ORIGINAL ARTICLES

Do Antidepressants Influence the Disease Course in

Inflammatory Bowel Disease? A Retrospective
Case-matched Observational Study
J.R. Goodhand, MRCP, F.I.S. Greig, MBBS, Y. Koodun, BSc, A. McDermott, M. Wahed, MBBS,
L. Langmead, MRCP, MD, and D.S. Rampton, FRCP, DPhil

Background: Depression, like adverse events and psychological stress, can trigger relapse in inflammatory bowel disease (IBD); however, the
effects of psychoactive drugs on disease course are unclear.
Methods: Using retrospective electronic case note review, after exclusion of five patients on low-dose tricyclic antidepressants we compared
the course of IBD in 29 patients (14 ulcerative colitis and 15 Crohn’s disease), during the years before (year 1) and after (year 2) they were
started on an antidepressant for a concomitant mood disorder to that of controls matched for age, sex, disease type, medication at baseline, and
relapse rate in year 1.
Results: Patients had fewer relapses and courses of steroids in the year after starting an antidepressant than in the year before (1 [0–4] (median
[range]) vs. 0 [0–4], P ¼ 0.002; 1 [0–3] vs. 0 [0–4], P < 0.001, respectively); the controls showed no changes between years 1 and 2 in relapses
(1 [0–4] vs. 1 [0–3], respectively) or courses of steroids (1 [0–2] vs. 0 [0–3]). Although there were no differences in the use of other relapse-
related medications, outpatient attendances, or hospital admissions, the number of endoscopies fell significantly in the antidepressant group in
year 2 compared with year 1 (P < 0.01). No such changes were seen in the controls.
Conclusions: Antidepressants, when used to treat concomitant mood disorders in IBD, seem to reduce relapse rates, use of steroids, and endos-
copies in the year after their introduction. These results suggest the need for a prospective controlled trial to evaluate their effects on disease
course in patients with IBD.
(Inflamm Bowel Dis 2011;000:000–000)
Key Words: antidepressants, depression, ulcerative colitis, Crohn’s disease

ost studies, but not all,1–3 report that anxiety and

M depression are more prevalent in inflammatory bowel
disease (IBD) than in healthy4–8 or disease controls,9–11
used to treat concurrent mood disorders in IBD would also
improve disease course.

and that depression,12–15 like psychological stress16–18 and
adverse life events,19,20 can trigger relapse. If anxiety and
depression do have a significant impact on disease activity,
then established psychiatric treatments for depression might
be a useful addition to the IBD therapeutic armamentarium.
In this context, cognitive behavioral therapy (CBT)
improves mood and quality of life (QOL) scores,21 and in
some studies,22–24 including our own,25 may improve the
course of IBD itself. However, the effects of psychoactive
drugs on disease activity in IBD have not yet been properly
evaluated.26 We hypothesized here that antidepressants
Received for publication June 20, 2011; Accepted July 7, 2011.
From the Centre for Digestive Diseases, Blizard Institute of Cell and Molecular
Science, Barts and the London School of Medicine and Dentistry, London, UK.
Reprints: Professor David Rampton, FRCP, DPhil, Endoscopy Unit, Royal
London Hospital, London E1 1BB, UK (e-mail: d.rampton@qmul.ac.uk).
Copyright VC 2011 Crohn’s & Colitis Foundation of America, Inc.
DOI 10.1002/ibd.21846
Published online in Wiley Online Library (wileyonlinelibrary.com).
MATERIALS AND METHODS
Study Design and Clinical Setting
Using previous methodology,25 we designed a retrospec-
tive case-matched evaluation of the effect of antidepressants
used to treat concomitant mood disorders in patients with IBD
at our hospital. Barts and the London NHS Trust is a tertiary
adult and pediatric IBD center located in East London, UK.
Index Patients
Patients with IBD diagnosed by conventional endo-
scopic, radiological, and histological criteria attending transi-
tion and adult outpatient clinics and treated with antidepres-
sants were identified using the electronic patient record. The
course of IBD was assessed during the year before (year 1)
and the year after (year 2) the initiation of any antidepressant
used to treat a concomitant mood disorder. Patients in whom a
date of commencement of the antidepressant was unknown, or
where the use of the antidepressant predated the diagnosis of

Inflamm Bowel Dis 1

Goodhand et al Inflamm Bowel Dis

FIGURE 1. STROBE27 diagram outlining identification, screening, and exclusion criteria of antidepressant patients and their controls.

IBD, or where subsequent follow-up was for less than a year, years, and disease duration 63 years were sought and then
were excluded (Fig. 1).27 Antidepressant class, type, pre- screened in detail to match for disease phenotype, baseline
scriber, and dose were recorded (Table 1). medications, surgeries, and relapse rate in year 1. Wherever
possible we sampled data on disease course in the years 1 and
2 matched to the equivalent time frames for duration of anti-
Control Patients depressant therapy in the index case.
Consecutive attendees to our specialist IBD outpatient
clinics between March and August 2010 were screened for
inclusion as controls (Fig. 1). Data were number-coded to
blind investigators identifying potential matches and demo-
graphic data were then recorded. Potential matches for each Variables
index patient, on the grounds of gender, age at diagnosis 65
Demographic data, disease phenotype according to the
Montreal Classification,29 baseline (i.e., at the start of year 1)
TABLE 1. Antidepressant Class, Type, and Doses disease activity, C-reactive protein (CRP), hemoglobin, and
Prescribed platelet count as well as medications and previous surgery
were recorded from the electronic patient record (Table 2).
Median The outcome measures assessed in years 1 and 2 were: the
Antidepressant [Range] number of relapses, number of endoscopic procedures (exclud-
Class Antidepressant N (%) Dose (mg)
ing those done for routine cancer surveillance), number of
SSRI Citalopram 10 (29%) 20 [20–60] hospital admissions and outpatient attendances, numbers of
courses of steroids and relapse-related use of other IBD medi-
Fluoxetine 7 (21%) 20 [20–60]
cations, e.g., an increase in 5-aminosalicylate (5-ASA) dosage
Sertraline 3 (9%) 50 [50–100]
or introduction of antibiotics, immunosuppressants (thiopurine
Paroxetine 1 (3%) 20
or methotrexate), or anti-tumor necrosis factor (anti-TNF)
TCA Amitriptyline 5 (12%) 22.5 [10–25]
therapy. Disease activity was defined for ulcerative colitis
Lofepramine 1 (3%) 70
(UC) as the presence of diarrhea and rectal bleeding, and a
NaSSa Mirtazepine 5 (12%) 30 [15–45] relapse as the presence of these symptoms with a step-up in
SNRI Venlafaxine 2 (3%) 150 mg IBD medication. Disease activity in Crohn’s disease (CD) was
SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; defined as the presence of abdominal pain and/or diarrhea
NaSSa, noradrenergic and specific serotonergic antidepressant; SNRI, a and/or a CRP >10 mg/L, and a relapse as the presence of
serotonin-noradrenaline reuptake inhibitor.
these features with a step-up in IBD medication.

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Inflamm Bowel Dis Effect of Antidepressants in IBD

TABLE 2. Baseline Characteristics of the Antidepressant Group and Their Controls

Characteristic Antidepressants [29] Controls [29] P-value

Sex Male 12 [41%] 12 [41%] 1

Ethnicity White Caucasian 27 [85%] 22 [76%] 0.12
South Asian 2 [12%] 4 [14%]
Afro-Caribbean — 3 [10%]
Disease duration Median age at diagnosis (yrs) [range] 26 [13–72] 29 [12-62] 0.43
Median disease duration (yrs) [range] 5.2 [1–40] 4.2 [1-31] 0.19
Disease type Crohn’s disease 15 [52%] 15[52%] 1
Ulcerative colitis 14 [48%] 14 [48%]
Crohn’s disease A1: Age
16 4 [26%] 3 [20%] 0.91
(Montreal Classification) A2: 17-40 10 [67%] 11 [73%]
A3: >40 1 [7%] 1 [7%]
L1: Ileal 5 [33%] 5 [33%] 1
L2: Colonic 1 [7%] 1 [7%]
L3: Ileocolonic 9 [60%] 9 [60%]
þ L4: Upper GI 3 [20%] 1 [7%] 0.60
B1: Inflammatory 9 [60%] 9 [60%] 0.14
B2: Stricturing 3 [20%] 6 [40%]
B3: Penetrating 3 [20%] —
þ p: Perianal 3 [20%] 3 [20%] 1
Medication Corticosteroids 4 [27%] 4 [27%] 1
5-ASA 7 [47%] 10 [66%] 0.46
Immunosuppressiona 8 [53%] 8 [53%] 1
Anti-TNF 1 [6%] 1 [6%] 1
Surgery Previous laparotomy 5 [39%] 7 [44%] 0.71
UC (Montreal Classification) E1: Proctitis 2 [14%] 1 [7%] 0.67
E2: Left 8 [57%] 7 [50%]
E3: Total 4 [29%] 6 [43%]
Medication 5-ASA 13 [93%] 14 [100%] 1
Prednisolone 4 [29%] 4 [29%] 1
Immunosuppressiona 6 [43%] 6 [43%] 1
Anti-TNF — — —
Surgery Colectomyb 1 [6%] 1 [6%]
Activity Active IBD 12 [41%] 12 [41%] 1
Number of relapses (year1) 1 [0-4] 1 [0-4] 1
Mean [SEM] C-reactive protein [mg/l] 3.8 [0.94] 12 [7.85] 0.33
Mean [SEM] hemoglobin [g/dl] 13.4 [0.32] 13.1 [0.7] 0.74
Mean [SEM] platelet count [x109] 259 [21.4] 349 [38.4] 0.07
a
Either a thiopurine or methotrexate.
b
The patient on an antidepressant had had a left hemicolectomy for a benign hamartoma, his control had undergone a right hemicolectomy for an appendi-
ceal mucocele. P-values were determined using Wilcoxon’s signed rank test, chi-squared analysis, and paired t-tests.Continuous data are reported as me-
dian [ranges] unless otherwise stated. Discrete data are expressed as n [%].

Statistical Methods
Statistical analyses were undertaken using SPSS (v. 16
Chicago, IL) and Prism (v. 4, San Diego, CA) software. All
analyses were two-tailed and P-values were considered signifi-
cant if less than 0.05. Differences between the patients treated
with antidepressants and their controls at baseline were sought
using Wilcoxon’s signed ranks test and chi-squared analysis for
continuous and discrete variables, respectively. Paired t-tests
were used to compare baseline hematological variables. Out-
come measures are reported as medians (ranges), and compari-
sons between year 1 and year 2 within and between the case-
matched groups were made using Wilcoxon’s signed ranks test.

3
Goodhand et al Inflamm Bowel Dis

FIGURE 2. Relapse rates (A) and courses of steroids (B) in years 1 and 2 in the antidepressant group (n ¼ 29) and their matched controls
(n ¼ 29). Absolute values have been adjusted in order to demonstrate changes in individual data points; the solid bars indicate median
values, P-values were determined using Wilcoxon’s signed rank test.

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Inflamm Bowel Dis Effect of Antidepressants in IBD

TABLE 3. Effects of Antidepressant Treatment on IBD Activity Compared with That of Matched Controls
Antidepressant Controls
Changes in Antidepressant
Group (n¼29) (n¼29)
Group Versus Controls
Variable Median (Range) Year 1 Year 2 P-value Year 1 Year 2 P-value (P-value)

No. of relapses 1 [0–4] 0 [0–4] 0.002 1 [0–4] 1 [0–3] 0.21 0.03

Courses of steroids 1 [0–3] 0 [0–4] <0.001 1 [0–2] 1 [0–3] 0.33 0.07
Changes in 5-ASA/antibiotics 0 [0–6] 0 [0–1] 0.06 0 [0–3] 0 [0–2] 0.09 0.54
Changes in immunosuppression 0 [0–4] 0 [0–2] 0.28 0 [0–2] 0 [0–4] 0.81 0.42
New anti-TNF 0 [0–1] 0 [0–0] — 0 [0–1] 0 [0–1] 1 0.50
No. of outpatient attendances 4 [1–13] 4 [0–11] 0.33 6 [1–12] 4 [0–14] 0.22 0.73
No. of endoscopies 0 [0–2] 0 [0–1] 0.02 0 [0–1] 0 [0–3] 0.25 0.01
No. of hospital admissions 0 [0–2] 0 [0–3] 0.84 0 [0–2] 0 [0–2] 0.84 0.70
Median values (ranges) are shown in the year before (year 1) and after (year 2) commencing an antidepressant. P-values were determined using
Wilcoxon’s signed rank test.

Ethical Considerations Baseline Demographics

This study was designed to evaluate a clinical service
and did not require formal ethical approval, according to UK
National Research Ethics Service (NRES) guidelines.29
RESULTS
Antidepressant-treated Patients
A total of 34 IBD patients treated with an antidepres-
sant who had a complete dataset for years 1 and 2 were
identified (Table 1). The antidepressants were initiated by
the patient’s general practitioner in 68% (23/34), by a gas-
troenterologist in 21% (7/34), and by a psychiatrist in 12%
(4/34) cases. The five patients taking amitriptyline were
prescribed low doses, all less than 25 mg per day (Table
1), in the range frequently used for chronic pain and irrita-
ble bowel syndrome,30,31 and subtherapeutic for the man-
agement of depression. They were therefore secondarily
excluded (Fig. 1), leaving 29 patients.
Control Patients
In all, 2449 consecutive scheduled appointments in
1056 IBD patients attending our specialist IBD outpatient
clinics between March and August 2010 were screened for
inclusion (Fig. 1). There were 303 potential matches for
the 34 antidepressant patients on the grounds of gender,
age at diagnosis, and disease duration identified: the num-
ber of potential matches per patient was 8 (3–44) (median
[range]). We were able to sample data on disease course
matched to the equivalent time frames for duration of anti-
depressant therapy in the index case in 74% (25/34)
patients; in the remainder, sampling time frames were
adjusted to match for the number of relapses in year 1.
As a consequence of our matching there were no
significant differences in the age at diagnosis, disease dura-
tion, disease phenotype, baseline medications, prior sur-
gery, or in baseline disease activity or relapse rate in year
1. Although not matched for directly, no significant differ-
ences were seen at baseline according to ethnicity, nor
were there differences in objective markers of inflammation
including hemoglobin, platelet count, or CRP (Table 2).
Disease Course
As shown in Figure 2 and Table 3, in the year after
starting (year 2), patients treated with an antidepressant had
fewer relapses (0 [0–4) and associated courses of steroids
(0 [0–4]) than in the year before starting the antidepressant
(year 1) (1 [0–4] P ¼ 0.002; 1 [0–3] P < 0.001, respec-
tively). There were no significant differences in these varia-
bles between years 1 and 2 in the control group, and there
was at least a trend to a statistically significant difference
between the changes seen in each of these two variables in
the two groups (Table 3, Fig. 2). Corticosteroids were used
for treatment of 39%–42% of relapses occurring in either
year 1 or 2 in both the antidepressant and control groups.
There was a trend toward, but not a statistically sig-
nificant fall in the use of 5-ASA/antibiotics in both groups
in year 2 compared with the first year. No differences were
seen in relapse-related use of other medications (immuno-
suppression or anti-TNF) between years in either group.
Subanalysis by disease type showed that in both UC and
CD there was at least a trend toward a reduction in relapse
rates (UC year 1: 1 [0–4] vs. year 2: 0 [0–2] (P < 0.01);
and CD year 1: 1 [0–2] vs. year 2: 0 [0–1] (P ¼ 0.09) and
associated use of steroids (UC year 1: 1 [0–3] vs. year 2: 0
[0–4] (P < 0.05); and CD year 1: 0.5 [0–2] vs. year 2: 0

5
Goodhand et al
[0–1] (P < 0.05)); these changes were not seen in the dis-
ease-matched controls.
The numbers of hospital admissions and outpatient
appointments did not change significantly between years 1
and 2 in either group (Table 3, Fig. 2). However, the num-
ber of endoscopies undertaken in year 2 was significantly
less than in year 1 in those patients taking antidepressants,
a difference not seen in the control group.
The small numbers of patients taking antidepressants
other than a selective serotonin reuptake inhibitor (SSRI)
meant that subanalysis by class of antidepressant was
futile.
DISCUSSION
In recent years there has been increasing recognition
by doctors as well as patients that depression can worsen
the course of IBD.12–15 Studies in rodents32 and transla-
tional work33,34 in man have made apparent some of the
humoral and neuronal routes by which mood, acting
through the hypothalamo–pituitary–adrenal axis and the au-
tonomic nervous system, may influence inflammatory and
immune function in the gut. Whatever the mechanisms
involved prove to be, treatments that alleviate stress and
improve mood could help symptoms and disease activity in
IBD. Antidepressants are generally well tolerated and are
successful in relieving psychological symptoms in about
30% of patients.35,36 Moreover, they are commonly used
by gastroenterologists to treat psychological distress associ-
ated with irritable bowel syndrome and are not perceived
to be harmful in IBD.37 The effects of psychoactive drugs
on disease activity or mood in IBD have not yet been prop-
erly evaluated.
Antidepressants in IBD
Uncontrolled case reports of the use of bupro-
pion,38,39 paroxetine,26 and phenelzine40 in patients with
IBD have reported improvements not only in depression
and social disability scores but also in IBD symptom
scores. In contrast, data from a single open-label study of
paroxetine (20–40 mg) in eight IBD patients with major
depression treated for 8 weeks reported improvements in
depression and social disability scores but not in IBD activ-
ity.41 More recently, a randomized placebo-controlled dou-
ble-blind trial of imipramine for 8 weeks in 50 patients
with mild to moderately active UC claimed to show that
the antidepressant improved both disease activity, measured
using the Powell-Tuck score and mood.42 However, the
study was compromised by several aspects of trial design.
First, patients were randomized regardless of their mood
status; at baseline the treated patients were more depressed
than the controls. Second, the tricyclic antidepressant used
may have improved symptoms through a direct anticholi-
nergic constipating effect and no objective markers of
6
Inflamm Bowel Dis
inflammation were included in the analysis to confirm the
significance of the improvement in symptom scores. Lastly,
the dose of imipramine used was low (10–50 mg/day), in
the range used for chronic pain and irritable bowel
syndrome.30,31
Key Results and Interpretation of the Study
The results of our exploratory study suggest that anti-
depressants used to treat concomitant mood disorders in
patients with IBD improve relapse rates and the associated
use of corticosteroids compared with matched controls,
suggesting that antidepressants may improve disease course
in IBD. Conversely, our results give no signals to suggest
that antidepressants might have any adverse effect on the
symptoms or activity of IBD.
Limitations
Because of our retrospective data collection, in par-
ticular for the Montreal Classification, our results are
potentially subject to interpretation bias and bias because
of missing data. Furthermore, because this is a study of the
effects of antidepressants on disease course, we have no
data pertaining to the efficacy of the antidepressant in treat-
ing the mood disorder itself or whether improvements in
mood predict improvements in disease course. It is also
possible that because we did not routinely enquire about
mood in all our IBD outpatients, a proportion of the con-
trols may have had an unrecorded mood disturbance. Our
sample size is small. Indeed, it is remarkable that so few
of our IBD patients were treated with antidepressants given
the increased prevalence of mood disorders in IBD patients
compared with the general population.21 Suboptimal cap-
ture of all of our patients who were taking antidepressants
could have contributed to this: some may have withheld
this drug history, perceiving during follow-up consultation
that it is not related to their IBD. It is notable too, given
the reported association of mood disorders with active dis-
ease,21 that most patients were started on antidepressants
when their disease was quiescent. Despite our careful
matching, there was a non-significant trend to a higher
CRP and platelet count at the start of year 1 in the control
group; it is conceivable that these patients were more pre-
disposed to relapse than the antidepressant group. Lastly,
because the majority of patients were taking an SSRI we
were unable to stratify the response according to antide-
pressant type. The small sample size also limits the degree
to which conclusions about responses according to disease
type can be made, although our subanalysis suggests
that antidepressants may be useful adjuncts in both UC
and CD.
Inflamm Bowel Dis
External Validity
Allowing for the limitations above, our findings are
consistent with the, albeit limited, data from previous stud-
ies of antidepressants in IBD.26,38–42 However, because this
is a single-center cohort study and our unit is a tertiary
referral center for IBD care, it is possible that we included
patients with more severe disease than those seen routinely
in other healthcare settings. It is unknown to what extent
our findings are applicable to less severe, for example pop-
ulation- or community-based cohorts or to nondepressed
patients. In the latter context, it is conceivable that the anti-
depressants studied here, in the main SSRIs, were having a
direct effect on serotonin and noradrenaline receptors in
the gut rather than only in the brain and on mood directly.
Data on the efficacy of the antidepressant on psychological
outcomes, as well as on the efficacy of antidepressants in
nondepressed individuals, would help conclusions to be
drawn as to whether improvements in disease course were
due to improvements in mood or symptom perception, or
through a direct effect on colonic motility and/or pain
thresholds.
CONCLUSION
Antidepressants, when used to treat concomitant
mood disorders in IBD, seem to reduce relapse rates and
the need for steroids, as well as use of endoscopy, in the
year after their introduction. Appropriately designed
randomized controlled trials are required to confirm
whether or not psychoactive medications improve the
course of IBD, either when given alone or as an adjunct to
conventional anti-inflammatory therapy: such studies
should also compare the safety and tolerance of antidepres-
sant therapy with those of steroids, immunosuppressants,
and/or biologics. In the meantime, IBD patients should be
screened for associated mood disorders and be offered
treatment, at the very least to improve their mood, in the
form of graded exercise, counseling/CBT, and/or an antide-
pressant, as recommended by the UK National Institute of
Clinical Excellence (NICE) guidelines for management of
depression.43
ACKNOWLEDGMENTS
J.R.G. participated in study design, collected and ana-
lyzed the datasets, and prepared the article. F.G. and A.M.
collected the antidepressant dataset. Y.K. identified the
controls. M.W. and L.L. participated in data interpretation
and preparation of the article. D.S.R. conceived the study
and participated in study design, interpretation of its
results, and preparation of the article. We thank Dr. James
Lindsay and Dr. Nick Croft for allowing us to include their
patients. All authors approved the final article. We also
thank Crohn’s and Colitis UK and CORE/British Society
Effect of Antidepressants in IBD
of Paediatric Gastroenterology Hepatology and Nutrition
(BSPGHAN) for funding J.R.G.’s research. We have no
financial conflicts of interest to disclose.
REFERENCES
1. Helzer JE, Stillings WA, Chammas S, et al. A controlled study of the
association between ulcerative colitis and psychiatric diagnoses. Dig
Dis Sci. 1982;27:513–518.
2. Robertson DA, Ray J, Diamond I, et al. Personality profile and affec-
tive state of patients with inflammatory bowel disease. Gut. 1989;30:
623–626.
3. Mikocka-Walus AA, Turnbull DA, Moulding NT, et al. Does psycho-
logical status influence clinical outcomes in patients with inflamma-
tory bowel disease (IBD) and other chronic gastroenterological
diseases: an observational cohort prospective study. Biopsychosoc
Med. 2008;2:11.
4. Addolorato G, Capristo E, Stefanini GF, et al. Inflammatory bowel
disease: a study of the association between anxiety and depression,
physical morbidity, and nutritional status. Scand J Gastroenterol.
1997;32:1013–1021.
5. Kovacs Z, Kovacs F. Depressive and anxiety symptoms, dysfunctional
attitudes and social aspects in irritable bowel syndrome and inflamma-
tory bowel disease. Int J Psychiatry Med. 2007;37:245–255.
6. Kurina LM, Goldacre MJ, Yeates D, et al. Depression and anxiety in
people with inflammatory bowel disease. J Epidemiol Commun
Health. 2001;55:716–720.
7. Tarter RE, Switala J, Carra J, et al. Inflammatory bowel disease: psy-
chiatric status of patients before and after disease onset. Int J Psychia-
try Med. 1987;17:173–181.
8. Walker JR, Ediger JP, Graff LA, et al. The Manitoba IBD cohort
study: a population-based study of the prevalence of lifetime and 12-
month anxiety and mood disorders. Am J Gastroenterol. 2008;103:
1989–1997.
9. Filipovic BR, Filipovic BF, Kerkez M, et al. Depression and anxiety
levels in therapy-naive patients with inflammatory bowel disease and
cancer of the colon. World J Gastroenterol. 2007;13:438–443.
10. Magni G, Bernasconi G, Mauro P, et al. Psychiatric diagnoses in ul-
cerative colitis. A controlled study. Br J Psychiatry. 1991;158:
413–415.
11. Helzer JE, Chammas S, Norland CC, et al. A study of the association
between Crohn’s disease and psychiatric illness. Gastroenterology.
1984;86:324–330.
12. Mardini HE, Kip KE, Wilson JW. Crohn’s disease: a two-year pro-
spective study of the association between psychological distress and
disease activity. Dig Dis Sci. 2004;49:492–497.
13. Mittermaier C, Dejaco C, Waldhoer T, et al. Impact of depressive
mood on relapse in patients with inflammatory bowel disease: a pro-
spective 18-month follow-up study. Psychosom Med. 2004;66:79–84.
14. Persoons P, Vermeire S, Demyttenaere K, et al. The impact of major
depressive disorder on the short- and long-term outcome of Crohn’s
disease treatment with infliximab. Aliment Pharmacol Ther. 2005;22:
101–110.
15. Deter HC, Scheidt CE. [Attachment and development within
psychosomatic medicine.] Psychother Psychosom Med Psychol. 2008;
58:303.
16. Levenstein S, Prantera C, Varvo V, et al. Stress and exacerbation in
ulcerative colitis: a prospective study of patients enrolled in remission.
Am J Gastroenterol. 2000;95:1213–1220.
17. Bitton A, Dobkin PL, Edwardes MD, et al. Predicting relapse in
Crohn’s disease: a biopsychosocial model. Gut. 2008;57:1386–1392.
18. Bernstein C, Singh S, Graff L, et al. A prospective population based
study of triggers of flare of IBD. DDW. Chicago; 2009.
19. Duffy LC, Zielezny MA, Marshall JR, et al. Relevance of major stress
events as an indicator of disease activity prevalence in inflammatory
bowel disease. Behav Med. 1991;17:101–110.
20. Bitton A, Sewitch MJ, Peppercorn MA, et al. Psychosocial determi-
nants of relapse in ulcerative colitis: a longitudinal study. Am J
Gastroenterol. 2003;98:2203–2208.
7
Goodhand et al
21. Goodhand JR, Wahed M, Rampton DS. Management of stress in
inflammatory bowel disease: a therapeutic option? Expert Rev Gastro-
enterol Hepatol. 2009;3:661–679.
22. Milne B, Joachim G, Niedhardt J. A stress management programme
for inflammatory bowel disease patients. J Adv Nurs. 1986;11:
561–567.
23. Elsenbruch S, Langhorst J, Popkirowa K, et al. Effects of mind-body
therapy on quality of life and neuroendocrine and cellular immune
functions in patients with ulcerative colitis. Psychother Psychosom.
2005;74:277–287.
24. Langhorst J, Mueller T, Luedtke R, et al. Effects of a comprehensive
lifestyle modification program on quality-of-life in patients with ulcer-
ative colitis: a twelve-month follow-up. Scand J Gastroenterol. 2007;
42:734–745.
25. Wahed M, Corser M, Goodhand JR, et al. Does psychological coun-
seling alter the natural history of inflammatory bowel disease?
Inflamm Bowel Dis. 2010;16:664–669.
26. Mikocka-Walus AA, Turnbull DA, Moulding NT, et al. Antidepres-
sants and inflammatory bowel disease: a systematic review. Clin Pract
Epidemol Ment Health. 2006;2:24.
27. Vandenbroucke JP, von Elm E, Altman DG, et al. Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE):
explanation and elaboration. PLoS Med. 2007;4:e297.
28. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated
clinical, molecular and serological classification of inflammatory bowel
disease: report of a Working Party of the 2005 Montreal World Con-
gress of Gastroenterology. Can J Gastroenterol. 2005;19(Suppl A):5–36.
29. NRES. Differentiating audit, service evaluation and research.
Available at: http://wwwnresnpsanhsuk/applications/guidance/
research-guidance/?entryid62 ¼ 66988. 2007.
30. Ford AC, Marwaha A, Lim A, et al. Efficacy of antidepressants and
psychological therapies in irritable bowel syndrome: systematic review
and meta-analysis. Gut. 2009;58:367–378.
31. Verdu B, Decosterd I, Buclin T, et al. Antidepressants for the treat-
ment of chronic pain. Drugs. 2008;68:2611–2632.
Inflamm Bowel Dis
32. Maunder RG, Levenstein S. The role of stress in the development and
clinical course of inflammatory bowel disease: epidemiological evi-
dence. Curr Mol Med. 2008;8:247–252.
33. Mawdsley JE, Jenkins DG, Macey MG, et al. The effect of hypnosis
on systemic and rectal mucosal measures of inflammation in ulcerative
colitis. Am J Gastroenterol. 2008;103:1460–1469.
34. Mawdsley JE, Macey MG, Feakins RM, et al. The effect of acute psy-
chologic stress on systemic and rectal mucosal measures of inflamma-
tion in ulcerative colitis. Gastroenterology. 2006;131:410–419.
35. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes
with citalopram for depression using measurement-based care in
STAR*D: implications for clinical practice. Am J Psychiatry. 2006;
163:28–40.
36. Krishnan V, Nestler EJ. The molecular neurobiology of depression.
Nature. 2008;455:894–902.
37. Mikocka-Walus AA, Turnbull DA, Moulding NT, et al. ‘‘It doesn’t do
any harm, but patients feel better’’: a qualitative exploratory study on
gastroenterologists’ perspectives on the role of antidepressants in
inflammatory bowel disease. BMC Gastroenterol. 2007;7:38.
38. Kane S, Altschuler EL, Kast RE. Crohn’s disease remission on bupro-
pion. Gastroenterology. 2003;125:1290.
39. Kast RE, Altschuler EL. Remission of Crohn’s disease on bupropion.
Gastroenterology. 2001;121:1260–1261.
40. Kast RE. Crohn’s disease remission with phenelzine treatment. Gastro-
enterology. 1998;115:1034–1035.
41. Walker EA, Gelfand MD, Gelfand AN, et al. The relationship of cur-
rent psychiatric disorder to functional disability and distress in patients
with inflammatory bowel disease. Gen Hosp Psychiatry. 1996;18:
220–229.
42. Esmaeili A, Masjedi M, Ani A, et al. New insights of anti-depressant
therapy in the management of ulcerative colitis. Gastroenterology.
2008;134:A-100.
43. NICE. Depression: treatment and management of depression in adults
including adults with a chronic health problem. NICE. Available at:
http://www.nice.org.uk/nicemedia/live/12329/45890/45890.pdf 2009.