Adding Amantadine or Duloxetine to Pregabalin on Occurrence of Post Mastectomy Pain Syndrome

The Effect of Adding Amantadine or Duloxetine to Pregabalin on Occurrence of Post Mastectomy Pain Syndrome; Randomized Controlled Study

This study aims to evaluate the additive effect of Amantadine or Duloxetine to Pregabalin on development of post mastectomy pain syndrome

Study Overview

• Status: Recruiting
• Conditions: Mastectomy; Pain Syndrome; Pregabalin; Amantadine; Duloxetine
• Intervention / Treatment: Drug: Pregabalin; Drug: Pregabalin + Amantadine; Drug: Pregabalin + Duloxetine

Detailed Description

Post mastectomy pain syndrome (PMPS) is considered one of the most common types of CPSP with incidence ranging between 20% - 50%.

Pregabalin is one of the drugs that can reduce the excitability of the dorsal horn neurons. It is a γ-aminobutyric acid analogue that binds to α2-δ subunits of the voltage-gated calcium channels in the central nervous system.

Duloxetine is an SNRI that increases serotonin and norepinephrine levels in the central nervous system, which helps modulate pain pathways. Originally developed for depression and anxiety, it is also used for chronic pain conditions such as fibromyalgia, diabetic neuropathy, and chronic musculoskeletal pain.

Amantadine is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors. These receptors play a significant role in the development of central sensitization, acute opioid tolerance, and opioid-induced hyperalgesia.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hossam H Sayed, MSc; Phone Number: 00201144692302; Email: hussamhassan90@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt, 12613
    • Recruiting
    • Cairo University
    • Sub-Investigator: Raafat M Reyad, MD
    • Contact: Hossam H Sayed, MSc; Phone Number: 00201144692302; Email: hussamhassan90@gmail.com
    • Sub-Investigator: Reham M Gamal, MD
    • Sub-Investigator: Salma Abd Elmooty, MD
    • Sub-Investigator: Ahmed S Mohammed, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age from 18 to 65 years.
• American society of anesthesiologists (ASA) Physical status II, III.
• Body mass index (BMI): (20-40) kg/m2.
• Type of surgery: patients undergoing modified radical mastectomy for breast cancer.

Exclusion Criteria:

• Patient refusal.
• Patients with Known sensitivity or contraindication to drug used in the study.
• History of psychological disorders and/or chronic pain and drug abuse patients.
• Previous administration of antidepressants, anticonvulsants, or opioids before surgery.
• Severe respiratory or cardiac disorders.
• Advanced liver or kidney disease.
• Previous breast surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group P (Pregabalin group); Two hours preoperative patient will receive one capsule of Pregabalin 75 mg (Lyrica 75 mg, Viatris) and) and one placebo tablet and will continue on both of them twice daily for seven days postoperative.	Drug: Pregabalin; Two hours preoperative patient will receive one capsule of Pregabalin 75 mg (Lyrica 75 mg, Viatris) and) and one placebo tablet and will continue on both of them twice daily for seven days postoperative
Experimental: Group PA (Pregabalin + Amantadine group); Two hours preoperative patient will receive one capsule of pregabalin 75 mg (Lyrica 75 mg, Viatris) and one tablet of Amantadine 100 mg (PK-Merz 100 mg, MERZ Pharma) and will continue on both twice daily for seven days postoperative.	Drug: Pregabalin + Amantadine; Two hours preoperative patient will receive one capsule of pregabalin 75 mg (Lyrica 75 mg, Viatris) and one tablet of Amantadine 100 mg (PK-Merz 100 mg, MERZ Pharma) and will continue on both twice daily for seven days postoperative.
Experimental: Group PD (Pregabalin + Duloxetine group); Two hours preoperative patient will receive one capsule of pregabalin 75 mg (Lyrica 75 mg, Viatris) and one capsule of Duloxetine 30 mg (Cymbatex 30 mg, EVA Pharma) and will continue on both twice daily for seven days postoperative.	Drug: Pregabalin + Duloxetine; Two hours preoperative patient will receive one capsule of pregabalin 75 mg (Lyrica 75 mg, Viatris) and one capsule of Duloxetine 30 mg (Cymbatex 30 mg, EVA Pharma) and will continue on both twice daily for seven days postoperative.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of occurrence of post mastectomy pain syndrome	The rate of occurrence of post mastectomy pain syndrome will be recorded according to Grading system for neuropathic pain (GSNP). GSNP is as follows: Grade 1 (unlikely), Grade 2 (possible), Grade 3 (probable), and Grade 4 (definite), the patients will be considered positive regarding incidence being in grade 3 or 4.	12 weeks post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Quality of life	Patient's Quality of life will be assessed using Flanagan Quality of Life Scale (QOLS) which is a 16-item (domain) questionnaire with each item scored from 1 to 7 points. The scale will be explained to the patients and the total score will be calculated and recorded at the preoperative assessment (baseline) and at postoperative weeks 2, 4, 8,12.	12 weeks post-procedure
Patient's activity level	Postoperative patient's activity level will be assessed using Barthel Activities of Daily Living scale (ADL). This scale comprises 10 basic daily activities (bowel, bladder, feeding, toilet, bathing, dressing, grooming, walking, stairs and transfer) with each item scored as 0 = need complete help, 1 = need some help or 2 = need no help.	12 weeks post-procedure
Degree of pain	Each patient will be instructed about postoperative pain assessment with the numeric rating scale (NRS). NRS (0 represents "no pain" while 10 represents "the worst pain imaginable").	12 weeks post-procedure
Total amount of fentanyl	Total amount of fentanyl consumed intraoperative will be recorded.	Intraoperatively
Total amount of morphine consumption	Rescue analgesia will be provided in the form of IV morphine 3 mg boluses if the patient indicates numeric rating scale (NRS)≥ 4.	48 hours post-procedure
Incidence of side effects related to Pregabalin	Incidence of side effects related to Pregabalin such as headaches, feeling sleepy, tired or dizzy, diarrhea, mood changes, swollen hands, arms, legs and feet, blurred vision, erectile dysfunction, weight gain, and memory problems will be recorded.	48 hours post-procedure
Incidence of side effects related to Amantadine	Incidence of side effects related to Amantadine such as dry mouth, constipation, nausea, vomiting, decreased appetite, difficulty falling asleep or staying asleep, abnormal dreams, headache, confusion, drowsiness, tiredness, uncontrollable tightening of muscles, and lace-like purple pattern on skin will be recorded.	48 hours post-procedure
Incidence of side effects related to duloxetine	Incidence of side effects related to duloxetine such as dry mouth, constipation, loss of appetite, fatigue, drowsiness, or increased sweating. Some people may experience dizziness, headache, or insomnia will be recoded.	48 hours post-procedure

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 21, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Somatoform Disorders; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Adamantane; Bridged-Ring Compounds; Thiophenes; Duloxetine Hydrochloride; Pregabalin; Amantadine
• Other Study ID Numbers: AP2511-201-211-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be available upon a reasonable request from the corresponding author after the end of study for one year.
• IPD Sharing Time Frame: After the end of study for one year.
• IPD Sharing Access Criteria: The data will be available upon a reasonable request from the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No