Fluoxetine for Refractory Constipation

The Safety and Efficacy of Fluoxetine for Treatment of Refractory Constipation

The goal of this clinical trial is to learn if fluoxetine works to treat refractory constipation . It will also learn about the safety of fluoxetine. The main questions it aims to answer are:

Does fluoxetine increase the number of completely spontaneous bowel movements (CSBMs) per week? What medical problems do participants have when taking fluoxetine? Does fluoxetine improve psychological symptoms such as anxiety and depression in participants with refractory constipation? Researchers will compare fluoxetine to polyethylene glycol (PEG, a commonly used laxative) to see if fluoxetine works to treat refractory constipation.

Participants will:

Take fluoxetine (40 mg/day) or polyethylene glycol (once daily) for 6 months. Visit the clinic at baseline, and at 1 month, 3 months, and 6 months for checkups and tests.

Record their bowel movements and any changes in symptoms, including anxiety, depression, and side effects.

Study Overview

• Status: Completed
• Conditions: Refractory Constipation
• Intervention / Treatment: Drug: Fluoxetine; Drug: Polyethylene Glycol 400 0.4%

• Study Type: Interventional
• Enrollment (Actual): 316
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Ningxia
    • Yinchuan, Ningxia, China, 750011
      • People's Hospital of Ningxia Hui Autonomous Region
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • The First Affiliated Hospital of the Fourth Military Medical University
    • Xi'an, Shaanxi, China, 710032
      • Xi'an International Medical Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. individuals aged 18 to 70 years;
2. patients meeting the Rome IV diagnostic criteria for chronic constipation, defined by at least two symptoms: straining, lumpy or hard stools (Bristol Stool Scale types 1-2), incomplete evacuation, anorectal obstruction, need for manual maneuvers, or spontaneous bowel movements occurring less than three times per week. These symptoms must have persisted for a minimum of six months, with the diagnostic criteria being met for at least the past three months;
3. refractory constipation, defined as the use of at least three medications (including osmotic agents, laxatives, prokinetics, biofeedback and probiotics, surgery) for more than three months, with unsatisfactory treatment outcomes;
4. patients present indications for fluoxetine, such as comorbid depression;
5. patients who voluntarily provided informed consent prior to enrollment.

Exclusion Criteria:

1. women who are pregnant or lactating;
2. presence of cardiovascular conditions, organ dysfunction, immune disorders, or infections;
3. concurrent gastrointestinal organic conditions such as tuberculosis, polyps, Crohn's disease, tumors, etc.;
4. prior abdominal surgeries;
5. use of psychotropic medications; 6) diagnosis of hypothyroidism or Parkinson's disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluoxetine Treatment Group; Patients in the fluoxetine group received oral fluoxetine starting at 40 mg/day for six months. The dose could be increased to 60 mg/day if symptoms persisted or reduced if mild adverse effects (e.g., dizziness, nausea, tremors) occurred. Treatment was discontinued if serious adverse reactions developed or if no improvement was observed after dose escalation. Compliance and treatment progress were monitored via telephone follow-ups. For patients unable to have a bowel movement for three consecutive days or experiencing intolerable symptoms, polyethylene glycol (PEG, 10 g) was provided as rescue medication. Bowel movements within 24 hours of rescue medication use were excluded from the count of complete spontaneous bowel movements (CSBM).	Drug: Fluoxetine; Patients in the fluoxetine group received oral fluoxetine starting at 40 mg/day for six months. Treatment was discontinued if serious adverse reactions developed or if no improvement was observed after dose escalation. Compliance and treatment progress were monitored via telephone follow-ups. For patients unable to have a bowel movement for three consecutive days or experiencing intolerable symptoms, polyethylene glycol (PEG, 10 g) was provided as rescue medication. Bowel movements within 24 hours of rescue medication use were excluded from the count of complete spontaneous bowel movements (CSBM).; Other Names: polyethylene glycol
Active Comparator: PEG Treatment Group; The control group (PEG) used polyethylene glycol as a rescue medication under the same conditions, following similar monitoring and follow-up procedures.	Drug: Polyethylene Glycol 400 0.4%; The control group (PEG) used polyethylene glycol as a rescue medication under the same conditions, following similar monitoring and follow-up procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a CSBM of 3 or more per week	The primary endpoint of this study is the proportion of patients achieving a weekly frequency of three or more complete spontaneous bowel movements (CSBMs) after six months of treatment. A CSBM is defined as a bowel movement that occurs without the use of rescue medication (e.g., polyethylene glycol) within the preceding 24 hours. This endpoint aims to evaluate the efficacy of fluoxetine in improving bowel function in patients with refractory constipation as compared to the control group.	baseline, six months after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean number of spontaneous bowel movements (SBMs) per week	baseline, 1 month, 3 months, 6 months
Mean number of complete spontaneous bowel movements (CSBMs) per week	baseline, 1 month, 3 months, 6 months
Stool consistency (Bristol Stool Form Scale, BSFS, scores of 3-5)	baseline, 1 month, 3 months, 6 months

Collaborators and Investigators

• Sponsor: Zhifeng Zhao, PhD

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): May 30, 2025

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: XJLL-KY20222069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No