Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder
characterized primarily by abdominal pain associated with bowel dysfunction. Like many
other painful functional somatic syndromes (e.g. fibromyalgia) the pathophysiology of IBS
includes abnormal responses to pain and dysregulation of brain-body pain pathways. IBS
affects up to 10% of the population, is a leading reason for visits to gastroenterologists
and primary care doctors, and, in the United States, annually accrues health care costs over
$20 billion.

In their practice the investigators use centrally acting agents to treat IBS. Historically,
the investigators have used tricyclic antidepressants based on results of clinical trials,
including our NIH funded trial on desipramine. Nonetheless, these agents can produce side
effects that limit their full application. More recently the investigators have begun to use
SNRIs because they have been shown to benefit for various pain syndromes like diabetic
neuropathy, fibromyalgia. The initial impression is that Milnacipran helps improve IBS
symptoms and global well being. There is now a need to systematically determine
Milnacipran's value for IBS.

Inclusion Criteria:

- Meet Rome III criteria for IBS and have no red flags.

- Must have had a colonoscopy within the previous 5 years to exclude inflammatory or
other bowel disease

- Be fluent and literate in English

- Must either be of non-childbearing potential or agree to utilize approved birth
control for the duration of the study

Exclusion Criteria:

- Diagnosis or treatment of any clinically symptomatic biochemical or structural
abnormality of the GI tract within 6 months prior to screening, or active disease
within 6 months prior to screening.

- Any other diagnosis to explain the abdominal pain,

- Clinical evidence of significant cardiovascular, respiratory, renal, hepatic,
gastrointestinal, hematologic, neurologic, psychiatric or any disease that may
interfere with the subject successfully completing the trial

- Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >3 times the upper limit of normal) or
renal impairment (serum creatinine > 2mg/dL)

- Has disease affecting electrolytes balance, such as SIADH with serum Sodium less than
130mmol/L

- Any evidence of or treatment of malignancy (other than localized basal cell, squamous
cell skin cancer or cancer in situ that has been resected) within the previous year

- Any surgery on the stomach, small intestine or colon, excluding appendectomy

- A major psychiatric disorder (DSM-III-R or DSM-IV) including major depression or
other psychoses that has required hospitalization in the last 1 year.

- History of attempted suicide or uncontrolled bipolar disorder.

- Currently using antidepressants for psychiatric conditions like major depression. Use
of TCA or SSRI class antidepressant acceptable if being used specifically for
treatment of bowel symptoms and patient is willing to taper off the medication

- Previous use of Milnacipran or other SNRI antidepressant (duloxetine, venlafaxine,
desvenlafaxine)

- A diagnosis of seizure disorder

- A diagnosis of glaucoma

- Currently taking heparin or warfarin