Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Cimetidine provided symptomatic relief of dyspepsia

ACP J Club. 1992 Sept-Oct;117:40. doi:10.7326/ACPJC-1992-117-2-040


Source Citation

Johannessen T, Petersen H, Kristensen P, et al. Cimetidine on-demand in dyspepsia. Experience with randomized controlled single-subject trials. Scand J Gastroenterol. 1992 Mar;27:189-95.


Abstract

Objective

To identify individual responders to on-demand cimetidine therapy for nonulcer dyspepsia and compare them with patients taking cimetidine for endoscopically proven peptic ulcer and esophagitis.

Design

Randomized, double-blind, placebo-controlled, multicrossover, n-of-1 trials with timing of medication determined by the patient.

Setting

University department of community medicine, Norway.

Patients

Outpatients, aged 18 to 70 years, referred for endoscopy and requesting treatment for dyspepsia symptoms were eligible unless they had had ulcer complications, required continuous therapy, had recently been treated with histamine-2 antagonists, had other serious disease, or were pregnant or lactating. 68 trials were begun, but 22 trials were not completed (16 patients became symptom-free, and 6 patients [9%] were lost to follow-up or did not comply). Of the included patients, 12 had peptic ulcers; 9 had esophagitis, grades I to III; and 25 had at least 3 dyspeptic symptoms including heartburn, acid regurgitation, and upper abdominal pain.

Intervention

Patients were given 6 doses of cimetidine, 400 or 800 mg, and 6 placebo doses, with the order randomized in pairs. A maximum of 3 doses per day were to be taken at least 6 hours apart for relief of dyspeptic symptoms. The extent of relief over the next 3 to 5 hours was recorded. No other alleviating agents or food was to be consumed before measuring the effect of the dose.

Main outcome measure

Patients judged each dose's effect on symptoms, within 3 to 6 hours, on a 0-to-6-point global scale that measured improvement.

Main results

Aggregated data from all 46 patients showed greater amelioration of symptoms with cimetidine (P < 0.001). Symptoms improved after 149 of 276 placebo doses (54%) compared with 225 of 276 cimetidine doses (82%) {95% CI for difference 20% to 35%}*. Symptoms worsened after 5 of the 276 doses of cimetidine (2%) and 14 of the 276 doses of placebo (5%). 13 of 25 patients (52%) with symptomatic nonulcer dyspepsia, 6 of 12 patients (50%) with peptic ulcer, and 7 of 9 patients (78%) with esophagitis responded to treatment. The mean period in which 34 patients consumed the 12 doses was 46 days.

Conclusion

Cimetidine was effective for ameliorating persistent symptoms in individual patients with nonulcer dyspepsia, peptic ulcer, or esophagitis.

Sources of funding: Norwegian Research Council and Smith Kline & French.

Address for article reprint: Dr. T. Johannessen, Department of Community Medicine and General Practice, Eirik Jarls gate 10, N-7030 Trondheim, Norway.

*Numbers calculated from data in article.


Commentary

Dyspepsia, a poorly defined syndrome of episodic or recurrent upper abdominal discomfort after eating, has an estimated prevalence of 20% to 30% in the general population. The pathophysiology of this disorder is unknown. Postulated mechanisms include gastric acid hypersecretion, gastric motility disorder, Helicobacter pylori infection, and psychogenic stress. The investigation of dyspepsia is limited to patients with systemic signs or symptoms that suggest anatomic disease; otherwise, the treatment of dyspepsia is empiric. Results of previous randomized trials have generally failed to show any advantage of antacids or cimetidine over placebo (1), although a more recent trial found a benefit of cimetidine for relief of pain (2).

Johannessen and colleagues compared on-demand cimetidine with placebo in treating the symptoms of dyspepsia. Their n-of-1 design addresses a limitation of previous studies: A subgroup of responders may have been lost in the random error associated with a majority of nonresponders. Unfortunately, flaws in the methods (4 changes in study design and 2 different dosages of cimetidine) and a P value of 0.20 as the criterion for a positive result of an individual n-of-1 trial limit the conclusions that can be drawn from these results. On the other hand, this study confirms a belief that patients and practitioners have held for years: On-demand therapy is quick and effective for the relief of dyspepsia.

When the trend in the treatment of gastrointestinal diseases seems to be toward more potent drugs such as omeprazole and toward triple-drug regimens such as those used for the eradication of H. pylori, a regimen that used only 6 active pills in an average of 46 days and relieved symptoms over 80% of the time has definite appeal. Yet, confirmatory studies are needed before on-demand therapy can be recommended for these uncomplicated disorders.

I. David Shocket, MD
Washington Hospital CenterWashington, DC, USA

I. David Shocket, MD
Washington Hospital Center
Washington, DC, USA


References

1. Nyrén O, Adami HO, Bates S, et al. N Engl J Med. 1986;314:339-43.

2. Gotthard R, Bodemar G, Brodin U, Jönsson KA. Scand J Gastroenterol. 1988;23:7-18.