Table 1.

Characteristics and primary outcomes of randomized, double-blind, placebo controlled clinical trials in irritable bowel syndrome patients

Ref.	IBS population	Selection criteria	Treatment	Dose	Duration	Outcome
Mitchell et al[46]	All subtypes	Modified Rome	Alverine citrate vs placebo	120 mg tid	12 wk	No significant difference compared to placebo
Wittmann et al[48]	All subtypes	Rome III	Alverine citrate +	60 mg tid +	4 wk	Significantly reduced abdominal pain and discomfort compared to placebo
			simethicone vs placebo	300 mg tid		More therapy responders, regardless of stool pattern, compared to placebo
Connel et al[52]	All subtypes		Mebeverine vs placebo	100 mg qid	12 wk	Superior in controlling IBS symptoms compared to placebo
Kruis et al[58]	All subtypes		Mebeverine vs placebo vs Wheat bran	400 mg daily	16 wk	No significant difference compared to placebo
Enck et al[59]	All subtypes		Mebeverine vs placebo vs Dietary fiber		16 wk	Therapy response rate lower than placebo
Everitt et al[61]	All subtypes	Rome III	Mebeverine vs	135 mg tid	6 wk	No significant difference between drugs
			methylcellulose vs placebo with/without cognitive behavioral therapy web site (assisted or not)	3 tbl. bid		Significantly increased enablement at 6 and 12 wk in website group compared to no website group, significantly more participants scored their subjective assessment of global relief as improved at 12 wk in website group compared to no website group.
Baldi et al[69]	Abdominal pain predominant		Otilonium bromide vs placebo	40 mg tid		No significant difference in abdominal pain, bloating and general well-being compared to placebo, but significantly reduced sigmoid motility
Battaglia et al[70]	All subtypes	Drossman	Otilonium bromide vs placebo	40 mg tid	15 wk	Significantly better compared to placebo in reduction of abdominal pain frequency, global score improvement of abdominal pain and discomfort, therapy responder rate, reduced tenderness of the sigmoid colon, higher general well-being and global judgement of investigators; superior in improving severity of diarrhea/constipation, number of evacuations and mucus in stool; more effective in treating diarrhea, but not constipation
Clave et al[72]	All subtypes	Rome II	Otilonium bromide vs placebo	40 mg tid	15 wk	Reduced abdominal pain frequency and bloating and improved stool frequency and patient global assessment compared to placebo; lower symptom recurrence after treatment
Awad et al[85]	All subtypes		Pinaverium bromide vs placebo	50 mg tid		Significantly reduced post-prandial rectal spike amplitude plus frequency and spontaneous recto-anal inhibitory reflex frequency compared to placebo
Chassany et al[98]	All subtypes	Rome II	Phloroglucinol + trimethylphloroglucinol vs placebo	62.2 mg + 80 mg tid	1 wk	Significantly higher relative decrease of pain intensity and responder rate in the phloroglucinol plus trimethylphloroglucinol group compared to placebo; persisting treatment effect in a higher percent of patients treated with phloroglucinol plus trimethylphloroglucinol
Cha et al[99]	IBS-D	Rome III	Phloroglucinol vs placebo	80 mg tid	2 wk	Significantly improved subjects' global assessment and decreased stool frequency

Characteristics and primary outcomes of randomized, double-blind, placebo controlled clinical trials in irritable bowel syndrome (IBS) patients with alverine citrate, mebeverine, otilonium bromide, pinaverium bromide and phloroglucinol. IBS-D: IBS with diarrhea.