The Efficacy and Safety of Pregabalin Combined with Venlafaxine in Fibromyalgia Patients: Protocol for a Prospective, Randomized, Open-Label, Blinded-Endpoint Trial.

BACKGROUND

Fibromyalgia (FM) is a chronic condition characterized by widespread pain and a range of somatic and psychological symptoms that impose a substantial burden on patients. While pregabalin is an approved and effective monotherapy for many individuals with FM, the efficacy of this medication is often incomplete, particularly for symptoms like fatigue and anxiety. Combination therapy incorporating selective serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine, has shown promise for enhancing therapeutic outcomes. Venlafaxine, an SNRI with demonstrated efficacy as an FM treatment, has a distinct pharmacological mechanism from pregabalin. However, the synergistic potential of pregabalin and venlafaxine in combination has not been formally evaluated.

OBJECTIVES

This study protocol describes a trial designed to test the hypothesis that the combination of pregabalin and venlafaxine is superior to pregabalin monotherapy in providing pain relief to patients with FM.

STUDY

DESIGN

This is a multicenter, prospective, randomized, open-label, blinded-endpoint study.

SETTING

This study will be conducted at 7 different hospitals.

METHODS

We will recruit 750 adults with a diagnosis of FM and moderate-to-severe pain. Patients will be randomly assigned in a one-to-one ratio to receive either pregabalin monotherapy or combination therapy consisting of pregabalin and venlafaxine for 12 weeks. Both groups will follow a flexible, forced-titration schedule to achieve the maximum tolerated dose. While the patients and treating physicians will be aware of the treatment allocation, the outcome assessors will remain blinded.

RESULTS

The primary outcome is the mean daily pain intensity at week 4, measured on an 11-point numeric rating scale. Secondary outcomes will be evaluated at baseline and at weeks one, 2, 4, 8, and 12 after the treatment initiation. Secondary outcomes include the worst pain intensity, the responder rates (≥ 30% and ≥ 50% pain reduction), the dose of pregabalin and/or venlafaxine, the Revised FM Impact Questionnaire, the Brief Pain Inventory severity and interference subscales, the 36-Item Short Form Survey (SF-36), the Medical Outcomes Study Sleep Scale, the Beck Depression Inventory-II, and adverse events (AEs) occuring throughout the study. Statistical analyses will be performed on the modified intention-to-treat population.

LIMITATIONS: An open-label design will be employed, with patient follow-up limited to 12 weeks.

CONCLUSION

If the combination of pregabalin and venlafaxine proves to be more effective and better tolerated than pregabalin monotherapy, the combination therapy could establish a new standard of care for FM patients who struggle to achieve sufficient pain relief through nonpharmacological therapies.