Open Trial of Duloxetine in Outpatients With Irritable Bowel Syndrome Symptoms and Co-Morbid Major Depression

This study is a 12-week open trial to assess the efficacy of duloxetine (Cymbalta) for the
treatment of Irritable Bowel Syndrome (IBS) symptoms and comorbid Major Depressive Disorder
(MDD).

Participants will visit the clinic 8 times to meet with the psychiatrist. They will receive
duloxetine to see if it helps their major depression and Irritable Bowel symptoms. Upon
study completion at 12 weeks, they will receive an additional 3 months of free medication
treatment at our clinic.

Inclusion Criteria:

- Meets Diagnostic and Statistical Manual,Fourth Edition (DSM-IV) criteria for major
depressive disorder (MDD)

- Meets sufficient Rome III criteria for clinical symptoms of IBS

- Able to give consent

- Fluency in English or Spanish

- Patients ages 50-65 must provide a negative colonoscopy report

Exclusion Criteria:

- Current suicide risk

- History of psychosis, bipolar disorder, or a current diagnosis of
Obsessive-Compulsive Disorder (OCD)

- History of alcohol or other substance abuse or dependence in the six months prior to
the study

- History of non-response to an adequate trial of duloxetine

- Require concurrent treatment with other psychotropic medication or other psychiatric
treatment, except zolpidem for insomnia

- Receive current treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of
visit 1 or potential need to use an MAOI during the study or within 5 days of
discontinuation of study drug

- Patients with uncontrolled narrow-angle glaucoma

- Received electroconvulsive therapy (ECT) during the last three months

- Unable to tolerate or unwillingness to accept drug-free period of varying length: 1
week for Pro Re Nata (PRN) benzodiazepines; 2 weeks for antidepressants (other than
fluoxetine), buspirone, lithium, anticonvulsants, stimulants, barbiturates, opiates,
regular-use benzodiazepines (except clonazepam); 5 weeks for clonazepam and
fluoxetine

- Clinically unstable medical disease including: Systemic hypertension of 140/90 mm Hg
or more; known hypersensitivity to duloxetine or any of its inactive ingredients;
liver function test values three times above the normal level; clinically significant
thyroid dysfunction, (except patients who are stable on thyroid replacement therapy
for at least three months)

- History of chronic, persisting vomiting; rectal bleeding (melena, hematochezia,
Bright Red Blood Per Rectum); severe, continuous abdominal pain; nocturnal awakening
with GI symptoms; weight loss not clearly related to decreased appetite of MDD;
incapacitating symptoms of IBS; severe Upper GI symptoms (e.g., heartburn) that
interrupt daily activities

- Family history of Ulcerative Colitis, Crohn's Disease, Celiac Disease or Colon Cancer

- Clinical findings on Physical Exam or laboratory tests of: Rectal
bleeding/obstruction, elevated White Blood Cell (WBC) count, unexplained anemia,
abnormal Erythrocyte Sedimentation Rate (ESR), abnormal celiac disease panel

- Evidence of clinically significant renal, pulmonary, cerebral vascular,
cardiovascular, endocrine disorders, prostatic hypertrophy, urinary retention,
laboratory abnormalities, abnormal electrocardiogram

- Cancer of any type. Patients in remission for 5 years or more may be judged
acceptable

- Patients with current or past history of seizure disorder (except febrile seizure in
childhood)

- Patients who are pregnant, breast-feeding or who do not use adequate contraceptive
methods. Adequate methods include birth control pills, condom plus spermicide, an
intrauterine device, the Norplant system, or diaphragm.

- Patients who are receiving effective medication for their depression or their IBS
symptoms. Patients on effective medication for either disorder will be excluded.

- Patients on antidepressants and/or anti-IBS medications at intake must still meet
inclusion criteria after receiving 3 months or more of medication that was dosed
following FDA guidelines. Doses must have been raised so as to produce either
intolerable side effects or treatment response.

- Patients who require treatment with thioridazine for any reason, at baseline and
throughout the study.