990; 31: 968–72
Benhaim MC, Evreux M, Salducci J, et al. Lansoprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial. Gastroenterology 1990; 98: A20
Dehn TCB, Shepherd HA, Colin-Jones D, et al. Double-blind comparison of omeprazole (40mg od) versus cimetidine (400mg qd) in the treatment of symptomatic erosive reflux oesophagitis, assessed endoscopically, histologically and by 24h pH monitoring. Gut 1990; 31: 509–13
Havelund T, Laursen LS, Skoubo-Kristensen E, et al. Omeprazole and ranitidine in the treatment of reflux oesophagitis: double-blind comparative trial. BMJ 1988; 296: 89–92
Italian Reflux Oesophagitis Study Group. Omeprazole produces significantly greater healing of erosive or ulcerative reflux oesophagitis than ranitidine. Eur J Gastroenterol Hepat 1991; 3: 511–7
Klinkenberg-Knol EC, Festen HPM, Jansen JMBJ, et al. Double blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. Lancet 1987; 1: 349–50
Koop H, Classen W, Schepp W, et al. Comparison of pantoprazole and ranitidine in reflux oesophagitis: a German multicenter study. Gastroenterology 1993; 104: A123
Robinson M, Kogut D, Jennings D, et al. Lansoprazole heals erosive reflux esophagitis better than ranitidine. Gastroenterology 1992; 102: A153
Sandmark S, Carlsson R, Fausa O, et al. Omeprazole or ranitidine in the treatment of reflux esophagitis. Scand J Gastroenterol 1988; 23: 625–32
Vantrappen G, Rutgeerts L, Schurmans P, et al. Omeprazole (40mg) is superior to ranitidine treatment of ulcerative reflux esophagitis. Dig Dis Sci 1988; 33: 523–9
Zeitoun P, Rampal P, Barbier P, et al. Omeprazole (20 mg/j) compare à ranitidine (150 mg 2 fois/j) dans le traitement de l’oesophagite par reflux. Gastroenterol Clin Biol 1989; 13: 457–62
Hetzel DJ, Dent J, Reed WD, et al. Healing and relapse of severe peptic oesophagitis after treatment with omeprazole. Gastroenterology 1988; 95: 903–12
Sontag SJ, Hirschowitz BI, Holt S, et al. Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: The US multicenter study. Gastroenterology 1992; 102: 109–18
Laursen LS, Bondesen S, Hansen J, et al. Omeprazole 20mg or 40mg daily for the treatment of gastroesophageal reflux disease? A double blind comparative study. Gastroenterology 1992; 102: A110
Maton PN. Omeprazole. N Engl J Med 1991; 324: 965–75
Holt S, Howden CW. Omeprazole-Overview and opinion. Dig Dis Sci 1991; 36: 385–93
Bardhan KD. Omeprazole in the treatment of gastroesophageal reflux disease. In: Scarpignato C, editor. Advances in drug therapy of gastroesophageal reflux disease. Front Gastrointest Res. Basel: Karger, 1992; 20: 246–306
Barradell LB, Faulds D, McTavish D. Lansoprazole: a review of its pharmocodynamic and pharmacokinetic properties and its therapeutic efficacy in acid related disorders. Drugs 1992; 44: 225–50
Berstad A, Hatlebakk JG. Lansoprazole in the treatment of reflux oesophagitis: a survey of clinical studies. Aliment Pharmacol Ther 1993; 7 Suppl. 1: 34–37
Bader JP, Delchier JC. Clinical efficacy of pantoprazole compared with ranitidine. Aliment Pharmacol ther 1994; 8 Suppl. 1: 47–52
Klinkenberg-Knol EC. The management of severe, therapy-resistant, reflux oesophagitis. Gullet 1993; 3 Suppl.: 70–5
Bardhan KD, Morris P, Thompson M, et al. Omeprazole in the treatment of erosive oesophagitis refractory to high dose cimetidine and ranitidine. Gut 1990; 31: 745–9
Bardhan KD, Cherian P, Jones RB, et al. H2RA-refractory erosive esophagitis: efficacy of long term omeprazole maintenance therapy. Gastroenterology 1994; 106: A46
Bianchi Porro G, Pace F, Sangaletti O. Omeprazole or ranitidine at standard or doubled doses in the treatment of patients with refractory reflux oesophagitis. Gut 1990; 31: A1189
Brunner G, Creutzfeldt W, Harke U, et al. Therapy with omeprazole in patients with peptic ulcerations resistant to extended high-dose ranitidine treatment. Digestion 1988; 39: 80–90
Ching CK, Shaheen MZ, Holmes GKT. Is omeprazole more effective in the treatment of resistant reflux oesophagitis and associated peptic stricture?. Gastroenterology 1990; 98: A30
Dent J, Klinkenberg-Knol EC, Elm G, et al. Omeprazole in the long term management of patients with reflux oesophagitis refractory to histamine H2 receptor antagonists. Gastroenterol Int 1988; 1 Suppl.: 847
Fiasse R, Druez P, Coppens JP, et al. Omeprazole in the treatment of patients with severe reflux oesophagitis not responding to H2 receptor antagonists and ineligible for surgery. Acta Gastroenterol Belg 1990; 53: 573–84
Hill AD, O’Donaghue DP. Omeprazole in refractory reflux oesophagitis. Gullet 1991; 1: 81–3
Klinkenberg-Knol EC, Festen HPM, Jansen JBMJ, et al. The efficacy and safety of long term treatment with omeprazole of patients with refractory reflux esophagitis. Ann Intern Med 1994; 121: 161–7
Koop H, Hotz J, Pommer G, et al. Prospective evaluation of omeprazole treatment in reflux oesophagitis refractory to high doses of H2-receptor antagonists. Aliment Pharmacol Ther 1990; 4: 593–9
Lee FI, Isaacs PET. Barrett’s ulcer: response to standard dose ranitidine, high dose ranitidine, and omeprazole. Am J Gastroenterol 1988; 83: 914–7
Lundell L, Backman L, Ekstrom P, et al. Omeprazole or high dose ranitidine in the treatment of patients with reflux esophagitis not responding to standard doses of H2 receptor antagonists. Aliment Pharmacol Ther 1990; 4: 145–50
Marciano-D’Amore DA, Paterson WG, Da Costa LR, et al. Omeprazole in H2-receptor antagonist-resistant reflux esophagitis. J Clin Gastroenterol 1990; 12: 616–20
Sontag S, Hendrix T, Hirschowitz B, et al. Omeprazole for esophagitis and ulcer refractory to H2 blockers. Gastroenterology 1988; 94: A436
Klinkenberg-Knol EC, Meuwissen SGM. Combined gastric and oesophageal 24-hour pH monitoring and oesophageal manometry in patients with reflux disease, resistant to treatment with omeprazole. Aliment Pharmacol Ther 1990; 4: 485–95
Hendel L, Hage E, Hendel J, et al. Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis. Aliment Pharmacol Ther 1992; 6: 565–77
Kuo B, Castell DO. Omeprazole 20 mg BID provides better acid suppression than a single dose of 40 mg. Gastroenterology 1994; 106: A1034
Klinkenberg-Knol EC, Jansen JB, Lamers CB, et al. Temporary cessation of long-term maintenance treatment with omeprazole in patients with H2-receptor-antagonist-resistant reflux oesophagitis: effects on symptoms, endoscopy, serum gastrin, and gastric acid output. Scand J Gastroenterol 1990; 25: 1144–50
Bianchi Porro G, Pace F. Rationale and efficacy of medical therapy for gastro-oesophageal reflux disease. J Int Med 1993; 234: 387–96
Hetzel DJ, Dent J, Reed WD, et al. Healing and relapse of severe peptic oesophagitis after treatment with omeprazole. Gastroenterology 1988; 95: 903–12
Laursen LS, Bondesen S, Hansen J, et al. Omeprazole 10mg or 20mg daily for the prevention of relapse in gastroesophageal reflux disease? A double blind comparative study [abstract]. Gastroenterology 1992; 102: A109
Ottenjan R, Siewert JR, Heilman, et al. Treatment of reflux oesophagitis: results of a multicentre study. In: Siewert JR, Hölscher AH, editors. Diseases of the oesophagus. Berlin: Springer Verlag, 1988: 1123–9
Amstrong D, Blum AL, Rezitic Study Group. Full dose H2 receptor antagonist prophylaxis does not prevent relapse of reflux oesophagitis. Gut 1989; 30: A1494
Stein DT, Simon TJ, Berlin RG, et al. Controlling 24 hour esophageal acid exposure in patients with healed erosive esophagitis prevents endoscopic recurrence and symptomatic deterioration: results of a 6 month, randomized, double blind, US placebo controlled trial comparing famotidine 20mg bid and 40mg bid. Gastroenterology 1991; 100: A167
Bank S, Magier D, Greenberg R, et al. Alternate day omeprazole maintenance therapy in H2RA resistant esophagitis — clinical, gastrin and ECL effects for up to 3 years [abstract]. Gastroenterology 1992; 102: A35
Robinson M, Lanza F, Lansoprazole Study Group. Lansoprazole for one year prevents recurrence of erosive reflux esophagitis. Gastroenterology 1994; 106: A166
Toledo-Pimentel V, Ros E, Bordas JM, et al. Reflux esophagitis refractory to high-dose histamine H2-antagonists: healing with omeprazole. Gastroenterology 1992; 102: A179
Zeitoun P, Barbier P, Cayphas J-P, et al. Comparison of two dosage regimens of omeprazole — 10mg once daily and 20mg weekends — as prophylaxis against recurrence of reflux oesophagitis. Hepatogastroenterology 1989; 36: 279–80
Lundell L, Backman L, Ekstrom P, et al. Prevention of relapse of reflux esophagitis after endoscopic healing: the efficacy and safety of omeprazole compared with ranitidine. Scand J Gastroenterol 1991; 26: 248–56
Dent J, Yeomans ND, Mackinnon M, et al. Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis: a controlled double blind trial of their efficacy and safety. Gut 1994; 35: 590–8
Isal JP, Zeitoun P, Barbier P, et al. Comparison of two dosage regimens of omeprazole — 10mg once daily and 20mg weekends — as prophylaxis against recurrence of reflux esophagitis [abstract]. Gastroenterology 1990; 98: A63
Bardhan KD, Daly MJ, Singh S, et al. Refractory erosive oesophagitis: results of maintenance treatment with high dose H2 receptor antagonists or omeprazole [abstract]. Gut 1990; 31: A602: Gastroenterology 1990; 98: A18
Lundell L. Acid suppression in the long-term treatment of peptic stricture and Barrett’s oesophagus. Digestion 1992; 51 Suppl. 1: 49–58
Marks R, Richter JE, Koehler R, et al. Does medical therapy improve dysphagia in patients with peptic strictures and oesophagitis?. Gastroenterology 1992; 102: A118
Swarbrick ET, Gough AL, Christian J, et al. Prevention of recurrence of oesophageal stricture: a comparative study of lansoprazole and high dose ranitidine. Gastroenterology 1994; 106: A189
Gore S, Healy CJ, Sutton R, et al. Regression of columnar lined (Barrett) oesophagus with continuous omeprazole therapy. Aliment Pharmacol Ther 1993; 7: 623–8
Iqbal TH, Neumann CS, Gearty JC, et al. Omeprazole 20mg daily for 12–24 months in the treatment of patients with Barrett’s esophagus. Gastroenterology 1994; 106: A99
Brossard E, Ollyo JB, Fontoillet Ch, et al. Barrett’s esophagus may still progress under treatment. Gastroenterology 1994; 106: A57
Galmiche J-P, Dumas R, Boyer J, et al. Regression of Barrett’s mucosa with long-term omeprazole treatment [abstract]. Endoscopy 1994; 26: 385
Colin-Jones DG, Langman MJS, Lawson DH. Postmarketing surveillance of the safety of cimetidine: 10 year mortality report. Gut 1992; 33: 1280–4
Colin-Jones DG, Langman MJS, Lawson DH, et al. Post-cimetidine surveillance for up to ten years: incidence of carcinoma of the stomach and oesophagus. Q J Med 1991; 78: 13–9
Solvell L. The clinical safety of omeprazole. Scand J Gastroenterol 1989; 24 Suppl. 166: 106–10
Arnold R. Safety of proton pump inhibitors — an overview. Aliment Pharmacol Ther 1994; 8 Suppl. 1: 65–70
Koop H, Arnold R. Long-term maintenance treatment of reflux esophagitis with omeprazole. Dig Dis Sci 1991; 36: 552–7
Lamberts R, Creutzfeldt W, Struber HG, et al. Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis. Gastroenterology 1993; 104: 1356–70
Tielemans Y, Hakanson R, Sundler F, et al. Gastrin stimulates the self-replication rate of enterochromaffin-like cells in the rat stomach. Gastroenterology 1989; 96: 723–9
Havu N, Maaroos H-I, Sipponen P. Argyrophil cell hyperplasia associated with chronic corpus gastritis in gastric ulcer disease. Scand J Gastroenterol 1991; 26 Suppl. 186: 90–4
Vigneri S, Termini R, Scialabba A, et al. Omeprazole long-term treatment for duodenal ulcer effects on the gastric distribution of helicobacter pylori. Acta Gastroenterol Belg 1993; 56 Suppl.: 147
Kuipers EJ, Uyterlinde AM, Nelis GF, et al. Long term follow up of Helicobacter pylori associated gastritis. Gastroenterology 1994; 106: A113
Festen H, Klinkenberg-Knol EC, Kuipers E, et al. Cobalamin absorption during omeprazole treatment: short and long-term studies. Gastroenterology 1993; 104: A77
Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B-12). Ann Intern Med 1994; 120: 211–5
Koop H. Metabolic consequences of long-term inhibition of acid secretion by omeprazole. Aliment Pharmacol Ther 1992; 6: 399–406
Minoli G, Strocchi E, Lenoci N. Long term omeprazole treatment and iron, ferritin and vitamin B12 levels. Gastroenterology 1994; 106: A140
Hillman A, Bloom BS, Fendrick AM, et al. Cost and quality effects of alternative treatments for persistent gastroesophageal reflux disease. Arch Intern Med 1992; 152: 1467–72
Bate CM, Richardson PDI. A one year model for the cost effectiveness of treating reflux oesophagitis. Br J Med Econ 1992; 2: 5–11
Hamelin B, Arnould B, Barbier JP, et al. Cost-effectiveness comparison between omeprazole and ranitidine for treatment of reflux oesophagitis. Gastroenterology 1994; 106: A88
De Boer WA, Tytgat GNJ. Review article: drug therapy for reflux oesophagitis. Aliment Pharmacol Ther 1994; 8: 147–57
Hixson LJ, Kelley CL, Jones WN, et al. Current trends in the pharmacotherapy for gastroesophageal reflux disease. Arch Intern Med 1992; 152: 717–23
Johnson DA. Medical therapy for gastroesophageal reflux disease. Am J Med 1991; 92 Suppl. 5A: 88S–97S
Fennerty MB, Sampliner RE. Medical therapy for gastroesophageal reflux disease. Arch Intern Med 1991; 151: 2365–6
Dehn TCB. Surgery for uncomplicated gastroesophageal reflux. Gut 1992; 33: 293–4
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Klinkenberg-Knol, E.C., Festen, H.P.M. & Meuwissen, S.G.M. Pharmacological Management of Gastro-Oesophageal Reflux Disease. Drugs 49, 695–710 (1995). https://doi.org/10.2165/00003495-199549050-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199549050-00005