Twenty RCTs (n=3,876) were included in the review.
Lactulose (10 RCTs, n=934).
Study quality scores for lactulose trials were between 3 and 10 points (low to moderate quality). For patients with varying degrees of constipation (mild to chronic), lactulose was more effective than placebo, but less effective than PEG or bulk laxative plus senna, at relieving symptoms. There were no statistically significant differences in adverse events associated with lactulose in comparison with placebo or comparator agents. The adverse events most commonly reported were abdominal pain/griping, bloating, diarrhoea and gas. The reasons for discontinuation, where reported, were depression, concurrent effects (unspecified) and intolerance of lactulose.
PEG-3350 (6 RCTs, n=318).
Study quality scores for PEG 3350 trials were between 7 and 10 points (all moderate quality). Overall, PEG-3350 was found to be significantly more effective than placebo in 4 out of 5 studies (n=203), and modestly more effective than lactulose in one study (n=115), at relieving symptoms of constipation (mild to chronic). The most commonly reported adverse event was diarrhoea, but there were no statistically significant differences in adverse events between PEG-3350 and placebo or comparator. No study reported specific reasons for discontinuation.
Tegaserod (2 RCTs, n=2,133).
Study quality scores for tegaserod trials were 13 and 14 points (high quality). Tegaserod was found to be statistically significantly more effective than placebo in patients with long-term constipation. More episodes of diarrhoea were found in the tegaserod group than in the placebo group. These occurred during the first week of treatment, were transient, and did not result in hospitalisation or electrolyte imbalances. Less than 1% discontinued treatment with tegaserod due to diarrhoea.
Lubiprostone (data from abstracts only) (3 RCTs, n=606).
Study quality scores for lubiprostone trials were between 8 and 13 points (moderate to high quality). Overall, there was a statistically significant benefit of lubiprostone compared with placebo in 3 trials of patients with at least a 6-month duration of symptoms. The incidence of nausea was higher in patients receiving lubiprostone than in those receiving placebo. One study showed no statistically significant differences between groups for discontinuation, with two withdrawals in the intervention and placebo groups. Two studies reported more patients discontinuing lubiprostone treatment compared with placebo. Gastrointestinal adverse events were responsible for 75% of withdrawals.