The Efficacy and Safety of Short Term S-ketamine Infusion as an Adjunctive Therapy in Patients With Fibromyalgia

Comparing the Efficacy and Safety of Conventional Therapy With Conventional Therapy Combined Esketamine in the Treatment of Fibromyalgia: A Multicenter Clinical Study

Fibromyalgia is a chronic pain syndrome where current medications have limited efficacy and a slow onset of action. Esketamine shows potential as a rapid-acting analgesic, but previous low-dose studies failed to demonstrate long-term benefits. The efficacy of higher-dose ESK as an adjunctive therapy when standard treatments are insufficient remains unclear.

Study Overview

• Status: Recruiting
• Conditions: Fibromyalgia; Pregabalin; Esketamine
• Intervention / Treatment: Drug: Pregabalin and venlafaxine concomitant therapy; Drug: Esketamine plus pregabalin and venlafaxine concomitant therapy

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fang Luo; Phone Number: +8613611326978; Email: 15383510462@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital, Beijing, Beijing 100070
    • Contact: Fang Luo; Phone Number: +8613611326978; Email: 13611326978@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients between ages over 18 years with proper cognitive function and language skills for the study;
• Patients diagnosed with FM as defined by the ACR FM diagnostic criteria;
• Patients who have experienced insufficient symptom relief with non-pharmacological treatments and have not previously received recommended pharmacological treatment for FM;
• A score of ≥ 4 on the average pain intensity over 7 days on the numeric rating scale (NRS) at baseline.

Exclusion criteria:

• Patient refusal;
• Inability to sign informed consent;
• Had other secondary FM, this is, hypothyroidism, nutritional deficiency, diabetes mellitus, connective tissue disorder;
• Had psychiatric disorder, this is, schizophrenia and other psychotic disorder, bipolar disorder, or personality disorder;
• Obstructive sleep apnea syndrome or a STOP-Bang score ≥ 3;
• History of treatment with pregabalin and/or venlafaxine for any disease;
• History of treatment with intravenous ketamine or ESK for chronic pain;
• Presence of other painful ailments such as inflammatory rheumatic disease;
• Uncontrolled diabetes, refractory hypertension, malignancies, narrow-angle glaucoma, hyperthyroidism, severe cardiovascular disease or any other contraindications to esketamine;
• History of prescription drug abuse, alcoholism or illicit drug use;
• Pregnant or lactating women;
• Allergic to any of the study drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Pregabalin and venlafaxine concomitant therapy	Drug: Pregabalin and venlafaxine concomitant therapy; The control group will only receive an increased dosage of pregabalin and venlafaxine regimen. Each participant will be instructed with the same dose escalation regimen, until they reach the maximal tolerated dose (MTD) or the ceiling dose or the maximum daily recommended dose. The maximum recommended daily dose of pregabalin was 450 mg and venlafaxine was 225 mg.
Experimental: Treatment group; Esketamine plus pregabalin and venlafaxine concomitant therapy	Drug: Esketamine plus pregabalin and venlafaxine concomitant therapy; The treatment group, in addition to the increased pregabalin and venlafaxine medication dosage regimen, will also receive a single intravenous infusion of esketamine on the day of enrollment. Plasma concentrations of esketamine and its metabolites will be measured at the end of infusion to enable a limited characterization of systemic exposure and to support exploratory exposure-response analyses. Each participant will be instructed with the same dose escalation regimen, until they reach the maximal tolerated dose (MTD) or the ceiling dose or the maximum daily recommended dose. The maximum recommended daily dose of pregabalin was 450 mg and venlafaxine was 225 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the mean pain intensity	This outcome is calculated as the average of daily 24-hour pain intensity scores recorded in patient diaries over 7 consecutive days using NRS.	At the week 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average pain intensity	The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable.	At the weeks 1, 2, 4, 8, and 12
Worst pain intensity	The worst pain intensity over the past 24 hours, rated each morning upon awakening and averaged over 7 days. The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable.	at weeks 1, 2, 4, 8, and 12
Proportion of patients achieving pain reduction at 50% and 30%;	The proportion of patients achieving a ≥ 50% and ≥ 30% reduction in mean baseline pain intensity. The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable.	at weeks 1, 2, 4, 8, and 12
The maximal tolerated doses of pregabalin and venlafaxine		at weeks 1, 2, 4, 8, and 12
The Revised FM Impact Questionnaire (FIQR)	The FIQR is used to assessed health status and functional disablity. FIQR is a 21-item self-administered questionnaire, based on symptoms reported within the preceding 7 days. FIQR total score ranges from 0 to 100, with higher values indicating worse health status.	At the weeks 4, 8, and 12
Hospital Anxiety and Depression scale (HADS)	The HADS is used to assess anxiety (7 items) and depression (7 items). Scores range from 0 to 21 on each subscale, with higher scores indicating worse symptomatology.	At the weeks 4, 8, and 12
The short-form 36 Health Survey (SF-36)	The SF-36 assesses health-related quality of life, capturing preferences across various health states. It assesses 8 dimensions: physical functioning, physical role limitations due to physical health, bodily pain, general health, vitality, social functioning, emotional role limitations due to emotional problems, and mental health. Scores range from 0 to 100 for each dimension, with higher scores indicating better health status.	At the weeks 4, 8, and 12
Multidimensional Fatigue Inventory (MFI)	Fatigue is evaluated using the MFI, a 20-item assessment tool with five domains. Higher scores indicate a higher degree of fatigue.	At the weeks 4, 8, and 12
Medical Outcomes Study Sleep Scale (MOS)	The MOS is a questionnaire comprising 12 items that assess various aspects of sleep using a 6-point ordinal scale (1 indicating permanence and 6 indicating absence).	At the weeks 4, 8, and 12
Plasma concentrations of esketamine and its metabolites at the end of infusion		At the end of esketamine infusion, that is at day 0
Adverse events		Through study completion, an average of 12 weeks
The median pain relief time	The median pain relief time, defined as the time of 50% decrease in NRS score from baseline. Pain intensity will be measured using the NRS, where 0 indicates no pain, and 10 represents the worst imaginable pain.	Through study completion, an average of 12 weeks

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Beijing Ditan Hospital; Beijing Sanbo Brain Hospital

Publications and helpful links

Helpful Links

• Mathieson S, Lin C-WC, Underwood M, Eldabe S. Pregabalin and gabapentin for pain. BMJ. 2020;369:m1315. doi: 10.1136/bmj.m1315
• Gilron I, Chaparro LE, Tu D, Holden RR, Milev R, Towheed T, et al. Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial. Pain. 2016;157(7):1532-40. doi: 10.1097/j.pain.0000000000000558.
• VanderWeide LA, Smith SM, Trinkley KE. A systematic review of the efficacy of venlafaxine for the treatment of fibromyalgia. J Clin Pharm Ther. 2015;40(1):1-6. doi: 10.1111/jcpt.12216.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 3, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Fibromyalgia; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin; Esketamine
• Other Study ID Numbers: KY2025-217-03-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures and appendices) are available. Derived data supporting the findings of this study are available from the corresponding author Fang Luo on request.

Drug and device information, study documents

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