• Use single drugs or a combination of drugs, according to the predominant symptoms of the individual.
• Consider an antispasmodic, alongside dietary and lifestyle advice, for all people with irritable bowel syndrome, and in particular those with pain occurring as spasm.
• For people with constipation, consider treatment with a laxative.
• Bulk-forming laxatives are preferred (e.g. ispaghula or sterculia).
• For people who cannot tolerate a bulk-forming laxative, or who need an additional laxative, offer a macrogol (polyethylene glycol) or a stimulant laxative (for short-term use only).
• Lactulose is not recommended.
• For people with diarrhoea, consider treatment with an antimotility drug.
• Loperamide is the antimotility drug of choice.
• Advise people to adjust the dose of laxative or antimotility drug according to response. The aim is to produce a soft, well-formed stool.
• If symptoms do not respond to first-line treatment, consider a trial of a low dose tricyclic antidepressant (for pain relief).
• Start treatment at a low dose (equivalent to 5–10 mg amitriptyline at night).
• Review 4 weeks after starting treatment and titrate the dose up if necessary (the usual maximum dose is equivalent to 30 mg amitriptyline at night).
• Continue to review every 6–12 months.
• Consider a selective serotonin reuptake inhibitor if a tricyclic antidepressant has previously been shown to be ineffective.

• Tricyclic antidepressants and selective serotonin reuptake inhibitors are primarily used for the treatment of depression, and are only recommended here for their analgesic effect.

The evidence base on drug treatments in the management of irritable bowel syndrome (IBS) is generally poor. There is a high placebo response to treatment in people with IBS, but this often wears off after initial success. In general, controlled studies are poor showing only moderate responses, and there is a significant risk of positive publication bias as indicated by heterogeneity of trial results.

• These recommendations are consistent with the National Institute for Health and Clinical Excellence guidance Irritable bowel syndrome in adults [National Collaborating Centre for Nursing and Supportive Care, 2008; NICE, 2008].

Basis for recommending antispasmodics

• The Guideline Development Group (GDG) consensus was that antispasmodics should be used as first-line therapy alongside dietary and lifestyle advice for people with IBS, particularly those with pain occurring as spasm.
• Evidence from generally small, heterogeneous studies suggests that antispasmodics improve symptoms of pain, bloating, and bowel habits compared with placebo.
• There does not appear to be a difference in efficacy between antimuscarinics and smooth muscle relaxants, but there is an increase in adverse effects with antimuscarinics compared with smooth muscle relaxants.

Basis for recommending laxatives for constipation in IBS

• Evidence from nine RCTs suggests that fibre is more effective than placebo at improving global symptoms of IBS. Subgroup analysis suggests that soluble fibre is more effective than insoluble fibre. Direct evidence from two RCTs suggests that soluble fibre is more effective than insoluble fibre at improving global symptoms of IBS.
• There is good evidence that laxatives are clinically effective in the management of constipation in IBS. Much of this is indirect evidence from people defined as having simple constipation. However, the GDG considered that many of the participants had IBS, and that the evidence could be extrapolated.
• There was consensus among members of the GDG that IBS is more complex than simple constipation, and that some laxatives (e.g. lactulose) exacerbate the symptoms of IBS and should be avoided by people with IBS.

Basis for recommending loperamide for diarrhoea in IBS

• There is evidence from one study (n = 107) that antimotility drugs (loperamide and co-phenotrope) are effective for the short-term symptomatic relief of diarrhoea in IBS.
• There is some evidence that loperamide is more effective than co-phenotrope.
• There is a limited amount of evidence that loperamide improves global symptoms, pain, and bowel habit in the longer term.
• The GDG also noted that loperamide is widely used and accepted as clinically effective for the treatment of diarrhoea in people with IBS.

Basis for considering a tricyclic antidepressant (TCA) or a selective serotonin reuptake inhibitor (SSRI)

• There is good evidence from six RCTs (n = 434) mainly in people with refractory IBS, showing a significant global improvement in symptoms for both TCAs and SSRIs.
• There is limited evidence from several small studies showing:
• A significant reduction in pain for TCAs compared with placebo.
• A borderline improvement in bowel habit for TCAs compared with placebo.
• There is limited evidence from several small studies showing:
• A significant reduction in pain for SSRIs compared with placebo.
• A borderline improvement in bowel habit for SSRIs compared with placebo.
• No significant difference in bloating for SSRIs compared with placebo.