The Efficacy and Safety of Pregabalin Combined With Venlafaxine in Patients With Fibromyalgia

• Pregabalin (Drug): In general, for the pregabalin monotherapy group (Pregabalin Capsules, Pfizer, New York, USA), treatment will be initiated at 150 mg/day, administered in two divided doses. After 7 days, the dose will be increased to 300 mg/day. Thereafter, based on individual response and tolerability, the dose may be further increased to a maximum of 450 mg/day.
• Pregabalin with venlafaxine (Drug): For the combination therapy group, participants will receive both pregabalin and venlafaxine (Venlafaxine Hydrochloride Sustained-Release Capsules, Pfizer, Co Kildare, Ireland). The dose titration for pregabalin will be identical to that of the monotherapy group. Concurrently, venlafaxine will be initiated at 75 mg/day. If well-tolerated, the dose may be increased in 75 mg/day increments at weekly intervals, guided by clinical response and side effects profile, to a maximum dose of 225 mg/day.

Primary outcomes

• The average pain intensity [At the 4-weeks]: The average pain intensity over the past 24 hours, rated each morning upon awakening and averaged over 7 days at the 4 weeks. This will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable.

Secondary outcomes

• The worst pain intensity [At the weeks 1, 2, 4, 8, and 12]: 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.
• The proportion of patients achieving pain reduction [At the weeks 1, 2, 4, 8, and 12]: 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.
• Dose of pregabalin and/or venlafaxine [At the weeks 1, 2, 4, 8, and 12]: At the aforementioned follow-up time points, the researchers will inquire about the current dosages of pregabalin and/or venlafaxine being administered to the participants. Any dose adjustments, interruptions, or discontinuations, along with the reasons will be documented in detail.
• The Revised FM Impact Questionnaire [At the weeks 1, 2, 4, 8, and 12]: The Revised FM Impact Questionnaire assesses the severity of FM symptoms and their impact on daily functioning. It evaluates three linked domains: function, overall impact, and symptoms, using a 0 to10 NRS. The total score ranges from 0 to 100, with higher scores indicating greater disease burden.
• The Brief Pain Inventory (BPI) severity (BPI-S) and interfere (BPI-I) subscales [At the weeks 1, 2, 4, 8, and 12]: BPI-S accesses pain intensity over the past 24 hours, calculated as the average of items 3 to 6 on the BPI, scored using a 0 to 10 NRS. In the NRS scale, 0 indicates no pain, while 10 represents the worst pain imaginable. The total score ranges from 0 to 40, with higher scores indicating greater pain severity. BPI-I evaluates the degree to which pain interferes with daily activities, including general activity, mood, mobility work, relationships, sleep, and pleasure. This subscale comprises 7 items, each scored from 0 (no interference) to 10 (complete interference), with a total score ranging from 0 to 70.
• The short-form 36 Health Survey (SF-36) [At the weeks 1, 2, 4, 8, and 12]: 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.
• The Medical Outcomes Study Sleep Scale (MOS) [At the weeks 1, 2, 4, 8, and 12]: 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).
• The Beck Depression Inventory-Ⅱ (BD-Ⅱ) [At the weeks 1, 2, 4, 8, and 12]: The BD-Ⅱ evaluates the severity of depressive symptoms using a 4-point scale from 0 to 3, where 0 indicates no symptom and 3 indicates severe symptomatology. It comprises 21 items, the total score ranging from 0 to 63.
• Adverse Events [Through study completion, an average of 12 weeks]: The incidence and proportion of adverse events will be recorded and categorized as mild, moderate, severe, or life-threatening. AEs are defined as events that arise during treatment, were absent before treatment, or worsen relative to the pretreatment state.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosed with FM according to the 2016 Revisions to the 2010/2011 FM diagnostic criteria;
* Aged more than 18 years;
* Suffering from moderate to severe FM with 11-point numeric rating scale (NRS) score more than 4 at baseline that have not been effectively alleviated by non-pharmacological treatments and has not received currently recommended pharmacological treatment for FM;
* Agreed to sign the informed consent form.

Exclusion criteria

* A history of psychiatric disease;
* Hypersensitivity or have contraindications to pregabalin, venlafaxine;
* Pregnancy or breastfeeding;
* Presence of serious systemic diseases, including uncontrolled hypertension, uncontrolled diabetes, significant cardiac dysfunction, or chronic hepatic or renal dysfunction;
* With acute or chronic pain conditions other than FM.