Irritable Bowel Syndrome, Major Depression
Conditions
Keywords
Major Depression, Irritable Bowel Syndrome, Somatization, Cymbalta, Duloxetine
Brief summary
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
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.
Interventions
DRUGDuloxetine
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.
Sponsors
Eli Lilly and Company
New York State Psychiatric Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | Weeks 0, 8, 12 | Clinician-administered 10-item scale measuring depressive symptoms (range 0-60); higher scores indicate greater severity of major depression. |
| Gastrointestinal Symptoms Rating Scale (GSRS) | Weeks 0, 8, 12 | Clinician-administered 15-item scale measuring IBS symptoms (range 15-105); higher score indicates greater IBS severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Rated Global Impression Scales (CGI) | Measured at weeks 0, 8, 12 | 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). |
| Visual Analogue Scales (VAS) | Measured at weeks 0, 8, 12 | 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. |
| Somatization Module of the Patient's Health Questionnaire (PHQ-15) | Measured at weeks 0, 8, 12 | Self-report 15-item scale measuring somatization symptoms (range 0-30); higher score indicates greater severity of somatization symptoms. |
Countries
United States
Participant flow
Recruitment details
Study participants were recruited through print and electronic advertisements (n=12). We also received referrals from community clinicians (n=3), a former patient (n=1) and a psychiatric help line (n=1). Recruitment took place from 1/19/07 to 5/20/14.
Pre-assignment details
This study was a single-arm open trial, so all the participants were assigned to the open-label duloxetine treatment arm.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Duloxetine Patients will receive open treatment with Duloxetine
Duloxetine: 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. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Moved out of town | 1 |
| Overall Study | Scheduling conflict | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment With Duloxetine |
|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Gastrointestinal Symptoms Rating Scale (GSRS)
Clinician-administered 15-item scale measuring IBS symptoms (range 15-105); higher score indicates greater IBS severity.
Time frame: Weeks 0, 8, 12
Population: Sample size decreased due to attrition over course of study, N=17 at Week 0, N=12 at Week 8, N=10 at Week 12. Our primary analysis was a repeated measures mixed-methods regression that included all available data points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Duloxetine | Gastrointestinal Symptoms Rating Scale (GSRS) | Week 0 | 54.76 units on a scale | Standard Deviation 15.45 |
| Treatment With Duloxetine | Gastrointestinal Symptoms Rating Scale (GSRS) | Week 8 | 36.33 units on a scale | Standard Deviation 13.93 |
| Treatment With Duloxetine | Gastrointestinal Symptoms Rating Scale (GSRS) | Week 12 | 31.4 units on a scale | Standard Deviation 12.27 |
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in total GSRS symptom scores for IBS. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (wks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-27.44, -13.97]Mixed Models Analysis
Primary
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.
Time frame: Weeks 0, 8, 12
Population: Sample size decreased due to attrition over course of study, N=17 at Week 0, N=12 at Week 8, N=10 at Week 12. Our primary analysis was a repeated measures mixed-methods regression that included all available data points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Duloxetine | Montgomery-Asberg Depression Rating Scale (MADRS) | Week 0 | 31.59 units on a scale | Standard Deviation 8.46 |
| Treatment With Duloxetine | Montgomery-Asberg Depression Rating Scale (MADRS) | Week 8 | 15.67 units on a scale | Standard Deviation 11.39 |
| Treatment With Duloxetine | Montgomery-Asberg Depression Rating Scale (MADRS) | Week 12 | 11.4 units on a scale | Standard Deviation 6.7 |
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in total MADRS symptom scores for MDD. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (wks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-23.44, -12.63]Mixed Models Analysis
Secondary
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).
Time frame: Measured at weeks 0, 8, 12
Population: Sample size decreased due to attrition over course of study, N=17 at Week 0, N=12 at Week 8, N=10 at Week 12. Our primary analysis was a repeated measures mixed-methods regression that included all available data points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Duloxetine | Clinician-Rated Global Impression Scales (CGI) | CGI - Major Depression, Week 0 | 4.71 units on a scale | Standard Deviation 0.85 |
| Treatment With Duloxetine | Clinician-Rated Global Impression Scales (CGI) | CGI - Major Depression, Week 8 | 3.58 units on a scale | Standard Deviation 0.67 |
| Treatment With Duloxetine | Clinician-Rated Global Impression Scales (CGI) | CGI - Major Depression, Week 12 | 3 units on a scale | Standard Deviation 0.94 |
| Treatment With Duloxetine | Clinician-Rated Global Impression Scales (CGI) | CGI - IBS, Week 0 | 4.65 units on a scale | Standard Deviation 0.7 |
| Treatment With Duloxetine | Clinician-Rated Global Impression Scales (CGI) | CGI - IBS, Week 8 | 3.58 units on a scale | Standard Deviation 0.67 |
| Treatment With Duloxetine | Clinician-Rated Global Impression Scales (CGI) | CGI - IBS, Week 12 | 3 units on a scale | Standard Deviation 0.94 |
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in CGI-MDD score. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-2.16, -1.03]Mixed Models Analysis
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in CGI-IBS score. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-1.99, -1.11]Mixed Models Analysis
Secondary
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.
Time frame: Measured at weeks 0, 8, 12
Population: Sample size decreased due to attrition over course of study, N=17 at Week 0, N=12 at Week 8, N=10 at Week 12. Our primary analysis was a repeated measures mixed-methods regression that included all available data points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Duloxetine | Somatization Module of the Patient's Health Questionnaire (PHQ-15) | Week 0 | 16.06 units on a scale | Standard Deviation 3.75 |
| Treatment With Duloxetine | Somatization Module of the Patient's Health Questionnaire (PHQ-15) | Week 8 | 12.87 units on a scale | Standard Deviation 4.26 |
| Treatment With Duloxetine | Somatization Module of the Patient's Health Questionnaire (PHQ-15) | Week 12 | 11.1 units on a scale | Standard Deviation 6 |
Comparison: We used the intention-to-treat (ITT) sample with all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in PHQ-15 scores of somatization symptoms. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-7.39, -1.36]Mixed Models Analysis
Secondary
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.
Time frame: Measured at weeks 0, 8, 12
Population: Sample size decreased due to attrition over course of study, N=17 at Week 0, N=12 at Week 8, N=10 at Week 12. Our primary analysis was a repeated measures mixed-methods regression that included all available data points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Overall pain, Week 0 | 5 units on a scale | Standard Deviation 2.62 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Pain interfering with daily activities, Week 0 | 4.94 units on a scale | Standard Deviation 3.42 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Headaches, Week 0 | 4.24 units on a scale | Standard Deviation 2.19 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Back pain, Week 0 | 5.47 units on a scale | Standard Deviation 2.62 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Shoulder pain, Week 0 | 5.29 units on a scale | Standard Deviation 3.21 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Overall pain, Week 8 | 6.08 units on a scale | Standard Deviation 2.11 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Pain interfering with daily activities, Week 8 | 6 units on a scale | Standard Deviation 2.7 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Headaches, Week 8 | 4.5 units on a scale | Standard Deviation 2.97 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Back pain, Week 8 | 5.58 units on a scale | Standard Deviation 3 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Shoulder pain, Week 8 | 5.17 units on a scale | Standard Deviation 3.07 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Overall pain, Week 12 | 4.1 units on a scale | Standard Deviation 3 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Pain interfering with daily activities, Week 12 | 4.8 units on a scale | Standard Deviation 3.01 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Headaches, Week 12 | 3.4 units on a scale | Standard Deviation 2.63 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Back pain, Week 12 | 4.9 units on a scale | Standard Deviation 3.03 |
| Treatment With Duloxetine | Visual Analogue Scales (VAS) | Shoulder pain, Week 12 | 4.7 units on a scale | Standard Deviation 3.3 |
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in VAS score of overall pain. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-1.16, 1.1]Mixed Models Analysis
Comparison: We used the intention-to-treat (ITT) sample with all subjects dispensed medication (n=17). This repeated-measures mixed-effects regression analysis assessed the rate of change in VAS score of pain interfering with daily activities. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a 1st-order autocorrelation structure. Data from each time point (wks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysisp-value: <0.0595% CI: [-1.07, 2.01]Mixed Models Analysis
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in VAS score of headaches. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-2.28, 1.1]Mixed Models Analysis
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in VAS score of back pain. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-1.56, 0.87]Mixed Models Analysis
Comparison: We used the intention-to-treat (ITT) sample, including all subjects dispensed medication (n=17). This was a repeated-measures mixed-effects regression analysis assessing the rate of change in VAS score of shoulder pain. To account for the correlation of observations within individuals, we used mixed-effects models with random intercepts and a first-order autocorrelation structure. Data from each time point (weeks 0, 1, 2, 3, 4, 6, 8, 12) were used in the single repeated-measures analysis.p-value: <0.0595% CI: [-2, 1.03]Mixed Models Analysis