Fluoxetine for Refractory Constipation

• Fluoxetine (Drug), also known as polyethylene glycol: 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).
• Polyethylene Glycol 400 0.4% (Drug): The control group (PEG) used polyethylene glycol as a rescue medication under the same conditions, following similar monitoring and follow-up procedures.

Primary outcomes

• Proportion of patients with a CSBM of 3 or more per week [baseline, six months after treatment]: 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.

Secondary outcomes

• 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]

Sex: All, ages: 18 Years to 70 Years

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.