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Functional GI Disorders: A Psychiatric Perspective

Functional GI Disorders: A Psychiatric Perspective

At first glance, it would seem
peculiar to be discussing GI
disorders in a psychiatric publication.
However, functional GI disorders
(FGIDs) represent a unique subset
of GI disorders that have strong psychiatric
implications beyond mere psychiatric
comorbidity and/or psychosocial
distress, which are indeed frequent
concomitants of these disorders. There
is increasing evidence that psychopharmacologic
and psychotherapeutic
management of FGIDs are highly effective
and, in many instances, surpass the
efficacy of standard medical treatment.
This article reviews the diagnostic criteria
for FGIDs and briefly discusses their
presentation and medical evaluation.
The role of the psychiatrist in treating
patients with these disorders is
discussed in greater detail, with an
emphasis on psychopharmacologic
treatment. In addition, the emerging and
quite exciting literature supporting the
role of psychotherapy and other behavioral
interventions in managing these
complex disorders and their psychosocial
concomitants, including psychiatric
comorbidity, will be discussed.

Epidemiology and
diagnostic criteria

FGIDs consist of a wide spectrum of
syndromes, which cross over and, in
some cases, overlap various anatomic
areas of the luminal gut. Although irritable
bowel syndrome (IBS) has traditionally
been the most studied and
written about, FGIDs constitute a
number of unique disorders, including
functional esophageal disorders (noncardiac
chest pain, functional dysphagia,
and globus sensation); functional
dyspepsia (pain, discomfort, nausea,
and other symptoms above the navel
in persons who do not meet the diagnostic
criteria for IBS); functional
abdominal pain syndrome; functional
abdominal bloating; functional diarrhea;
functional disorders of the biliary
tract, including Oddi sphincter; functional
disorders of the anorectal area,
such as pelvic floor dyssynergia; and
proctalgia fugax. Functional disorders
are somewhat unique in gastroenterologic
practice because they are diagnosed
using symptom-based criteria.

Building on the DSM model, international
teams of physicians and other
scientists expert in the area of FCIDs
have been gathering since 1988 on a
regular basis in Rome to develop symptom-
based criteria for the various
FGIDs. Similar to the DSM, as diagnostic
criteria have been developed and
field-tested, the Rome criteria have
evolved over time (Table).

The Rome working teams go beyond
merely formulating diagnostic criteria;
they also address important clinical and
research issues. For instance, the Rome
book includes working-team reports on
pediatric FGIDs, design for treatment
trials for FGIDs, and discussions of the
psychosocial aspects of FGIDs.1 The fact
that the psychosocial aspects of FGIDs
receive significant recognition in the
Rome process speaks to the importance
of these factors in properly diagnosing
and treating FGIDs.

Psychopharmacologic treatment

The earliest reported use of antidepressants
for GI disease was the use of
tricyclic antidepressants for the treatment
of peptic ulcer disease.2 Tricyclics
have subsequently been replaced by
more effective therapy based on updated
knowledge of pathophysiology. The
effectiveness of tricyclic antidepressants
can be influenced by their specific
receptor activity. For instance, highly
antihistaminic drugs, such as doxepin
and imipramine, are helpful in promoting
sleep. This could also influence their
ability to produce analgesia. In the
1970s and 1980s the analgesic properties
of antidepressants were discovered.
Antidepressant agents have been
successfully used for the management
of a wide variety of neuropathic pain
syndromes such as diabetic peripheral
neuropathy, postherpetic neuralgia,
migraine headache, cancer-related
pain, and other painful conditions. A
number of meta-analyses have supported
the usefulness of antidepressants
in these settings.3,4

Egbunike and Chaffee3 reviewed the
literature on antidepressants and chronic
pain and described a number of interesting
findings. The first was that the
analgesic effect of the drugs tended to
be independent of their antidepressant
effect. Second, they found that the doses
of heterocyclic antidepressants used to
achieve adequate analgesia seemed to
be lower than those considered effective
for the treatment of patients with
mood disorders. Finally, they noticed
that the onset of analgesia for neuropathic
pain syndromes ranged from 1
day to 10 weeks, with unpredictable
response time. This is considerably
shorter than the time usually required
to effectively treat patients with mood
and anxiety disorders.

GI Disorders

The tricyclic antidepressants have
also been found to play a role in treating
the visceral pain associated with
FGIDs. In 1987 Greenbaum and
colleagues5 undertook a landmark study
looking at the efficacy and mechanism
of action of antidepressants in functional
bowel disorders. In this study, 28 patients
with IBS completed a double-blind
crossover study using desipramine
versus atropine versus placebo in
random sequence. Atropine was used
as an active because the 0.4-mg dose
was able to simulate the antimuscarinic
effect of desipramine. All patients
underwent rectosigmoid manometry.
In addition, all were administered the
Hamilton depression rating scale
(HAM-D) and the Brief Psychiatric
Rating Scale (BPRS) to assess their
psychiatric status both on entry and exit
from the study. GI symptoms were also
recorded.

Twenty-eight patients completed the
entire protocol. Nine patients treated
with desipramine complained of side
effects that included anxiety, tremor,
palpitations, sweating, xerostomia, and
constipation. During the atropine phase
of the protocol, 7 patients also had side
effects, the most common being xerostomia,
constipation, and palpitations.
When GI symptoms were measured,
there was a significant reduction in the
number of stools per week in the
desipramine group compared with the
placebo group (P P P

Twenty-eight patients completed the
entire protocol. Nine patients treated
with desipramine complained of side
effects that included anxiety, tremor,
palpitations, sweating, xerostomia, and
constipation. During the atropine phase
of the protocol, 7 patients also had side
effects, the most common being xerostomia,
constipation, and palpitations.
When GI symptoms were measured,
there was a significant reduction in the
number of stools per week in the
desipramine group compared with the
placebo group (P P P

Overall motility did not differ significantly
between the 3 arms of the study,
except in patients with diarrheapredominant
IBS. In these patients,
overall motility was decreased with
desipramine compared with atropine (P

The investigators concluded that the
positive effect of desipramine was independent
of its antimuscarinic effect and
because of the dosage used in this
study, the lack of correlation with blood
concentrations, and the short duration
of the trial, the antidepressant effect of
desipramine was not responsible for the
improvement seen in the patients.
Likewise, study data demonstrated a
lack of correlation between patient
improvement and any documentable
changes in GI motility.

This study was the first to empirically
designate the unique effect of
antidepressants on functional bowel
disorders independent of any depressant
and anticholinergic effects. The
lack of correlation between changes in
psychiatric status and changes in GI
motility also spoke to the unique property
of desipramine to improve global
well-being in patients with functional
bowel disorders.

The literature has continued to move
in a positive direction supporting the
initial findings of Greenbaum and associates.
5 Jackson and coauthors6 undertook
a meta-analysis of published
randomized controlled trials on the use
of antidepressants for FGIDs. With the
application of quality criteria, 11
randomized placebo-controlled trials
of antidepressant therapy for FGIDs
were identified in the literature. These
included trials of amitriptyline, desipramine,
doxepin, clomipramine, trimipramine,
and mianserin (a serotonin
reuptake blocker not available in the
United States).

The authors concluded that the odds
of improvement in patients who
received antidepressant therapy for
functional bowel disorders was 4 to 2.
They calculated that an average of 3.2
patients needed to be treated to improve
1 patient symptom. They concluded
that the use of tricyclic antidepressants
as functional antidepressants was effective.
However, based on the literature
reviewed, they could not conclude
whether the effect was independent of
the antidepressant effect of the drug.

In an attempt to further elucidate the
role of antidepressants in functional
bowel disorders, in 2002 Brandt and
coworkers7 undertook a systematic
review of all pharmacotherapy for IBS
using evidence-based methodology.
They concluded that tricyclic antidepressants
are not more effective than
placebo in relieving global IBS symptoms.
The investigators used a subject
global assessment as the methodologic
gold standard to gauge effectiveness.
The methodology was based on recommendations
from the Rome working
teams on FGIDs; however, most of the
studies reviewed by Brandt and associates
were performed before these
recommendations existed, so the resulting
negative view of tricyclic antidepressants
may be unduly harsh.

Table
Comparison of the diagnostic criteria
for irritable bowel syndrome
  Manning Criteria
Abdominal pain that is relieved with a
bowel movement

Pain associated with more frequent
stools

Sensation of incomplete evacuation

Passage of mucus

Abdominal distention
  Rome Criteria
Continuous or recurrent symptoms of:

Abdominal pain, relieved with defecation
or associated with change in frequency
or consistency of stool;

and/or
Disturbed defecation (2 or more of):

Altered stool frequency

Altered stool form (hard or loose/watery)

Altered stool passage (straining or urgency, feeling of incomplete evacuation),
Passage of mucus

Usually with
Bloating or feeling of abdominal distention
  Revised Rome Criteria
At least 12 weeks or more, which need
not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has 2 out of 3 features:


Relieved with defecation;

and/or

Onset associated with a change in
frequency of stool;

and/or

Onset associated with a change in form (appearance) of stool.

Symptoms that cumulatively support the diagnosis of irritable bowel syndrome
  • Abnormal stool frequency (for research
    purposes "abnormal" may be defined as
    greater than 3 bowel movements per day
    and less than 3 bowel movements per
    week;
  • Abnormal stool form (lumpy/hard or
    loose/watery stool);
  • Abnormal stool passage (straining,
    urgency, or feeling of incomplete
    evacuation)

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