Seventy studies were included (4836 patients), including thirty seven using a parallel design and thirty three using cross-over design.
Use of diagnostic criteria: 17 (24%) trials used standard diagnostic criteria. 16 (23%) trials did not specify diagnostic criteria. 53% studies based diagnosis on a modification of standard criteria and 54 (77%) reported an adequate work up to exclude organic disease.
Methodological flaws included: lack of assessment of baseline comparability and co-intervention; variability in definition of symptoms; magnitude of improvement in global status was not well defined; few studies specified which adverse effects were measured or reported the number of patients experiencing adverse reactions; several outcomes were analysed without appropriate statistical adjustment; and some cross-over trials did not examine for period or sequence effects (or both). Statistical analysis: intention-to-treat (ITT) analysis was performed in most trials (80%). Drop-out rates ranged from 0% to 24% in trials judged to have used an ITT analysis. Only 2 studies reported any power calculation.
Validity: mean quality score was 3.2, median was 3. 28 trials were judged as high quality.
1. Bulking agents (13 RCTs): results were inconsistent with only four trials reporting benefit. Of the 7 high quality RCTs (341 patients), 3 reported benefit in either global status or individual symptoms (ease of stool passage, bowel satisfaction and constipation).
2. Smooth-muscle relaxants (16 RCTs): results were inconsistent though, with 13 RCTs reporting benefit, tended to favour the active drug. All 7 high quality RCTs (601 patients) reported improvement in abdominal pain with 2 trials reporting a significant improvement in constipation. In all but one of the high quality RCTs, anticholinergic side effects were similar between active drug and placebo.
3. Prokinetic agents (6 RCTs): results were inconsistent with only one RCT reporting benefit. Of the 4 high quality RCTs (266 patients), 3 RCTs reported no benefit in global status and 2 reporting no benefit in individual symptoms.
4. Loperamide (4 RCTs): all 4 RCTs reported an improvement in diarrhea and the 2 RCTs that reported global status reported improvement. The 2 high quality RCTs (100 patients) both reported significant improvement in diarrhea, including decreased frequency of bowel movements and improved stool consistency but no improvement in abdominal pain and distention
5. Psychotropic agents (7 RCTs): results were inconsistent with 3 of the 5 RCTs that measured global improvement, reporting benefit and 4 of the 7 RCTs reporting improvement in abdominal pain and diarrhea but none reporting any difference in constipation. Only one high quality RCT (14 patients) was identified and this reported global improvement but did not report on individual symptoms.
6. Other agents: results given below are limited to those from more than one trial. Other results were reported in the review.
a) Ondansetron (2 RCTs, including one high quality RCT with 50 patients): both reported significant improvement in global status and stool consistency in patients with predominant diarrhea but no improvement in abdominal pain and distension.
b) Diphenylhydantoin (2 RCTs, including one high quality RCT with 14 patients): inconsistent results with the one high quality RCT reporting no benefit and the other RCT reporting global improvement.
c) Peppermint oil (3 RCTs, including one high quality RCT with 110 patients): inconsistent results with the high quality RCT reporting improvement and the others reporting no benefit.