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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
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.
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.
Beijing Tiantan Hospital, Beijing, Beijing 100070
Beijing, China
RECRUITINGChange 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.
Time frame: At the week 1.
Average pain intensity
The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable.
Time frame: 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.
Time frame: 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.
Time frame: at weeks 1, 2, 4, 8, and 12
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.
Time frame: Through study completion, an average of 12 weeks
The maximal tolerated doses of pregabalin and venlafaxine
Time frame: at weeks 1, 2, 4, 8, and 12
The Revised FM Impact Questionnaire (FIQR)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: At the weeks 4, 8, and 12
Plasma concentrations of esketamine and its metabolites at the end of infusion
Time frame: At the end of esketamine infusion, that is at day 0
Adverse events
Time frame: Through study completion, an average of 12 weeks