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.

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.

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 < .02). Likewise, the patients’ mean pain index score diminished, with desipramine being significantly superior to placebo (P < .025). Self-reported diarrhea decreased in patients in all 3 cohorts and significant reduction was noted in the desipramine group compared with the placebo group (P < .005).

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 < .02). Likewise, the patients’ mean pain index score diminished, with desipramine being significantly superior to placebo (P < .025). Self-reported diarrhea decreased in patients in all 3 cohorts and significant reduction was noted in the desipramine group compared with the placebo group (P < .005).

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 < .05). This would suggest quite definitively that the beneficial effect of desipramine was not related to its anticholinergic effect because desipramine was able to produce improvement where a potent GI motility–altering drug, atropine, had no significant effect.

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.