| |

Received: 28 March 2019    First decision: 25 April 2019    Accepted: 8 May 2019

DOI: 10.1111/apt.15325

Systematic review with meta‐analysis: the prevalence of

anxiety and depression in patients with irritable bowel
syndrome

Mohammad Zamani1,2  | Shaghayegh Alizadeh‐Tabari1  | Vahid Zamani3

1
Student Research Committee, School
of Medicine, Babol University of Medical
Sciences, Babol, Iran
2
Cancer Research Center, Health Research
Institute, Babol University of Medical
Sciences, Babol, Iran
3
Vice‐Chancellery for Health, Babol
University of Medical Sciences, Babol, Iran
Correspondence
Mohammad Zamani, School of Medicine,
Babol University of Medical Sciences,
Ganjafrooz Street, Babol, Mazandaran, Iran.
Email: mzamani20@gmail.com
Summary
Background: Irritable bowel syndrome (IBS) is a common and potential disabling func‐
tional gastrointestinal disorder. Studies have revealed a possible association between
IBS and psychological problems, such as anxiety and depression. Existing systematic
reviews have addressed only the levels of anxiety or depression in patients with IBS.
Aim: To investigate systematically the prevalence of anxiety or depression in IBS
patients
Methods: A literature search was conducted using the related keywords from the
bibliographic databases of Embase, PubMed, Scopus, Web of Science and POPLINE
published until 1 January 2019 with no language restriction. Studies reporting the
prevalence of anxiety/depressive symptoms/disorders in adult (≥15  years) IBS pa‐
tients were evaluated. The pooled prevalence, odds ratio (OR) and 95% CI were cal‐
culated using stata software.
Results: A total of 14 926 articles were initially screened, and finally 73 papers were
included. The prevalence rates of anxiety symptoms and disorders in IBS patients
were 39.1% (95% CI: 32.4‐45.8) and 23% (95% CI: 17.2‐28.8) respectively. The ORs
for anxiety symptoms and disorders in IBS patients compared with healthy subjects
were 3.11 (95% CI: 2.43‐3.98) and 2.52 (95% CI: 1.99‐3.20) respectively. The preva‐
lence estimates of depressive symptoms and disorders in IBS patients were 28.8%
(95% CI: 23.6‐34) and 23.3% (95% CI: 17.2‐29.4) respectively. The ORs for depres‐
sive symptoms and disorders in IBS patients compared to healthy subjects were 3.04
(95% CI: 2.37‐3.91) and 2.72 (95% CI: 2.45‐3.02) respectively.
Conclusion: Patients with IBS have a three‐fold increased odds of either anxiety or
depression, compared to healthy subjects.

As part of AP&T’s peer‐review process, a technical check of this meta‐analysis was

performed by Dr Y Yuan. The Handling Editor for this article was Dr Colin Howden, and it
was accepted for publication after full peer‐review.

Aliment Pharmacol Ther. 2019;00:1–12. © 2019 John Wiley & Sons Ltd |  1
wileyonlinelibrary.com/journal/apt  
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2       ZAMANI et al.
1 |  I NTRO D U C TI O N
Irritable bowel syndrome (IBS) is a prevalent, costly and potentially
disabling functional gastrointestinal disorder that presents with ab‐
dominal pain accompanied by constipation, diarrhoea and/or bloat‐
ing.1 The global prevalence of IBS has been estimated to be 11.2%,
but regionally it varies between 1.1% and 45% of the general popula‐
tion, 2 and can impose a major cost burden on the healthcare services
and society.3,4
The evidence show that IBS is associated with poor quality of life
and impaired social function, and some studies also allude to its as‐
sociation with psychological‐psychiatric conditions, such as anxiety
and depression. Major psychosocial problems have been reported
to be observed in 50%‐60% of IBS patients. 5,6
Some papers stated
that about 20%‐40% of IBS patients present with depressive symp‐
7
toms. Recent meta‐analyses showed that the levels of anxiety and
depression were significantly higher in IBS patients compared with
healthy controls, 7-9
but no meta‐analysis exists revealing the preva‐
lence rates of anxiety or depression in IBS patients compared with
controls. "Levels" of psychiatric comorbidities in IBS patients do not
provide clinical guidance, but only show that the "severity" of the
problem is higher or lower than controls. To facilitate early detection
and plan appropriate strategies for allocating health care resources
and better management of a disease, physicians need to be aware of
its "prevalence."
IBS patients who suffer from psychological comorbidities are
expected to be at high risk of personal suffering, impaired social
function, decreased treatment adherence, poor quality of life and
increased risk of suicidal behaviour. 10-12
Therefore, it should be
helpful to understand precisely the status of psychiatric problems
in patients with IBS. Considering that no systematic analysis exists
in this regard, we aimed to perform a comprehensive systematic re‐
view and meta‐analysis on the prevalence of anxiety and depression
in patients with IBS. In the next step, we tried to compare the data
between IBS patients and non‐IBS healthy controls to assess any po‐
tential association between the psychiatric problems and IBS. These
data should help better understand and manage patients with IBS,
and its psychological comorbidities.
2 |  M ATE R I A L S A N D M E TH O DS
2.1 | Information sources and search strategy
A literature search was conducted from the bibliographic databases
of Embase, PubMed, Scopus, Web of Science and POPLINE pub‐
lished from the inception to 1 January 2019 with no language re‐
striction. The related terms were searched in the Medical Subject
Headings (MeSH) database, and finally, the keywords included "anxi‐
ety" OR "anxieties" OR "depression" OR "depressive" OR "depres‐
sions" OR "emotional" OR "emotion" OR "mental" OR "psychiatry"
OR "psychology" OR "psychological" OR "psychiatric" AND "Irritable
Bowel Syndrome" OR "IBS." The search was limited to Title/Abstract.
Reference lists of the related reviews and the retrieved papers were
manually searched for additional sources.
The present systematic review and meta‐analysis was conducted
according to the PRISMA (Preferred reporting items for systematic
review and meta‐analysis) guideline.13 The preplanned protocol
of our study was documented online in the PROSPERO registry
(CRD42018108512).14
2.2 | Inclusion and exclusion criteria
We included studies reporting the prevalence of anxiety/depressive
symptoms/disorders in patients with IBS. To be eligible for inclusion
in the analysis, every study had to recruit at least 100 adults (aged
≥15  years old). IBS patients could be diagnosed by questionnaire,
Manning criteria, Rome criteria, and/or International Classification
of Diseases (ICD) codes. Anxiety/depression should be diagnosed by
validated methods and instruments ("symptoms" by questionnaires;
"disorders" by a structured psychiatric interview, ICD codes, etc).
The exclusion criteria were as follows:
1. Reviews, case reports, editorials, letter to the editors and ab‐
stracts from conferences.
2. Duplicate articles or evaluating the same sample.
3. Studies on IBS patients with concomitant diseases (eg, morbid
obesity, surgery, inflammatory bowel disease, etc).
4. Studies on patients with post‐infectious IBS.
5. Studies with sample size of <100 subjects.
6. Studies recruited children.
7. Surveys without clear methodology or results.
8. Full‐texts not being available.
2.3 | Study selection and data extraction
Two reviewers (MZ, VZ) screened independently the titles and ab‐
stracts of all references for potential suitability. Full‐texts of the
potential articles were obtained for the final assessment of suit‐
ability for inclusion. Any discrepancies pertaining to the inclusion
of articles were resolved by consensus between the authors. Data
were assessed and extracted from the studies by two authors
(MZ, SA) and finally included for analysis into a Microsoft Excel
spreadsheet (Microsoft Corporation, Redmond, Washington). The
following data were extracted: first author's name, study location
(country), publication date, diagnostic method of IBS, diagnostic
method of anxiety/depression, total sample size, number of sub‐
jects by gender (if available), number of different IBS‐subgroup
patients (constipation‐predominant IBS [IBS‐C], diarrhoea‐pre‐
dominant IBS [IBS‐D], mixed IBS [IBS‐M], and undefined IBS
[IBS‐U], if available), number of healthy control subjects (if avail‐
able), prevalence rates of anxiety/depressive symptoms/disorders.
Healthy controls included the subjects who did not suffer from any
functional gastrointestinal disorders, and therefore, we excluded
ZAMANI et al.
the data on the controls who did not have IBS but had other func‐
tional gastrointestinal disorders.
Google Translate was used to translate non‐English reports.
When a study used different diagnostic instruments for IBS and/or
anxiety/depression, we considered each one of the primary analyses
as a separate report. If full‐texts and/or necessary data of articles
were not available, we contacted the corresponding authors by email
to send us the information. We excluded duplicates and only selected
those with the most comprehensive details. When prevalence rates
of anxiety/depressive symptoms were not obviously reported in the
papers text (for example, when the symptoms were presented as se‐
verity categories based on questionnaire scores), we calculated them
using the cut‐off for the significantly elevated symptoms reported
by the authors based on references. In addition, if the prevalence
rates were reported at different time points, we used only the data
of the first evaluation. For the present study, we considered anxiety/
depressive "symptoms" and anxiety/depressive "disorders" as two
separate outcomes. In mental health care, there is a distinction be‐
tween "symptoms" and "disorders." The symptoms in the "disorders"
are more severe and are associated with impairment in life. Besides,
"symptoms" are usually measured by a questionnaire, whereas "disor‐
ders" are diagnosed using the criteria of the Diagnostic and Statistical
Manual of Mental Disorders in a psychiatric interview.15
2.4 | Risk of bias assessment
For assessing quality of the included studies, the checklist by Hoy
16
et al was used. It has been designed for the prevalence studies
and has nine criteria with two potential responses, including Yes
(score 0, low risk) or No (score 1, high risk). The nine criteria were
related to target population, sampling frame, selection of sample,
response rate by subjects, how to data collection, case definition,
study instrument, same mode of data collection, and numerators
and dominators for the parameters. The minimum and maximum
scores are 0 and 9. Studies with higher scores had higher risk of
bias and lower quality.
2.5 | Study outcomes and statistical analysis
The data extracted from the retrieved articles were combined to give
the pooled prevalence rates using the Inverse Variance models (in‐
cluding a double arcsine transformation). The pooled prevalence rates
were presented as percent and 95% CI. The heterogeneity between
the studies was evaluated using the I2 statistic with a cut‐off of 50%,
and the chi‐squared test with a P  <  0.10, used to define a statisti‐
17
cally significant degree of heterogeneity. Publication bias was as‐
sessed using a funnel plot and Egger's test. Data were pooled by using
a random‐effects model18 to give a more conservative estimate of the
prevalence rate of anxiety/depressive symptoms/disorders and the
odds ratio (OR) of the symptoms/disorders in IBS patients and healthy
subjects. Meta‐regression was used to explore potential influence of
gender (% male) and publication year on the outcomes, and P < 0.05
was considered statistically significant. Subgroup analyses were
|
      3
performed according to IBS subgroup (IBS‐C, IBS‐D, IBS‐M), gender
(male and female) and IBS diagnostic instrument (Rome I, II and III).
A subgroup difference of P  <  0.05 was considered to be indicative
of significant difference between subgroups. All statistical analyses
were done using stata (StataCorp, College Station, TX).
3 | R E S U LT S
3.1 | Search results, study selection and
characteristics
The initial search in the databases identified a total of 14 926 cita‐
tions and 5847 remained after removing duplicates. After evaluat‐
ing the title and/or abstract, 5634 articles were excluded because
of failure to meet the inclusion criteria. Full‐text of the remain‐
ing 213 papers was assessed for eligibility; 73 eligible articles
were included in the final analyses. The results of search strategy
are shown in a flow diagram according to the PRISMA guideline
(Figure 1). The characteristics of the included articles are summa‐
rised in Tables S1‐S4.
3.2 | Anxiety symptoms
The information of studies related to anxiety symptoms have been
summarised in Table S1. Analysis of 43 articles19-61 indicated that
the pooled prevalence of anxiety symptoms was 39.1% (95% CI:
32.4‐45.8; I2  =  99.1%) in 16  572 IBS patients (Figure 2). Visual in‐
spection of the funnel plot shows some asymmetry (Figure S1).
Egger's test also indicated significant publication bias (P  =  0.010).
Meta‐regression analyses indicated that gender (% male, β = 0.002,
P = 0.810) and publication year (β = 0.045, P = 0.070) did not explain
the heterogeneity in outcomes.
Subanalysis exhibited that the pooled OR for anxiety symp‐
toms in IBS patients compared with healthy subjects was 3.11 (95%
CI: 2.43‐3.98) based on 24 papers, with significant heterogeneity
between studies (I2 = 93.6%, P < 0.001) (Figure S2). Subgroup anal‐
yses from five studies showed that the pooled prevalence rates of
anxiety symptoms were 43.7% (95% CI: 33.2‐54.2), 35.5% (95%
CI: 26.9‐44.1) and 37% (95% CI: 26.9‐47) in patients with IBS‐C,
IBS‐D and IBS‐M respectively. Subgroup analyses by gender from
five articles on males and eight papers on females showed that
the pooled prevalence of anxiety symptoms was 31.5% (95% CI:
15.3‐47.7) and 47.8% (95% CI: 36‐59.6) in males and females with
IBS respectively. The pooled OR for anxiety symptoms in male
IBS patients compared with female IBS patients was 0.47 (95% CI:
0.18‐1.23) based on five studies, with significant heterogeneity
between studies (I 2  =  93.4%, P  <  0.001). Regarding IBS diagnos‐
tic instruments, 4, 15 and 21 studies used Rome I, Rome II and
Rome III, and the subgroup analysis by these criteria showed the
pooled prevalence rates of 36.5% (95% CI: 14.5‐58.5), 41.3% (95%
CI: 31.6‐51.1) and 43.5% (95% CI: 31.3‐55.7) for anxiety symptoms
respectively (P = 0.558). No enough data existed to perform sub‐
group analysis by other diagnostic methods.
 |
4       ZAMANI et al.

Records identified thorugh database searching

(n = 14 926)
• Emabse: 4306
Identification

• PubMed: 2717
Additional record identified
• Scopus: 3233 through other sources
(n = 1)
• Web of Science: 4648
• POPLINE: 22

Records after duplicates removed

(n = 5847)
Screening

Records screened for title Records excluded

and abstract (n = 5634)
(n = 5847)

Full-text artciles excluded, with

reasons (n = 140):

Full-text articles assessed

Eligibility

for eligibility • The same data (n = 6)

(n = 213)
• Less than 100 patients (n = 21)
• No valid diagnostic method (n = 8)
• Pateints with specific disease (n = 1)
• Full-text not available (n = 23)
• Lack of clear methodology or results
(n = 81)
Included

73 articles included

F I G U R E 1   PRISMA flow diagram

(I2 = 97.3%, P < 0.001) (Figure S4). No enough data existed to per‐

3.3 | Anxiety disorders
The information of studies related to anxiety disorders have been
summarised in Table S2. The pooled prevalence of anxiety disorders
was 23% (95% CI: 17.2‐28.8; I2 = 99.9%) among 375 534 IBS patients
based on 20 articles51,62-80 (Figure 3). Visual inspection of the fun‐
nel plot did not indicate any potential publication bias (Figure S3).
Egger's test also showed no significant evidence of publication bias
among the included studies (P  =  0.478). Meta‐regression analyses
indicated that gender (% male, β −= −0.010, P = 0.157) and publica‐
tion year (β  =  0.001, P  =  0.981) did not explain the heterogeneity
between studies.
Analysis of nine studies showed that the pooled OR for anxiety
disorders in IBS patients compared with healthy subjects was 2.52
(95% CI: 1.99‐3.20), with significant heterogeneity between studies
form subgroup analysis by gender and IBS subgroup.
3.4 | Depressive symptoms
The information of studies related to depressive symptoms has been
summarised in Table S3. Analysis of 47 articles19-42,44-46,48-61,81-86
indicated that the pooled prevalence of depressive symptoms
was 28.8% (95% CI: 23.6‐34; I2  =  99.1%) in 22  842 IBS patients
(Figure 4). Visual inspection of the funnel plot indicates some asym‐
metry (Figure S5). However, Egger's test showed no significant evi‐
dence of publication bias among the included studies (P  =  0.517).
Meta‐regression analyses indicated that gender (% male, β =−0.016,
P = 0.108) and publication year (β = −0.028, P = 0.265) did not ex‐
plain the heterogeneity in outcomes.
ZAMANI et al. |
      5

Study %
ID Prevalence (95% CI) Weight

Afridi (2017) 37.70 (31.34, 44.06) 2.03

Aziz (2015) 28.00 (19.90, 36.10) 2.01
Ballou (2016) 60.00 (52.82, 67.18) 2.02
Baysoy (2014 (A)) 57.50 (50.97, 64.03) 2.03
Baysoy (2014 (B)) 67.90 (61.73, 74.07) 2.04
Bengtson (2015) 28.30 (23.48, 33.12) 2.05
Björkman (2015) 21.00 (17.62, 24.38) 2.06
Bruno (2018) 87.40 (81.23, 93.57) 2.04
Cho (2011) 38.60 (30.03, 47.17) 2.00
Choi (2010) 49.60 (43.58, 55.62) 2.04
Dong (2010) 23.40 (16.98, 29.82) 2.03
Drossman (1988) 8.40 (4.02, 12.78) 2.05
Fan (2017) 43.80 (39.52, 48.08) 2.05
Faresjö (2007) 25.10 (20.54, 29.66) 2.05
Ford (2014) 32.80 (29.98, 35.62) 2.06
Fysekidis (2018) 8.20 (5.20, 11.20) 2.06
Fysekidis (2018) 3.10 (1.21, 4.99) 2.07
Graham (2010) 75.20 (67.24, 83.16) 2.01
Hillilä (2004 (A)) 39.00 (35.05, 42.95) 2.06
Hillilä (2004 (B)) 39.40 (34.30, 44.50) 2.05
Hillilä (2004 (C)) 45.10 (38.27, 51.93) 2.03
Hillilä (2004 (D)) 41.80 (34.67, 48.93) 2.02
Ibrahim (2013) 44.20 (37.14, 51.26) 2.03
Iorio (2014) 73.20 (71.12, 75.28) 2.07
Jamali (2015) 73.00 (67.50, 78.50) 2.04
Jerndal (2010) 26.00 (21.09, 30.91) 2.05
Kanuri (2016) 31.30 (25.79, 36.81) 2.04
Kennedy (2006) 52.30 (44.28, 60.32) 2.01
Longstreth (2005) 33.00 (25.48, 40.52) 2.02
Longstreth (2001) 39.20 (33.09, 45.31) 2.04
Mansouri (2017) 30.80 (26.27, 35.33) 2.05
Mearin (2006) 26.50 (22.70, 30.30) 2.06
Miller (2015) 63.40 (60.41, 66.39) 2.06
Miller (2004) 46.90 (41.25, 52.55) 2.04
Naeem (2012) 55.80 (46.16, 65.44) 1.99
Nam (2013) 11.60 (7.69, 15.51) 2.06
Okami (2011) 39.80 (35.97, 43.63) 2.06
Patel (2015) 33.90 (30.66, 37.14) 2.06
Pohl (2018) 43.20 (33.98, 52.42) 1.99
Riddle (2016) 9.60 (6.34, 12.86) 2.06
Simrén (2001) 10.00 (6.76, 13.24) 2.06
Singh (2012) 74.50 (68.20, 80.80) 2.04
Son (2008) 53.80 (44.22, 63.38) 1.99
Spiller (2010) 72.40 (67.49, 77.31) 2.05
Thijssen (2010) 30.40 (24.46, 36.34) 2.04
Uz (2007) 10.00 (4.12, 15.88) 2.04
Vandvik (2004) 19.20 (13.85, 24.55) 2.05
Vork (2017) 35.60 (30.93, 40.27) 2.05
Wilpart (2017) 17.20 (12.52, 21.88) 2.05
Overall (I-squared = 99.1%, P = 0.000) 39.07 (32.35, 45.79) 100.00
NOTE: Weights are from random effects analysis

–93.6 0 93.6

F I G U R E 2   Pooled prevalence of anxiety symptoms in patients with the irritable bowel syndrome

Sub‐analysis exhibited that the pooled OR for depressive symp‐ analyses from five studies showed that the pooled prevalence rates
toms in IBS patients compared with healthy subjects was 3.04 (95% of depressive symptoms were 41.4% (95% CI: 20.2‐62.8), 37.1% (95%
CI: 2.37‐3.91) based on 24 papers, with significant heterogene‐ CI: 16.7‐57.6) and 36.8% (95% CI: 17.3‐56.4) in patients with IBS‐C,
ity between studies (I2  =  93.8%, P  <  0.001) (Figure S6). Subgroup IBS‐D and IBS‐M respectively. Subgroup analyses by gender from
 |
6       ZAMANI et al.

Study %
ID Prevalence (95% CI) Weight

Blanchard (2001) 38.70 (33.53, 43.87) 5.03

Clevers (2018) 5.90 (5.51, 6.29) 5.24
Creed (2005) 25.30 (19.99, 30.61) 5.02
Grzesiak (2014) 47.20 (37.70, 56.70) 4.60
Guthrie (2003) 29.90 (21.23, 38.57) 4.70
Guthrie (1991) 18.00 (10.54, 25.46) 4.83
Guthrie (1993) 22.60 (14.48, 30.72) 4.76
Hyphantis (2009) 25.90 (20.44, 31.36) 5.01
Janssens (2015) 14.70 (13.96, 15.44) 5.24
Kawoos (2017) 31.90 (24.68, 39.12) 4.85
Lacy (2019) 17.60 (17.43, 17.77) 5.24
Ladabaum (2012) 36.40 (36.15, 36.65) 5.24
Lee (2009) 16.50 (9.53, 23.47) 4.88
Lee (2015) 4.40 (3.81, 4.99) 5.24
Lix (2010) 34.40 (26.85, 41.95) 4.82
Modabbernia (2012) 34.80 (28.96, 40.64) 4.98
Riddle (2016) 8.30 (5.25, 11.35) 5.17
Stasi (2018) 20.10 (13.69, 26.51) 4.93
Talley (2001) 10.60 (4.92, 16.28) 4.99
Whitehead (2007) 21.60 (20.16, 23.04) 5.23
Overall (I-squared = 99.9%, P = 0.000) 23.00 (17.18, 28.82) 100.00

NOTE: Weights are from random effects analysis

–56.7 0 56.7

F I G U R E 3   Pooled prevalence of anxiety disorders in patients with the irritable bowel syndrome

seven articles on males and nine papers in females showed that
the pooled prevalence of depressive symptoms was 25.9% (95% CI:
11.9‐39.9) and 35.1% (95% CI: 23‐47.3) in males and females with
IBS respectively. The pooled OR for anxiety symptoms in male
IBS patients compared with female IBS patients was 0.84 (95% CI:
0.64‐1.11) based on seven studies, with significant heterogeneity
between studies (I2 = 55.1%, P = 0.037). In relation to IBS diagnostic
instruments, 4, 16 and 23 studies used Rome I, Rome II and Rome III,
and the subgroup analysis by these criteria showed the pooled prev‐
alence rates of 18.5% (95% CI: 7.5‐29.5), 30.9% (95% CI: 23.5‐38.3)
and 32.2% (95% CI: 23.1‐41.3) for depressive symptoms respectively
(P = 0.046). No enough data existed to perform subgroup analysis by
other diagnostic methods.
(95% CI: 17.2‐29.4; I2  =  99.9%) in 407,967 IBS patients (Figure 5).
Visual inspection of the funnel plot did not indicate any potential
publication bias (Figure S7). Egger's test also showed no significant
evidence of publication bias among the included studies (P = 0.388).
Meta‐regression analyses indicated that gender (% male, β = −0.002,
P = 0.769) and publication year (β =− 0.017, P = 0.494) did not explain
the heterogeneity between studies.
Analysis of 10 papers indicated that the pooled OR for depres‐
sive disorders in IBS patients compared with healthy subjects was
2.72 (95% CI: 2.45‐3.02), with significant heterogeneity between
studies (I2 = 92.8%, P < 0.001) (Figure S8). No enough data existed to
perform subgroup analysis by gender and IBS subgroup.

3.5 | Depressive disorders
The information of studies related to depressive disorders
has been summarised in Table S4. Pooling data from 19 arti‐
cles62,63,66,67,69-73,75,77-80,87-91 showed a prevalence rate of 23.3%
4 | D I S CU S S I O N
In this study, we found considerable prevalence rates of anxiety and
depressive symptoms and disorders in IBS patients. It was also shown
that the risk of the mentioned psychiatric problems is significantly
ZAMANI et al.       7|
Study %
ID Prevalence (95% CI) Weight

Aziz (2015) 7.60 (2.82, 12.38) 2.01

Ballou (2016) 49.00 (41.68, 56.32) 1.96
Baysoy (2014) 12.30 (7.96, 16.64) 2.01
Bengtson (2015) 30.40 (25.48, 35.32) 2.01
Björkman (2015) 8.00 (5.75, 10.25) 2.03
Bruno (2018) 87.40 (81.23, 93.57) 1.98
Cho (2011) 38.60 (30.03, 47.17) 1.93
Choi (2010) 38.50 (32.64, 44.36) 1.99
Dong (2010) 25.10 (18.52, 31.68) 1.98
Drossman (1988) 18.20 (12.11, 24.29) 1.99
Fan (2017) 20.30 (16.83, 23.77) 2.02
Faresjö (2007) 6.10 (3.58, 8.62) 2.03
Ford (2014) 14.10 (12.01, 16.19) 2.04
Fysekidis (2018) 48.00 (42.54, 53.46) 2.00
Graham (2010) 64.60 (55.78, 73.42) 1.93
Hillilä (2004 (A)) 29.80 (26.10, 33.50) 2.02
Hillilä (2004 (B)) 34.00 (29.06, 38.94) 2.00
Hillilä (2004 (C)) 41.20 (34.45, 47.95) 1.97
Hillilä (2004 (D)) 38.00 (30.99, 45.01) 1.97
Ibrahim (2013) 18.90 (13.33, 24.47) 2.00
Iorio (2014) 73.20 (71.12, 75.28) 2.04
Jamali (2015) 57.00 (50.86, 63.14) 1.99
Jerndal (2010) 8.00 (4.96, 11.04) 2.03
Kanuri (2016) 21.70 (16.80, 26.60) 2.01
Kennedy (2006) 10.10 (5.26, 14.94) 2.01
Lackner (2013) 19.00 (13.98, 24.02) 2.00
Lee (2017) 44.90 (39.86, 49.94) 2.00
Lee (2015) 12.80 (11.92, 13.68) 2.04
Longstreth (2005) 13.00 (7.62, 18.38) 2.00
Longstreth (2001) 13.90 (9.57, 18.23) 2.01
Mearin (2006) 26.50 (22.70, 30.30) 2.02
Miller (2015) 25.50 (22.80, 28.20) 2.03
Miller (2004) 21.50 (16.85, 26.15) 2.01
Nam (2013) 9.30 (5.76, 12.84) 2.02
Okami (2011) 24.70 (21.33, 28.07) 2.02
Patel (2015) 13.20 (10.87, 15.53) 2.03
Pohl (2018) 14.40 (7.87, 20.93) 1.98
Riddle (2016) 8.00 (5.00, 11.00) 2.03
Roohafza (2016) 45.30 (42.25, 48.35) 2.03
Schauer (2018) 37.20 (29.41, 44.99) 1.95
Simrén (2001) 10.00 (6.76, 13.24) 2.03
Singh (2012) 64.10 (57.17, 71.03) 1.97
Son (2008) 76.00 (67.79, 84.21) 1.94
Spiller (2010) 36.10 (30.83, 41.37) 2.00
Teoman (2016) 21.60 (15.81, 27.39) 1.99
Thijssen (2010) 21.70 (16.37, 27.03) 2.00
Uz (2007) 38.00 (28.49, 47.51) 1.91
Vandvik (2004) 26.40 (20.41, 32.39) 1.99
Vork (2017) 18.80 (14.99, 22.61) 2.02
Wilpart (2017) 6.80 (3.68, 9.92) 2.03
Overall (I-squared = 99.1%, P = 0.000) 28.82 (23.63, 34.01) 100.00
NOTE: Weights are from random effects analysis

–93.6 0 93.6

F I G U R E 4   Pooled prevalence of depressive symptoms in patients with the irritable bowel syndrome

higher in IBS patients in comparison with healthy control subjects. To Recent meta‐analyses evaluated the levels, but not prevalence rates,
the best of our knowledge, this was the first comprehensive systematic of anxiety and depression in IBS patients and healthy controls by
review and meta‐analysis assessing the prevalence of anxiety or de‐ comparing the standardized mean difference (SMD) of the levels be‐
pression in IBS patients, and comparing the data with healthy subjects. tween the two groups. The meta‐analysis by Fond et al8 on 10 studies
 |
8       ZAMANI et al.

Study %
ID Prevalence (95% CI) Weight

Blanchard (2001) 7.00 (4.29, 9.71) 5.39

Chen (2016) 8.80 (8.49, 9.11) 5.45
Clevers (2018) 24.10 (23.38, 24.82) 5.45
Creed (2005) 28.80 (23.26, 34.34) 5.21
Guthrie (2003) 26.20 (17.87, 34.53) 4.94
Guthrie (1991) 30.00 (21.11, 38.89) 4.88
Hyphantis (2009) 29.60 (23.91, 35.29) 5.20
Janssens (2015) 6.10 (5.60, 6.60) 5.45
Kawoos (2017) 27.50 (20.58, 34.42) 5.09
Lackner (2014) 22.00 (15.86, 28.14) 5.16
Lacy (2019) 20.10 (19.92, 20.28) 5.45
Ladabaum (2012) 39.00 (38.75, 39.25) 5.45
Ladep (2006) 56.80 (48.35, 65.25) 4.93
Lee (2015) 5.10 (4.47, 5.73) 5.45
Modabbernia (2012) 16.00 (11.51, 20.49) 5.29
Stasi (2018) 14.70 (9.03, 20.37) 5.20
Talley (2001) 8.80 (3.58, 14.02) 5.24
Whitehead (2007) 30.50 (28.89, 32.11) 5.43
Wojczynski (2007) 45.00 (41.06, 48.94) 5.33
Overall (I-squared = 99.9%, P = 0.000) 23.26 (17.18, 29.35) 100.00

NOTE: Weights are from random effects analysis

–65.3 0 65.3

F I G U R E 5   Pooled prevalence of depressive disorders in patients with the irritable bowel syndrome

revealed significant higher levels of anxiety (pooled SMD = 0.76) and
depression (pooled SMD  =  0.80) in IBS patients versus controls. A
newer systematic review by Lee et al,9 which included 27 studies,
similarly indicated that the levels of anxiety (pooled SMD = 0.84) and
depression (pooled SMD = 0.76) were significantly higher in IBS pa‐
7
tients than in healthy controls. A review by Zhang et al performed on
24 comparative studies indicated that depressive symptoms are sig‐
nificantly more severe (SMD = 2.02) and more frequent (OR = 9.21) in
IBS patients compared with controls. The results retrieved by us and
other authors are in agreement with the theory that patients with IBS
are associated with degrees of anxiety and depression.
The explanation of the relationship between IBS and psychiat‐
ric comorbidities is probably related to the "brain‐gut" interactions.
Psychophysiological and neuroimaging studies have stated that
dysfunction of brain‐gut axis, which is a bidirectional neurological
connecting pathway between brain and digestive system, leads to
presentation of IBS. According to this model, abdominal symptoms
influence anxiety and depression, and on the other hand, the psy‐
chological factors physiologically increase risk of IBS symptoms.92,93
It is not difficult to accept that chronic IBS symptoms can have a
destabilising impact on quality of life, and be associated with stress,
work impairment and cost, and these factors aggravate mental disor‐
ders. Considering these theories and the results supporting the pos‐
itive relationship of IBS with the psychiatric problems, it can also be
hypothesised that treatment of IBS symptoms in the patients with
anxiety and depression can improve their psychiatric symptoms as
well. It is recommended that these comorbidities be systematically
checked and treated in IBS patients. Also, it is recommended that the
physicians treating the patients with anxiety and depression, assess
them in terms of IBS as well. If the co‐existence gastrointestinal dis‐
order diagnosed and treated, it would speed up improvement of the
psychiatric comorbidities too. Several published systematic reviews
summarised the efficacy of antidepressants and psychological ther‐
apies in patients with IBS.94,95
Subgroup analysis in the present study showed that patients
IBS‐C type had highest prevalence rates of both anxiety and de‐
pressive symptoms. Although the number of papers representing
the data related to different IBS subgroups were few, we are able to
somewhat explain the results and compare them with other studies.
There are different reports about which IBS type is more associated
ZAMANI et al.
with anxiety and depression than other types. In the meta‐analysis
9
by Lee et al, IBS‐C patients indicated the highest SMD for anxiety
and depression, and it was explained that this is probably due to an
imbalance of 5‐hydroxytryptamine (5‐HT) secretion, leading to con‐
stipation in these patients. 5‐HT belongs to the intestinal serotonin
system helping better gastrointestinal motility, which is also present
in the central nervous system as a neurotransmitter contributing in
mental health.96,97 So, it is probable that the low responsiveness of
5‐HT in both of the central and peripheral regions lead to the psychi‐
atric problems in IBS‐C patients. However, all types of IBS had high
prevalence of anxiety and depression in our study.
According to the results, anxiety and depressive symptoms were
not more prevalent in females than in males. Generally, females are
more prone to worse mental health than males.98,99 This is related
to inner and outer factors. Inner factors are mainly related to hor‐
monal effects. Oestrogen and progesterone are involved in stabil‐
ity of mental health and fluctuations in their level over the females'
life, like puberty, menstrual cycle, pregnancy and menopause, can
trigger changes in their mental health. Environmental factors are
also linked to females' mental health.100-102 Lower social power and
higher stress lead females to be more prone to mental disorders.99
However, more studies are suggested to investigate the gender dif‐
ferences in depression and anxiety among IBS patients.
A limitation of this systematic review pertains to the high hetero‐
geneity between the studies. According to meta‐regression, gender
(% male) and publication year cannot justify the heterogeneity. The
high heterogeneity could be probably due to differences in study
place and/or diagnostic methods for IBS and the psychiatric comor‐
bidities. Publication bias assessment did not show significant bias
among the studies on anxiety and depressive disorders or symp‐
toms, therefore, heterogeneity between studies may not be due
to publication or reporting bias, but to other factors. On the other
hand, there was a significant publication bias for anxiety symptom
studies, hence, heterogeneity may be due to publication or reporting
bias. Prevalence of anxiety and depression can vary according to the
cultural region, which can result from actual differences in preva‐
lence and discrepancies in measurement (due to translation, and lim‐
ited validation of questionnaires).9 Variations in cut‐offs of elevated
symptoms for the same instruments were other potential reason of
heterogeneity. Altogether, such high heterogeneity in prevalence
meta‐analyses is not unexpected.103 However, the results of the
present study should be interpreted with caution.
The main strong point of this study is the wide range of reports,
and the large total number of patients analysed. The selected studies
relate to control groups of healthy subjects, without reported IBS.
4.1 | Conclusions
This systematic review and meta‐analysis shows that the preva‐
lence of anxiety or depressive symptoms and disorders are con‐
siderable in IBS patients. In addition, we found that IBS patients
are more at risk of the given psychiatric comorbidities compared
with control subjects. It is recommended that gastroenterologists
|
      9
and other physicians, who are responsible for treatment of IBS
patients, pay attention to and assess the concurrent presence of
anxiety or depression in the patients as well, and consider special‐
ist treatment for the psychiatric disorder. Also, it is recommended
that those physicians treating patients with anxiety and depres‐
sion also assess them in terms of IBS as well. If the co‐existence
gastrointestinal disorder is diagnosed and treated, it could also
speed the improvement of the psychiatric comorbidities.
AC K N OW L E D G E M E N T S
We are thankful to Prof. Alexander C Ford, Dr. Sun‐Young Lee, Dr.
Yu Tien Wang, Dr. Egbert Clevers, Dr. Parnaz Daneshpajouhnejad,
Mr. Ewan Donnachie, Dr. Motoyori Kanazawa, Dr. Gökhan Baysoy,
Dr. Yukiko Okami, Dr. Akane Higashi, Dr. Michel Bouchoucha, Dr.
Mohammad Biglari, Dr. Roger Jones, Dr. Paul Seed, Dr. Douglas A
Drossman, Dr. Marianne Bonnert and Prof. Robin Spiller for answer‐
ing our queries about their studies. We would also like to thank the
Vice Chancellor for Research and Technology of Babol University of
Medical Sciences for supporting our study.
Declaration of personal interests: None.
AU T H O R S H I P
Guarantor of the article: None.
Author contributions: MZ contributed to study design. MZ, SAT
and VZ involved in data collection. MZ contributed to data analysis.
MZ, SAT and VZ drafted the manuscript. All authors have read the
manuscript and approved its final version.
ORCID
Mohammad Zamani  https://orcid.org/0000-0003-1916-3873
Shaghayegh Alizadeh‐Tabari  https://orcid.org/0000-0002-1922-4114
Vahid Zamani  https://orcid.org/0000-0001-7485-1842
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information will be found online in the
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How to cite this article: Zamani M, Alizadeh‐Tabari S, Zamani
V. Systematic review with meta‐analysis: the prevalence of
anxiety and depression in patients with irritable bowel
syndrome. Aliment Pharmacol Ther. 2019;00:1–12. https​://doi.
org/10.1111/apt.15325​