This review concluded that over-the-counter therapies for gastro-oesophageal reflux disease are effective in comparison with placebo. The authors’ conclusions should be treated with some caution given the potential for methodological flaws in the meta-analysis, publication bias and the lack of detail about study participants.

To examine the efficacy of over-the-counter (OTC) therapies for gastro-oesophageal reflux disease (GERD).

MEDLINE was searched from 1972 to 2005; the search terms were reported. Reference lists were screened, including abstracts presented at major meetings, and manufacturers in the USA were contacted for unpublished data. Duplicate articles were excluded.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies comparing OTC doses of antacid, combined antacid-alginate or histamine-2 receptor antagonists (H2RAs) with placebo were eligible for inclusion. Studies evaluating high-dose or prescription strength GERD agents were excluded. The interventions assessed in the included studies were: combined antacid-alginate (Gaviscon; two tablets 1 to 3 times daily or 10 mL 4 times daily), aluminium hydroxide/magnesium carbonate (two tablets 3 times daily or 22 to 120 mEq dose per day), famotidine (up to 20 mg/day), ranitidine (75 mg up to 4 times daily), cimetidine (200 mg up to 3 times daily), nizatidine (75 mg up to twice daily). The duration of treatment was 2 to 4 weeks.

Participants included in the review

Inclusion criteria for the study participants were not explicitly stated, but it is clear that studies of adults suffering from GERD were eligible for inclusion. No details were given of the participants in the included studies.

Outcomes assessed in the review

The outcomes of interest were defined as complete and adequate relief of GERD symptoms, subjective global improvement and the use of rescue antacids. Studies that lacked well-defined outcomes were excluded. The outcomes measured in the included studies were: prevention of heartburn; duration without heartburn; heartburn severity; response (good or better); relief of heartburn; onset of relief of heartburn; use of rescue antacids; successfully treated nocturnal symptoms; symptomatic improvement; reduction in reflux or regurgitation.

How were decisions on the relevance of primary studies made?

Two reviewers independently selected studies for inclusion in the review, with any differences resolved by consensus.

Two reviewers independently used the Jadad scale to assess validity. The studies received a score of 0 to 5 based on the reporting of randomisation and allocation concealment procedure, blinding and the handling of drop-outs. Any differences between the reviewers were resolved by consensus.

Two reviewers independently extracted the data in a standardised manner, with any differences resolved by consensus. Data were extracted on each outcome of interest on an intention-to-treat basis.

How were the studies combined?

The studies were combined in a meta-analysis using a random-effects model. For each comparison the absolute benefit increase (ABI: difference between treatment and control events rates), relative benefit increase (RBI: ABI divided by control event rate) and number-needed-to-treat (NNT) were calculated, with 95% confidence intervals (CIs). Odds ratios (ORs) with 95% CIs were calculated for the outcome ‘Use of rescue antacids’. Publication bias was assessed using funnel plots.

How were differences between studies investigated?

A chi-squared test was used to assess statistical heterogeneity (p<0.1 indicated statistically significant heterogeneity between the studies). The I-squared statistic was also calculated (I-squared >50% indicated substantial heterogeneity).

Fourteen RCTs containing 18 comparisons (n>7,000) were included. The total number of participants is unclear as some studies evaluated several comparisons.

H2RAs (10 RCTs).

The mean Jadad score was 3.5 (range: 2 to 5). Single-dose H2RAs were significantly more effective than placebo in preventing heartburn for at least 3 hours after a provocative meal (2 trials; ABI 11.3%, 95% CI: 6.2, 16.5, p<0.0001; RBI 2.7, 95% CI: 1.5, 4.0; NNT 9, 95% CI: 6, 16) and in the patients’ assessment of improved symptoms (2 trials; ABI 16%, 95% CI: 7.9, 23.3, p<0.0001; RBI 0.29, 95% CI: 0.14, 0.41; NNT 6, 95% CI: 4, 13). H2RAs given over 2 to 4 weeks were significantly more effective than placebo for adequate relief of heartburn (4 trials; ABI 10%, 95% CI: 7, 13, p<0.0001; RBI 0.28, 95% CI: 0.19, 0.36; NNT 10, 95% CI: 7, 14). One trial showed that complete relief of heartburn was more likely in the H2RA arm (p<0.001).

H2RAs were significantly more likely than placebo to bring about subjective improvement (4 trials; ABI 12%, 95% CI: 7, 17, p<0.0001; RBI 0.19, 95% CI: 0.13, 0.25; NNT 8, 95% CI: 6, 14). People taking H2RAs were significantly less likely than people taking placebo to require rescue antacids (6 trials; OR 0.59, 95% CI: 0.53, 0.66, p<0.0001).

Antacids (4 RCTs).

The mean Jadad score was 3.5 (range: 2 to 5). People taking antacids were more likely to report subjective improvement (4 trials; ABI 8%, 95% CI: 0, 16, p=0.06; RBI 0.11, 95% CI: 0.03, 0.20; NNT 13, 95% CI: 6, 250), and were significantly less likely than people taking placebo to require rescue antacids (2 trials; OR 0.70, 95% CI: 0.59, 0.84, p<0.0001).

Alginate-antacid combination (Gaviscon, 4 RCTs).

The mean Jadad score was 3.8 (range: 2 to 5). People taking Gaviscon were significantly more likely to report subjective improvement than people taking placebo (3 trials; ABI 26%, 95% CI: 12, 41, p<0.0001; RBI 0.60, 95% CI: 0.25, 0.91; NNT 4, 95% CI: 2, 9). One trial showed that people taking Gaviscon were more likely than those taking placebo to report symptomatic improvement of heartburn within 15 minutes of ingestion (p<0.05).

There was no statistical heterogeneity in any of the comparisons (chi-squared p-values ranged from 0.2 to 0.9; I-squared values ranged from 0 to 40%).

Funnel plots indicated that publication bias may be present.

OTC medicines are effective in the prevention and treatment of GERD symptoms.

This review addressed a well-defined research question and applied explicit inclusion criteria to select relevant studies. Only one (English language) database was searched, which might have led to some relevant studies being missed, and although steps were taken to locate unpublished studies, the funnel plots indicated that publication bias may be present. Steps were taken to minimise bias at the study selection, validity assessment and data extraction stages. Validity was assessed using a validated scale and the results of this assessment presented.

Details of the participants in the included studies were not listed anywhere in the review, which limits the generalisability of the findings. Although statistical heterogeneity was not present, clinical heterogeneity in terms of the participants cannot be ruled out. With several of the included studies having more than one comparison arm, it is not clear what steps the authors took to avoid double-counting of the placebo group which, if not addressed, could lead to the comparisons being given undue weight in the meta-analysis. The authors’ conclusions seem reasonable, but must be treated with some caution given the possibility that participants have been counted twice and the potential for publication bias and clinical heterogeneity.

Practice: The authors suggested that OTC GERD therapies are best suited to people with meal-induced infrequent episodes and people experiencing breakthrough symptoms when taking other long-acting treatments. They pointed out that efficacy in the presence of erosive oesophagitis or safety over a prolonged period of time cannot be assumed.

Research: The authors did not state any implications for further research.

Not externally funded.

This additional published commentary may also be of interest.
Strickland DS. Review: over-the-counter medications are effective for gastro-oesophageal reflux disease. Evid Based Nurs 2007;10:76.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.