Antidepressants are likely to provide more than a placebo effect for those with symptoms of irritable bowel syndrome. Antidepressants improve symptoms in about 60% of those taking them, but two-thirds of that effect may be due to placebo. Psychological therapies, such as talking therapies also appear effective in about half of those offered them but may be partly due to expectations because it is not possible to provide a placebo control.
Irritable bowel syndrome is a chronic disorder of the gut which commonly causes pain, bloating, stomach cramps and diarrhoea or constipation. Despite these symptoms, no structural abnormality is present, so it is described as a functional disorder. People with these symptoms often have coexisting anxiety or depression, and there is a theory that the syndrome, a collection of symptoms, may be due to a disorder of brain-gut function.
This systematic review identified 53 randomised controlled trials. The review concluded that antidepressants are effective in reducing symptoms of irritable bowel syndrome, and there is evidence to suggest that psychological therapies also appear to be effective treatments, particularly where a therapist is directly involved.
Why was this study needed?
Irritable bowel syndrome is a problem for about 17% of people in the UK, and it affects more women than men. It can significantly affect the quality of life but is not associated with the development of serious disease or excess mortality. It is one of the most common conditions seen in general practice and gastroenterology clinics.
Psychiatric conditions including depression and anxiety often coexist with irritable bowel symptoms. It is thought that antidepressants may help people with irritable bowel syndrome because of effects on pain perception and gut motility. However, doubts on their effectiveness, conflicting evidence, concerns about side effects, and the stigma associated with psychiatric medication can result in physicians being reluctant to prescribe them.
This study aimed to update a previous meta-analysis with new data.
What did this study do?
This systematic review looked at the effects of antidepressants versus placebo in 17 trials and psychological therapies versus a control therapy or usual care (symptom monitoring, physician’s usual management, or supportive therapy) in 35 trials.
The trials took place in high income and upper middle-income countries with four from the UK. Antidepressants trials lasted between 4 to 12 weeks. Psychological therapy included cognitive behavioural therapy, relaxation training, hypnotherapy, mindfulness and stress management. One trial compared both psychological therapies and antidepressants with placebo.
There were no trials of psychological therapy at low risk of bias, because of the inability to blind participants to the treatment or control and the lack of clarity on whether medication was also used. The antidepressant trials were of higher quality with four having a low risk of bias. This reduces confidence in the findings, however is unlikely to account for the large effect in the antidepressant trials.
Because of the variation in patient-reported symptom scales used, the researchers chose to look at the number of people who had not improved on any scale, as the main outcome of interest.
What did it find?
- Irritable bowel symptoms improved for more people taking antidepressants than those taking a placebo. This was reported as a lack of improvement for 43.5% (266/612) of people taking antidepressants compared with 66.0% (340/515) of those on placebo (relative risk [RR] of symptoms not improving 0.66, (95% confidence interval [CI] 0.57 to 0.76; 18 trials). Results were similar for tricyclic antidepressants and serotonin reuptake inhibitors.
- Antidepressants had no effect on abdominal pain for 47.8% (87/182) of participants compared with 72.8% (123/169) of people taking placebo (RR of abdominal pain not improving 0.62, 95% CI 0.43 to 0.88; 7 trials).
- Side effects were common, affecting 36.4% (83/228) of participants on antidepressants compared with 21.1% (47/223) allocated to placebo (RR 1.56, 95% CI 1.23 to 1.98; 8 trials). Trials assessing the effect of tricyclics reported higher rates of side effects such as drowsiness and dry mouth.
- Irritable bowel symptoms improved for more people receiving psychological therapies than those cared for without them. This was reported as a lack of improvement in irritable bowel symptoms for 52.2% (735/1,407) of people receiving psychological therapies, compared with 75.9% (820/1,080) receiving control therapy (RR of symptoms not improving with psychological therapies was 0.69, 95% CI 0.62 to 0.76; 36 trials).
What does current guidance say on this issue?
The 2008 NICE guideline (updated 2017) on irritable bowel syndrome in adults recommends considering tricyclics as second-line treatment for people with irritable bowel syndrome if laxatives or medication to prevent muscle cramps (antispasmodics such as mebeverine) have not helped. Serotonin reuptake inhibitors should be considered only if tricyclics are ineffective. Follow up of people taking these drugs for the first time for the treatment of pain or discomfort is required after four weeks and then every 6 to 12 months.
Referral for psychological interventions such as talking therapy or hypnotherapy should be considered for people with irritable bowel syndrome who do not respond to pharmacological treatments after 12 months.
What are the implications?
This systematic review and meta-analysis demonstrate that antidepressants are probably effective treatments for irritable bowel syndrome. Adverse effects are more common with antidepressants, particularly tricyclics. Talking therapy also appears beneficial although there are inherent problems in evaluating these therapies.
Compared with previous reviews, the overall summary of effects has remained similar. This review also demonstrates that it is difficult to eliminate expectation bias in the assessment of psychological therapies.
Better patient stratification and studies looking into which groups of patients are more likely to respond to these therapies could help tailor treatments.
Citation and Funding
Ford AC, Lacy BE, Harris LA, Quigley EM, Moayyedi P. Effect of antidepressants and psychological therapies in irritable bowel syndrome: an updated systematic review and meta-analysis. Am J Gastroenterol. 2018; 3 Sep 3. doi:10.1038/s41395-018-0222-5. [E-pub].
This review was funded by the American College of Gastroenterology.
Khanbhai A and Sura DS. Irritable bowel syndrome for primary care physicians. BJMP. 2013;6(1):a608.
Thompson WG, Heaton KW, Smyth GT and Smyth C. Irritable bowel syndrome in general practice: prevalence, characteristics, and referral. Gut. 2000;46(1):78-82.
NICE. Irritable bowel syndrome in adults: diagnosis and management. CG61. London: National Institute for Health and Care Excellence. 2008 (updated 2017).
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