Mikocka_edit_Layout 1 05/10/2009 10:58 Page 52
Inflammatory Bowel Disease
Discussion mood and coping mechanisms. Evidence for the anti-inflammatory
The recently published data examined in the current study provide properties of antidepressants relies heavily on findings in animal
further support that antidepressants may reduce inflammatory models. A number of human studies have provided some insights
activity in IBD. The evidence originates from randomised controlled into the anti-inflammatory effects of antidepressants, but
trials in animal models of IBD where desipramine and fluoxetine methodological problems (such as sample size) and at times
conflicting results demand caution in their interpretation.
21,22
One of
the more consistent findings has been the effect of therapy with
antidepressants on circulating cytokine profiles. Pro-inflammatory
Recent studies in animal models
cytokines, interleukin-6 (IL-6) and interferon-γ (INF-γ) normalise with
of colitis have supported a positive
long-term therapy and anti-inflammatory cytokines such as IL-10
increase, with consequent suppression of the INF-γ/IL-10 ratio.
23–26
impact of antidepressants on
Furthermore, although the effects seem to occur with a spectrum of
intestinal inflammation.
antidepressants, there is some evidence that fluoxetine may be the
most potent in this effect in both human
23
and animal studies,
27,28
and
the effects may be more evident in low doses.
reduced the severity of intestinal inflammation. The studies varied The second putative mechanism of action of antidepressants is by
in quality; for example, sample sizes were small and study reducing susceptibility to stress. Indeed, in animal models,
procedures were incompletely described in some. However, the antidepressants alleviate the stress response
29,30
and reduce
positive effect was observed uniformly across different animal susceptibility to stress.
31
Thus, if stress contributes to exacerbation
models of colitis. While such observations increase confidence in of IBD,
1
reducing people’s susceptibility to stress should have a
extrapolating such effects to the human situation, the lack of well preventative effect. Therefore, even if antidepressants do not have
powered and designed randomised controlled trials in patients with anti-inflammatory properties, they could still be effective in
CD and/or UC hampers its application. preventing IBD relapses.
Other recent studies have addressed issues in the current use of The way antidepressants reduce the susceptibility to stress might also
and attitudes towards antidepressants in patients with IBD. Use involve inflammatory cytokines. Indeed, it has been suspected that
of antidepressants in such patients is clearly common, but the depression is an inflammatory or even psychoneuroimmunological
32
reasons for such use appear to be directed towards their positive condition that causes increasing production of pro-inflammatory
effect on overall health, which is likely to be visible on disease cytokines (IL-1, IL-6 and INF-γ).
33
A cause–effect relationship between
activity indices, rather than towards their anti-inflammatory cytokines and depression is perhaps best seen in cancer patients
properties specifically. For example, only two out of 14 undergoing cytokine therapy (ILs plus INF)
34
and by high rates of
gastroenterologists who had used antidepressants in patients with depression in patients with hepatitis C virus infection during
IBD had specifically noticed a positive influence of this treatment treatment with IFN-α.
35
Kulmatycki and Jamali
21
hypothesise that
on IBD activity. However, the methodologies used in this study cytokines induce depression and/or anxiety by affecting the
addressed general opinions and experience rather than examining hypothalamus–pituitary–adrenal (HPA) axis, which is a mechanism by
specific cases and their particular outcomes. Overall, the which the brain responds to stress. Other researchers have suggested
usefulness of antidepressants in IBD was supported, but it is that psychological stress by inducing inflammation influences onset
unclear whether antidepressants are mainly prescribed for and progression of depression.
36
Existing studies report associations
psychological or somatic problems. Evidence of the effect of this of depression with pro-inflammatory cytokines, but there is no
treatment is also by and large lacking as there are no studies evidence to indicate whether these cytokines cause depression or
comparing IBD patients taking and not taking antidepressants. Such just sustain it.
37
studies are needed and could be conducted retrospectively in
clinics that collect a comprehensive documentation of their
patients. The use of antidepressants could then be correlated with
Despite this gap in evidence,
number of relapses, disease activity and general wellbeing over
time if such data were available.
gastroenterologists use antidepressants
in a subset of such patients, most likely
The studies in general addressed positive aspects of antidepressant
medication. Adverse effects are well documented with these drugs.
for depressive manifestations rather than
However, one study
20
described an association between their use
for inflammation itself.
and the development of lymphocytic or collagenous colitis. A causal
relationship was not well established, but some antidepressants
may need to be added to a list of medications that may possibly The high prevalence of psychological problems in inflammatory
induce microscopic colitis. diseases supports the psychoneurological concept of depression.
38
Moreover, anti-TNF treatment, which potently reduces inflammatory
Mechanistically, antidepressants might have benefits in patients with activity in patients with IBD, improves quality of life and decreases
IBD via direct anti-inflammatory actions or reducing susceptibility, depression and fatigue.
39
Kubera et al.
23
pointed out that fluoxetine may
alone or in combination. Alternatively, they might improve quality of have higher therapeutic efficacy in cases of depression when
life without specific effects on disease activity via the elevation of inflammatory markers are particularly high and, thus, this could be
52 EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76