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NIHR Signal Treatments for depression may help irritable bowel symptoms

Published on 12 February 2019

doi: 10.3310/signal-000732

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.

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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.

Bibliography

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).

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.

Bibliography

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).

Effect of Antidepressants and Psychological Therapies in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-analysis

Published on 5 September 2018

Ford, A. C.,Lacy, B. E.,Harris, L. A.,Quigley, E. M.,Moayyedi, P.

Am J Gastroenterol , 2018

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain-gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective. METHODS: We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or "usual management" were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). RESULTS: The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or "usual management", and one compared both psychological therapy and antidepressants with placebo. Four of the trials of psychological therapies, and one of the RCTs of antidepressants, were identified since our previous meta-analysis. The RR of IBS symptoms not improving with antidepressants versus placebo was 0.66 (95% CI 0.57-0.76), with similar treatment effects for both tricyclic antidepressants and SSRIs, although with heterogeneity between RCTs of the latter (I(2) = 49%, P = 0.07). The RR of symptoms not improving with psychological therapies was 0.69 (95% CI 0.62-0.76). Cognitive behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled. There was significant heterogeneity between studies (I(2) = 69%, P < 0.001) and significant funnel plot asymmetry. There were also issues regarding trial design, including lack of blinding. CONCLUSIONS: Antidepressants are efficacious in reducing symptoms in IBS patients. Psychological therapies also appear to be effective treatments for IBS, although there are limitations in the quality of the evidence, and treatment effects may be overestimated as a result.

Expert commentary

This meta-analysis affirms the role of both antidepressants and psychological therapies in irritable bowel syndrome.

The efficacy of tricyclics and serotonin reuptake inhibitors in improving global symptom scores is substantiated. However, the potentially harmful effects of these drugs, particularly tricyclics, which may cause dry mouth and drowsiness, is confirmed. This perhaps explains why they are not more widely used by patients and physicians.

Eliminating bias in the assessment of psychological therapies is difficult; patients know which therapy they receive, but CBT, multi-component, relaxation therapy and dynamic psychotherapy, appear effective. Furthermore, adverse events are infrequently reported in clinical practice. It remains to be seen whether more remote interventions are less effective or whether the existing trials are simply not large enough to demonstrate statistical significance.

Simon Smale, Gastroenterologist, Manchester University NHS Foundation Trust

The commentator is a trustee and acting Chair of the IBS Network, and a shareholder and CEO of More Than Just Medicine Ltd

Expert commentary

This review suggests that antidepressants and a variety of different psychological treatments are equally helpful for irritable bowel syndrome. Most studies were carried out in secondary care, so the findings are most relevant for people with persistent symptoms. Further high-quality studies are required particularly to evaluate psychological treatment.

Antidepressants have direct effects on the gut, in addition to their effects on mood. Psychological treatments help people to manage their symptoms better and tackle emotional problems which are interfering with recovery. The findings suggest that there should be a greater choice of psychological treatments available for sufferers.

Else Guthrie, Professor of Psychological Medicine, University of Leeds

The commentator declares collaboration with the corresponding author of this review on other work