Functional GI Disorders and Psychiatry

Psychiatrists have traditionally not done well with patients who have functional somatic syndromes, most notably the common functional GI disorders (FGIDs; Table 1), such as irritable bowel syndrome (IBS; Table 2). Too often we hear gastroenterology colleagues giving feedback of unsatisfactory clinical outcomes following referrals to local psychiatric services. “They just don’t understand our patients. Why is that?” is their typical refrain.

This article provides background information on the FGIDs for psychiatrists and a review of recent research on the biopsychosocial mechanisms that contribute to the illness experience. Practical aspects of diagnosis of FGIDs and the rationale for treatment of patients with these disorders are discussed. Because most of the treatment options for these conditions involve the use of psychotropics and behavioral methods familiar to psychiatrists, there is considerable benefit in engaging more actively in the care of this often misunderstood and undertreated patient group.

Somatic presentations of depression in IBS

In patients with IBS, depression commonly presents with physical symptoms but no psychiatric symptoms. “Presentation bias” is often the cause of the subsequent failure to diagnose these psychiatric symptoms. However, with a consultation that is empathic, supportive, and well-timed, the information obtained can be considerable.

CASE VIGNETTE

A 35-year-old television producer presented with a 3-year history of increasing abdominal pain and distention. She described her pain as intermittent and cramping in nature. Pain intensity was 8 on a 10-point scale (10 being the worst pain possible), and it was hampering her ability to perform socially and at work. Her pain was temporarily relieved by defecation (predominantly diarrhea). She had no past psychiatric illness and denied any affective symptoms. She stressed that her only problem was her GI symptoms and her inability to effectively cope with them at work. She was anticipating benefit with the consultation liaison referral. She had already been referred to her local psychiatrist, which she described as “a waste of time” because of undue emphasis on areas of her life she believed were irrelevant to her symptoms.

After she was reassured that the consultation was primarily aimed at dealing with her gastric symptoms and her physical problems were sufficiently validated, she relaxed and the rapport improved. She then felt confident enough to volunteer more information about the degree to which her physical symptoms had been affecting her. She described her fatigue, anhedonia, sleep disturbance, weight loss, and low mood. She discussed marital and work stress “as a result of her physical problems” and her “perfectionism and self-criticism” that had always been a problem for her in similar situations.

Validation of physical symptoms, sufficient consultation time, and an awareness of not being blinded by presentation bias are of crucial importance in achieving mutually satisfactory outcomes for both patient and clinician. In an international study of 1146 patients with major depression, 69% reported only physical symptoms.¹ A similar study showed that in patients who presented with somatic complaints, 22% received a correct diagnosis of anxiety or depression. When patients presented with psychosocial problems, the diagnosis of a psychiatric problem was correct in 77%.²

What is already known about irritable bowel syndrome (IBS), bowel disorders, and the correlation with psychiatry?
? There is a very high incidence of psychiatric comorbidity in IBS. Study findings suggest that psychosocial factors play a key role in the etiology of IBS. Treatment with tricyclic antidepressants has established benefit.

What new information does this article provide?
? This article discusses practical aspects of diagnosis and the rationale for treatment. It also highlights the need to avoid missing a psychiatric diagnosis because of a “physical complaint only” presentation (ie, presentation bias). We review the use of psychopharmacology and the biosocial approach to address comorbid psychiatric complaints and to assist in the treatment of IBS directly through mechanisms that include neuroplasticity.

What are the implications for psychiatric practice?
? With greater understanding of new insights into the etiology of IBS, the psychiatrist will be called on to play a bigger role in treating patients with IBS and other related “functional” conditions. With a specialized knowledge and experience in the use of centrally acting psychopharmacological medications and concomitant psychotherapies, psychiatrists are an important part of the multidisciplinary team.

In patients who have physical complaints, the incidence of psychiatric comorbidity is higher. Kroenke and colleagues³ reported that with an increase in the number of physical symptoms, there is a dramatic increase in affective problems (Table 3), but these frequently go unnoticed and, therefore, untreated. A Department of Health campaign in England-“No health without mental health”-aims to address this imbalance.⁴

Because of a deeper and more integrative understanding of IBS and its pathophysiological determinants, there has been significant improvement in available treatment options. The earlier emphasis on abnormal motility did not fully explain the symptoms and pathogenesis of IBS and other FGIDs. It is now commonly accepted that visceral hypersensitivity (increased perception of peripheral sensation), intestinal per-meability, autonomic up-regulation, and psychosocial difficulties are instrumental in the dysregulation of the “brain-gut axis” (Figure 1).

Brain-gut axis dysregulation

Novel brain-gut neurotransmitter imaging and functional brain imaging show dysregulation of the brain-gut axis at the peripheral, spinal, and cerebral levels, all of which contribute toward the symptoms of IBS and other FGIDs.⁵ Neurotransmitters such as serotonin, norepinephrine, corticotropin-releasing factor, and opioids modify both motility and sensation in the gut. Therapies that target the CNS (psychotropic agents and behavioral treatments) are commonly used because of their effect on the serotonin and norepinephrine pathways, which cause direct modulation on all levels of the brain-gut axis. Serotonin and norepinephrine have been traditionally used to manage psychological and psychiatric disturbances that are commonly associated with GI disorders.⁶

Treatment of FGIDs with psychiatric agents has grown significantly in the past 2 decades. Close to 15% of patients with IBS are offered an antidepressant, and in many of these patients, a gastroenterologist initiates the treatment.⁷ Findings from a recent pharmacy database study in the United Kingdom indicate that patients for whom ongoing therapy for presumed IBS (antispasmodic medicines for a continuous 3-month period or more) is prescribed are 2 to 4 times more likely to be given CNS-acting drugs than controls (age- and sex-matched but with different chronic conditions).⁸ These include antidepressants (35.4%), anxiolytics (27.8%), antipsychotics (9.8%), and hypnosedatives (32.7%).

In a Swedish study, antidepressants were the second most commonly used drug category reported by IBS patients (antacids were first).⁹ In a recent survey of about 2000 patients with IBS, about 31% reported antidepressant use.¹⁰ However, the use of antidepressants as a treatment strategy for IBS remains questionable because of the complex nature of the disorder and lack of well-designed drug studies that would provide evidence of efficacy as well as variability among treatment end points.

Psychosocial factors and the biopsychosocial model in IBS

Since the days of Descartes, there has been a clear delineation in Western medicine between functional and organic conditions in the biomedical model of medicine. Using traditional diagnostic techniques, such as endoscopy and imaging, IBS was often considered at the functional end of the functional-organic spectrum. This would necessarily imply an absence of detectable structural abnormalities.

In the past 2 decades, there has been a great surge of research on motility, brain imaging, and neurotransmitters, which has given us the brain-gut axis-a working formulation now used ubiquitously by all international research groups. The pathophysiological understanding of the organic aspects of IBS has increased to such a degree that there is some debate whether we can still strictly call it a functional disorder.¹¹ The time of Descartes is being challenged, but unfortunately the negative stigma associated with functional conditions still lingers in the minds of many clinicians and patients.

One of the most clinically useful ways to conceptualize IBS is with the biopsychosocial model.¹¹ In this model, the influences of the CNS (at the spinal and cerebral levels), autonomic nervous system, and hypothalamic-pituitary-adrenal axis result in sensory and motor dysfunctions of the GI tract in a bidirectional way (Figure 1). The trigger can be peripheral (eg, GI infection, abdominal surgery) or central (eg, sexual abuse, personal losses, separation, deprivation). Psychosocial factors, such as alexithymia, catastrophization, ongoing work stress, and life events, often play an important role in the perpetuation and clinical manifestation of IBS through centrally mediated pathways.

There is proportionality between the importance of psychosocial factors and the severity of the functional disorder, to the degree that these factors are of major significance at the severe end of the functional spectrum. Persons with IBS commonly have a history of major stressful life events; those at the severe end of the spectrum may also perpetuate their symptoms by means of maladaptive illness behavior–like catastrophizing (Figure 2). The inability to incorporate and successfully deal with these psychosocial factors leads to more gastroenterology referrals and needless investigations at great cost, both financial and in quality of life.

Considering the natural history of IBS, psychosocial factors have been shown to significantly influence symptom generation and illness behavior during all stages of the illness: predisposing, precipitating, and perpetuating. As many as 75% of patients who presented at a tertiary referral center fulfilled the psychiatric diagnostic criteria for anxiety or depression.¹² This represents a marked increase in prevalence relative to patients seen in primary care or even in other general gastroenterology practices.

Independent of preexisting psychiatric diagnoses, upset feelings and distress as a result of chronic GI problems have negative effects on the patient’s mental health and physical state. In the biopsychosocial conceptual model, bidirectional influences constantly occur. For instance, psychiatric disorders and stress can enable IBS symptoms. Likewise, chronic IBS symptoms can lead to physiological effects. In addition, stress aggravates motility, lowers pain thresholds, and increases gut inflammation.

Gut distention in rats activates the locus ceruleus and leads to anxiety behavior; in humans, it can activate the anterior mid-cingulate and lower the affective pain threshold.¹³ Repeated physical examinations, poor patient understanding, and incomplete and often minimal or overly technical explanations from physicians add to a patient’s anxiety and fear, which perpetuates the severity of symptoms.¹⁴

It has been suggested that 15% to 45% of patients with IBS also fulfill the diagnostic criteria for somatization disorder.¹⁵ Patients with severe and refractory symptoms of IBS may have central dysregulation of their pain regulatory pathways (central sensitization).¹⁶ Because many of these pathways are activated by the same neurotransmitters as those for psychiatric conditions (eg, serotonin, norepinephrine, opiates), it may be prudent to use CNS monotherapy or a combination of pain medication and behavioral treatments (eg, cognitive-behavioral therapy, hypnotherapy). It is interesting to note that this could be effective even in the absence of psychiatric symptoms because the targets of treatment are the pathways rather than the psychiatric syndrome.

Psychotropics and psychotherapy

Treatment with antidepressants reduces pain and improves quality of life. It also has been associated with a significantly decreased relative risk of persistent IBS symptoms, with an estimated odds ratio of 2.6 to 4.2 for overall improvement.¹⁷ The number needed to treat for antidepressants is 3.2. For clinical practice, this means that for every 3 to 4 patients treated with antidepressant medication, a single patient will have significant improvement in symptoms. This rate compares favorably with GI medicines.¹⁷

Study results are mixed, and the therapeutic effect of antidepressants on visceral hypersensitivity is still unclear.¹⁸ The peripheral effects on the gut may be of secondary importance, however, because most of the patients who respond to antidepressants have not responded to conventional gut-acting medications. In an open-label physician-rated study, up to 80% of patients with IBS showed improvement while taking antidepressants, and adherence to treatment was higher than for any other treatments.⁷

SSRIs may improve global measures of well-being without having a direct correlation to pain ratings.¹⁹ Because morbidity associated with FGIDs is linked to the patient’s global distress, the use of SSRIs is good practice. Low-dose tricyclic antidepressants (TCAs) can also be effective in improving global measures of well-being.²⁰ TCAs are commonly used in IBS and other FGIDs because of their central and peripheral pain control effects.

The various classes of antidepressants have differential benefits in the treatment of FGIDs. Generally, the TCAs and the serotonin-norepinephrine reuptake inhibitors are used for pain regulation in patients with diarrhea-predominant IBS. The SSRIs are used for somatization associated with anxiety and phobias in patients with constipation-predominant IBS. Mirtazapine is used for nausea and low appetite.

Low doses of antipsychotics such as risperidone, olanzapine, and quetiapine have been found to be useful for visceral pain conditions associated with high arousal states with agitation (eg, globus hystericus, aerophagia, regurgitation, postprandial emesis).²¹ Mood stabilizers such as carbamazepine, sodium valproate, and pregabalin are helpful in chronic visceral pain disorders.²² The general approach is to first use monotherapy; if treatment response is poor, a combination of drugs in the same class or a different class can be used. Lower-dose combination therapy may have a better safety profile than high-dose monotherapy.

Neuroplasticity

Perhaps the most striking rationale for the use of centrally acting treatments in recent years is the concept of neuroplasticity. Antidepressants, and possibly psychotherapy, can promote neurogenesis (ie, the regrowth of neurons) following the loss of cortical neurons in psychiatric trauma. Functional MRI studies have shown reduced neuron density in cortical brain regions involved in emotional and pain regulation in patients with pain disorders and with IBS.²³ Pain and psychological trauma (and particularly the combination of both) can be neurodegenerative-much like Alzheimer disease and Parkinson disease are.

In these psychological and pain conditions, antidepressants and other CNS-targeted agents and methods might offer some remedy by stimulating an increase in the levels of brain-derived neurotrophic factor following treatment. Brain-derived neurotrophic factor is a precursor to neurogenesis, and with prolonged treatment, neural increases that correlate with the degree of recovery from depression are seen.

The duration of antidepressant treatment also correlates with decreased relapse frequencies and recurrence of depression. These findings provide insight into neuronal growth regulation in key areas of the central pain matrix and provide new and important opportunities for research and patient care using antidepressants for the treatment of IBS.²⁴

Summary

As our understanding of the pathophysiology and psychopathology of IBS grows, it is becoming evident that the use of centrally acting psychopharmacological medications and concomitant psychotherapy should play an ever-increasing role in its treatment. Psychosocial factors play a key role in the etiology of IBS, especially at the more severe end of the spectrum (Figure 2). Psychiatrists have an important role in understanding and treating patients with IBS and other FGIDs as part of the multidisciplinary team.

References:

References

1.

Simon GE, VonKorff M, Piccinelli M, et al. An international study of the relation between somatic symptoms and depression.

N Engl J Med

. 1999;341:1329-1335.

2.

Kirmayer LJ, Robbins JM, Dworkind M, Yaffe MJ. Somatization and the recognition of depression and anxiety in primary care.

Am J Psychiatry

. 1993;150:734-741.

3.

Kroenke K, Jackson JL, Chamberlin J. Depressive and anxiety disorders in patients presenting with physical complaints: clinical predictors and outcome.

Am J Med

. 1997;103:339-347.

4.

Department of Health. Public Health, Adult Social Care, and the NHS.

http://www.dh.gov.uk

. Accessed September 30, 2011.

5.

Mayer EA, Naliboff BD, Craig AD. Neuroimaging of the brain-gut axis: from basic understanding to treatment of functional GI disorders.

Gastroenterology

. 2006;131:1925-1942.

6.

Mayer EA, Tillisch K, Bradesi S. Modulation of the brain-gut axis as a therapeutic approach in gastrointestinal disease.

Aliment Pharmacol Ther

. 2006;24:919-933.

7.

Whitehead WE, Levy RL, von Korff M, et al. The usual medical care for irritable bowel syndrome.

Aliment Pharmacol Ther

. 2004;20:1305-1315.

8.

Canavan JB, Bennett K, Feely J, et al. Significant psychological morbidity occurs in irritable bowel syndrome: a case-control study using a pharmacy reimbursement database.

Aliment Pharmacol Ther

. 2009;29:440-449.

9.

Faresjo A, Grodzinsky E, Johansson S, et al. Self-reported use of pharmaceuticals among patients with irritable bowel syndrome in primary care.

J Manag Care Pharm

. 2008;14:870-877.

10.

Drossman DA, Morris CB, Schneck S, et al. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit.

J Clin Gastroenterol

. 2009;43:541-550.

11.

Drossman DA. Presidential address: gastrointestinal illness and the biopsychosocial model.

Psychosom Med

. 1998;60:258-267.

12.

Lydiard RB. Irritable bowel syndrome, anxiety, and depression: what are the links?

J Clin Psychiatry

. 2001;62(suppl 8):38-45.

13.

Drossman DA, Whitehead WE, Toner BB, et al. What determines severity among patients with painful functional bowel disorders?

Am J Gastroenterol

. 2000;95:974-980.

14.

Posserud I, Agerforz P, Ekman R, et al. Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress.

Gut

. 2004;53:1102-1108.

15.

North CS, Downs D, Clouse RE, et al. The presentation of irritable bowel syndrome in the context of somatization disorder.

Clin Gastroenterol Hepatol

. 2004;2:787-795.

16.

North CS, Hong BA, Alpers DH. Relationship of functional gastrointestinal disorders and psychiatric disorders: implications for treatment.

World J Gastroenterol

. 2007;13:2020-2027.

17.

Ford AC, Talley NJ, Schoenfeld PS, et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.

Gut

. 2009;58:367-378.

18.

Kuiken SD, Tytgat GN, Boeckxstaens GE. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.

Clin Gastroenterol Hepatol

. 2003;1:219-228.

19.

Creed F, Fernandes L, Guthrie E, et al; North of England IBS Research Group. The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome.

Gastroenterology

. 2003;124:303-317.

20.

Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders.

Gastroenterology

. 2003;125:19-31.

21.

Grover M, Dorn SD, Weinland SR, et al. Atypical antipsychotic quetiapine in the management of severe refractory functional gastrointestinal disorders.

Dig Dis Sci

. 2009;54:1284-1291.

22.

Houghton LA, Fell C, Whorwell PJ, et al. Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome.

Gut

. 2007;56:1218-1225.

23.

Valet M, Gündel H, Sprenger T, et al. Patients with pain disorder show gray-matter loss in pain-processing structures: a voxel-based morphometric study.

Psychosom Med

. 2009;71:49-56.

24.

Drossman DA. Beyond tricyclics: new ideas for treating patients with painful and refractory functional gastrointestinal symptoms.

Am J Gastroenterol

. 2009;104:2897-2902.

25.

Drossman DA. The functional gastrointestinal disorders and the Rome II process.

Gut.

1999;45(suppl 2):II1-II5.

26.

Drossman DA, Chang L, Bellamy N, et al. Severity in irritable bowel syndrome: a Rome Foundation Working Team Report.

Am J Gastroenterol

. 2011;106:1749-1759.