BRAIN-GUT ISSUES
| NEW APPROACHES TO IRRITABLE BOWEL SYNDROME —Richard A. Weisiger, MD, PhD, Professor of
Medicine, University of California, San Francisco, School of Medicine
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| General considerations: definition— group of functional bowel disorders in which abdominal discomfort or pain is
associated with defecation or change in bowel habit and with features of disordered defecation, ie, constipation
or diarrhea; prevalence—20% of people have some symptoms of irritable bowel syndrome (IBS) in year; female-to-male
ratio ≈2:1 (however, men less likely to admit symptoms); most people do not see doctor about
problem; accounts for 0.5% of all health care expenditures; clinical issues—patient’s expectations (wants doctor
to prescribe something that makes them feel better or to make treatable diagnosis) rarely met; most drugs commonly
used for IBS ineffective in controlled trials; no clinically useful laboratory tests for confirming IBS; looking
for diagnosis can lead to increasingly invasive testing, unnecessary surgery, and overuse of medication
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| Diagnosis: diagnosis of exclusion no longer encouraged; new approach to make positive diagnosis as soon as possible;
alarm signs warranting thorough work-up—weight loss, anemia, elevated white blood cell count or erythrocyte
sedimentation rate, bleeding, fever, frequent nocturnal symptoms, or onset of symptoms after 40 yr of age;
diagnosis can be made with typical signs and symptoms where strong history of stress present; functional disorders
associated with IBS—fibromyalgia, chronic fatigue syndrome, interstitial cystitis, frequent headaches, anxiety
and panic disorders, and depression
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| Differential diagnosis: carbohydrate malabsorption—from lactose, sorbitol, or fructose; patient may report bloating,
pain, and diarrhea; counsel patient to limit soft drinks to 1 or 2 daily or replace regular milk with lactose-free
milk; celiac sprue—diarrhea, bloating, crampy pain; weight loss not always symptom; patient with diarrhea-predominant
disease should undergo serologic testing for antitissue transglutaminase or antiendomysial antibody;
giardiasis—consider in patients with exposure risk, eg, child care facility, contaminated water; diagnosed with
test of stool sample for giardiasis antigen or small bowel biopsy; miscellaneous—thyroid dysfunction, inflammatory
bowel disease, and chronic pancreatitis
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| Management: careful sympathetic history-taking; full assessment of psychologic and social history; ask at least
one open-ended question, eg, “is there anything going on in your life right now?” even if certain patient has IBS,
perform thorough physical examination; respectful questioning can determine history of childhood or current
abuse; history of childhood abuse or neglect common in patients with severe IBS; diagnosis of IBS can be made
after appropriate work-up for alarm signs and risk factors; provide patient with explanation, reassurance, and
frank account of prognosis
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 | Nonpharmacologic treatment: stress reduction—exercise, meditation, acupuncture, and hypnosis; healthy diet—
avoidance of high-fat foods (fat slows intestinal transit and worsens symptoms); address symptom triggers, eg,
milk ingestion, swallowing air from chewing gum, or narcotic-induced constipation; counseling—cost-effective,
especially for patient with history of abuse
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| Pharmacologic treatment: symptomatic treatment of constipation or diarrhea—laxatives and antidiarrheals; fiber
supplements not recommended (most increase bloating); antispasmodics, eg, dicyclomine (Bentyl), hyoscyamine
(Levsin), effective in 50% of patients, but no more effective than placebo; sedatives—benzodiazepines and phenobarbital
not recommended because of addictive effects; antidepressants—citalopram (Celexa) probably least
likely to produce gastrointestinal (GI) side effects; tricyclic antidepressants (TCAs), eg, nortriptyline, amitriptyline,
of proven value whether or not patient clinically depressed; effective only for pain; can be used in combination
with selective serotonin reuptake inhibitors (SSRIs); meta-analysis showed strong statistical evidence
TCAs effective for pain associated with IBS; consider 10 mg of nortriptyline or amitriptyline hs for patient with
abdominal pain who has trouble sleeping and does not have severe constipation; minimal side effects with low
dosage; tegaserod (Zelnorm)—partial 5-HT4 agonist; approved for constipation-predominant IBS and chronic
idiopathic constipation; appears safe; side effects include diarrhea; alosetron (Lotronex)—indicated for women
with diarrhea-predominant IBS; contraindicated for patient with constipation; available for restricted use (reduced
action of serotonin in gut produces severe constipation requiring surgery)
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| Pathophysiology: syndrome; may have several causes; early proposed mechanisms include colonic motility (“spastic
colon”), colonic inflammation (“spastic colitis”), mucus secretion, and psychosomatic factors; central nervous
system (CNS)—persistent stress response with release of stress hormones leading to altered pain processing, ie, visceral
hypersensitivity; mucosal inflammation—release of inflammatory mediators; peripheral nervous system—
may be hypersensitive; excessive gas formation—may be caused by bacterial overgrowth; IBS mechanisms must
explain—higher incidence in patients with anxiety and depression; altered pain sensation, including increased
sensitivity to gas and bowel distention; correlation of symptoms with psychiatric disorders (≈40%-50% of people
presenting to specialty clinic have anxiety, depression, phobias, or panic disorders); correlation of symptoms
with recent life stress; relation to childhood abuse and neglect; triggering by episode of acute stress
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| Inflammation: postinfectious IBS—presents after enteric infection, often Campylobacter (commonly called traveler’s
diarrhea); accounts for ≈25% of cases; indistinguishable from other forms of IBS; mucosal inflammation
may cause visceral hyperalgesia— normal mucosa has physiologic cell infiltrate; cell counts greater in colonic
mucosa of patients with IBS; evidence that mast cells release compounds that may affect nerve function and increase
pain; stress can cause degranulation of mast cells and release of histamine
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| Stress: stress response triggered by danger, pain, inflammation, or other factors; response in humans mediated by stress
hormones, particularly corticotropin-releasing factor (CRF), which triggers release of adrenocorticotropic hormone
(ACTH) in pituitary; ACTH then stimulates production of cortisol; stress hormones bring about autonomic responses,
behavioral effects, and peripheral effects; IBS associated with increased basal and/or transient elevations in
stress hormones, particularly CRF; responses meant to help person survive; speaker speculates IBS not disease, but
inappropriate stress response; symptoms of IBS occur with pain, triggering repressed painful memories; animal
model for IBS—newborn rats separated from mother for 3 hr daily (simulating neglect) appear to have baseline visceral
hypersensitivity, increased anxiety, and increased output of fecal pellets with stress as adults; may be model for
role of childhood abuse and neglect in humans; drugs that reduce central stress pathways should be most effective
treatment for IBS; astressin, when given to humans in phase 1 trials, caused liver function test abnormalities; is IBS
normal response to stress?—stress responses present in humans and other animals to enhance survival in ancestral
environment; these responses may no longer be appropriate; young animals born into unusually dangerous environment
cannot rely on parents for needs and must make permanent psychologic and physiologic changes to enhance
survival; lifelong anxiety helps to detect danger, promoting survival; increased basal stress hormones keep animal
prepared to escape danger; decreased somatic sensitivity helps overcome injuries during escape
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| IDENTIFYING THE PATIENT WITH ANXIETY —Judith Gerber, PhD, Clinical Assistant Professor, Departments
of Obstetrics and Gynecology and Psychiatry, University of Vermont, College of Medicine, Burlington
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| Generalized anxiety disorder (GAD): often goes undiagnosed; chronic anxiety persisting for >6 mo; often diagnosed
in perimenopausal period unaccompanied by panic attacks, phobias, or obsessions; 2 worries (eg, financial,
health) at any given time; interferes with daily functioning; symptoms— restlessness, easy fatigability,
irritability, difficulty concentrating, muscle tension, and sleep disturbances; 3 symptoms needed for diagnosis;
heightened by stress; basic fears of broad nature, eg, fear of losing control, not being able to cope, fear of failure,
abandonment, death, or disease; what patient feels more important than facts; therapy focuses on helping patient
face facts, rather than what they feel; patient has external locus of control, rather than internal locus of control;
vulnerable life stages— period after college can be difficult time for young adult dealing with life decisions; if
unsuccessful in finding meaningful work or life partner, person can begin to feel isolated and become depressed
and anxious; anxiety can cause patient to fear changing job or fear going back to school, leading person to stagnate
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| Posttraumatic stress disorder (PTSD): disabling anxiety following traumatic event, eg, natural disaster, war, motor
vehicle accident, rape; symptoms must persist for >1 mo; symptoms—repetitive thoughts, nightmares, flashbacks,
night terrors, numbness, and detachment or estrangement
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| Causes of anxiety disorders: physiologic and psychologic; variety of causes operating on different levels simultaneously;
long-term predisposing causes—heredity and environment; childhood environment—overly cautious
parenting can lead to specific phobias; overly critical parents with excessively high standards can lead to obsessive-compulsive
disorder (OCD); emotional insecurity (unpredictability of environment eg, alcoholic or bipolar
parent) can lead to panic disorder; cumulative stress over time can lead to panic attacks; biologic causes—
hereditary vulnerability brought out by cumulative stress, fight-or-flight response, noradrenergic, γ-amino butyric
acid (GABA), and serotonin hypotheses (OCD caused by insufficient serotonin in brain); medical
conditions— hyperventilation syndrome, hypoglycemia, hyperthyroidism, mitral valve prolapse; fluctuating
hormones—around time of puberty, premenstrual syndrome, polycystic ovary syndrome, infertility, postpartum,
and perimenopause; short-term triggering causes—stressors precipitating panic attacks, eg, significant personal
loss, life change, stimulants and recreational drugs; phobias—conditioning by trauma or association, eg, bees
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| Treatment: reversing maintaining conditions core of cognitive behavioral therapy (CBT); maintaining conditions
include avoidance of phobic situations, anxious self-talk, mistaken beliefs, withheld feelings, lack of assertiveness,
lack of self-nurturing skills, muscle tension, stimulants, and high-stress lifestyle; patient’s motivation and
commitment essential to recovery; patient needs to define goals and see self as key ingredient in recovery; patient
must change view that world is creating their anxiety; must be willing to give up secondary gain; must have
commitment to discipline and willingness to take risks; takes ≈1 yr to reverse conditioned responses; CBT to be
practiced—deep relaxation technique, vigorous exercise, good nutritional habits, and countering negative self-
talk; imagery desensitization and real-life desensitization 3 to 5 times weekly if patient has phobias
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| Conclusion: anxiety originates in childhood and adolescence; considered problem when it disturbs work, play,
sleep, eating, or social interaction; right-brain phenomena; images feed anxiety and heal fears; can be reversed
or lessened by psychotherapy; anxiety disorders must be taken seriously by health care providers; life stages in
which person vulnerable to anxiety—in childhood, lack of trust or competency can be instilled; in adolescence,
self-esteem can suffer, and patients may feel they do not belong; in young adult years, if not successful in finding
meaningful relationship or vocation; child-rearing and infertility can cause anxiety; in middle years, if mental
and physical health not attended to on regular basis; in later years, if one has not found meaning in life and
has no meaningful relationship
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Educational Objectives
| The goal of this program is to educate the listener about the role of stress in irritable bowel syndrome (IBS) and the
identification of patients with anxiety. After hearing and assimilating this program, the clinician will be better able
to:
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| 1. Clinically diagnose patients with IBS.
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| 2. Establish management plans, including medical and nonmedical options for treatment of patients with IBS.
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| 3. Discuss pathophysiology and the role of stress in the etiology of IBS.
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| 4. Identify patients with generalized anxiety disorder or posttraumatic stress disorder (PTSD).
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| 5. Discuss the causes and nonpharmacologic treatment of anxiety disorders.
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Discussed on This Program
Alosetron HCl [Lotronex]
Citalopram HBr [Celexa]
Dicyclomine HCl [Antispas, Bentyl, Byclomine, Dibent, Dilomine, Di-Spaz, Or-Tyl]
Atropine sulfate, scopolamine HBr, hyoscyamine HBr or sulfate [Barbidonna, Barbidonna No. 2, Donnatal,
Hyosophen, Spasmolin]
Hyoscyamine sulfate (L -hyoscyamine sulfate) [several trade names]
Tegaserod maleate [Zelnorm]
Suggested Reading
Brawman-Mintzer O et al: New trends in the treatment of anxiety disorders. CNS Spectr 9(8 Suppl 7):19, 2004;
Creed F et al: Does psychological treatment help only those patients with severe irritable bowel syndrome who
also have a concurrent psychiatric disorder? Aust NZJ Psychiatry 39(9):807, 2005; Fricchione G: Clinical practice.
Generalized anxiety disorder. N Engl J Med 351(7):675, 2004; Gilkin RJ Jr: The spectrum of irritable bowel syndrome:
A clinical review. Clin Ther 27(11):1696, 2005; Harris LA et al: Irritable bowel syndrome: new and emerging
therapies. Curr Opin Gastroenterol 22(2):128, 2006; Jackson JL et al: Treatment of functional gastrointestinal
disorders with antidepressant medications: a meta-analysis. Am J Med 108(1):65, 2000; Kane S: Gender issues in
the management of irritable bowel syndrome. Int J Fertil Womens Med 50(2):79, 2005; Keller MB et al: Untangling
depression and anxiety: clinical challenges. J Clin Psychiatry 66(11):1477, 2005; Lang AJ: Treating generalized
anxiety disorder with cognitive-behavioral therapy. J Clin Psychiatry 65 Suppl 13:14, 2004; Mach T: The brain-gut
axis in irritable bowel syndrome—clinical aspects. Med Sci Monit 10(6):RA125, 2004; North CS et al: The presentation
of irritable bowel syndrome in the context of somatization disorder. Clin Gastroenterol Hepatol 2(9):787,
2004; Rapaport MH: Prevalence, recognition, and treatment of comorbid depression and anxiety. J Clin Psychiatry
62 Suppl 24:6, 2001; Toner BB: Cognitive-behavioral treatment of irritable bowel syndrome. CNS Spectr
10(11):883, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant
financial relationship with the manufacturer or provider of any commercial product or service discussed. For this
issue, the faculty reported nothing to disclose.
Dr. Weisiger was recorded at Controversies in Women’s Health, sponsored by the University of California, San Francisco,
School of Medicine, held on December 8-9, 2005 in San Francisco. Dr. Gerber was recorded at Women’s
Health Issues: Perception, Prevention & Practice, sponsored by the University of Vermont College of Medicine, held
on May 12-14, 2005 in South Burlington, Vermont. The Audio-Digest Foundation thanks the speakers and the
sponsors for their cooperation in the production of this program.
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