Duloxetine in Inflammatory Bowel Diseases

A Phase II Open-label Study of Duloxetine to Reduce Inflammatory Bowel Disease-Related Disability and Psychological Distress

This open-label, prospective, single-arm pilot study investigates the use of duloxetine, a central neuromodulator, for improving psychological distress and functional impairment in adults with inflammatory bowel disease (IBD). The study focuses on patient-reported outcomes related to anxiety, depression, and IBD-related disability, aiming to assess feasibility, tolerability, and preliminary efficacy in modulating gut-brain axis symptoms and disease-related functional impairments in life

Subjects will be screened and enrolled once PI confirms eligibility. After patient signs consent:

Duloxetine 30 mg orally daily will be administered for 1 week (age <65 years) or 2 weeks (age ≥65 years), then increased to duloxetine 60 mg orally daily, if tolerated.

Patients may continue duloxetine 30 mg if they do not tolerate duloxetine 60 mg.

Patients will receive 30-60 mg of duloxetine for 6 weeks, followed by a tapering period of 2 weeks at the end of treatment, mailed to their home address. Patients who wish to continue taking duloxetine after the trial may contact their primary care provider to obtain a prescription for duloxetine.

Patient reported outcomes will be completed at set intervals.

Inclusion Criteria:

• Adults over 24 years old; (younger patients are excluded because antidepressants have been shown to increase the risk of suicidal thinking and behavior in patients ≤ 24 years old.)

• At least one of the following:

  1. elevated psychological distress (Distress Thermometer score > 4),10-12
  2. moderate-to-severe IBD-related disability (IBD-DI score ≥ 356, 7), or
  3. elevated GI-specific anxiety (Visceral Sensitivity Index > 10) -

Exclusion Criteria:

• Concomitant use of antidepressants (including serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, buspirone, and thioridazine).
• Initiation of psychotherapy within 8 weeks.
• Inability or unwillingness to monitor ambulatory blood pressure and receive a blood pressure monitor via postal mail.
• Cirrhosis with clinically evident hepatic insufficiency (Child-Pugh Class B or C) by medical record review.1
• Severe renal impairment (on dialysis; chronic kidney disease stage 4-5; acute kidney injury with glomerular filtration rate <30 mL/minute) by medical record review of labs performed within 18 months.
• Concurrent participation in another clinical trial of an investigational medicinal product.
• Pregnant or lactating either by self-report or medical record review
• Glaucoma
• Gastroparesis
• Use of medications that could lead to serious interactions with the study medication: potent CYP1A2 inhibitors, antidepressants (including serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, buspirone, thioridazine), linezolid, intravenous methylene blue, triptans, lithium, fentanyl, tramadol, meperidine, methadone, tryptophan, amphetamines, and St. John's Wort.
• Bipolar, psychotic, alcohol use disorder, non-alcohol substance-induced disorders, or imminent danger to self or others