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

Study Overview
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Brief Summary
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This study will evaluate the efficacy of duloxetine in reducing depressive symptoms, abdominal pain, and other symptoms of Irritable Bowel Syndrome (IRS) in a population of outpatients with Major Depressive Disorder MDD and clinical symptoms of IBS.

Detailed Description
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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.

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

Conditions
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Major Depression, Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Duloxetine<br>Patients will receive open treatment with Duloxetine | Drug: Duloxetine<br>* 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.<br>* Other names: Cymbalta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) | Clinician-administered 10-item scale measuring depressive symptoms (range 0-60); higher scores indicate greater severity of major depression. | Weeks 0, 8, 12 | 
| Gastrointestinal Symptoms Rating Scale (GSRS) | Clinician-administered 15-item scale measuring IBS symptoms (range 15-105); higher score indicates greater IBS severity. | Weeks 0, 8, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician-Rated Global Impression Scales (CGI) | Two clinician-administered scales measuring level of change in (1) depressive symptoms and (2) IBS symptoms, assessed separately. Range is 1-7, ranging from very much improved (1) to very much worsened (7). | Measured at weeks 0, 8, 12 | 
| Visual Analogue Scales (VAS) | Five self-report 11-point Likert scales measuring pain severity in the following domains (one item each): overall pain, pain interfering with daily activities, headaches, back pain, and shoulder pain. Range is 0-10; higher scores indicate higher pain severity. | Measured at weeks 0, 8, 12 | 
| Somatization Module of the Patient's Health Questionnaire (PHQ-15) | Self-report 15-item scale measuring somatization symptoms (range 0-30); higher score indicates greater severity of somatization symptoms. | Measured at weeks 0, 8, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depression, Irritable Bowel Syndrome, Somatization, Cymbalta, Duloxetine