Efficacy and Safety of Pregabalin/Tizanidine vs. Pregabalin in Patients With Fibromyalgia

Efficacy and Safety of Pregabalin/Tizanidine vs. Pregabalin in Patients With Fibromyalgia: a Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) Trial

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, fatigue, and emotional disorders. Its onset is related to factors such as central sensitization and imbalance of neurotransmitters. The current mainstream treatments include pregabalin, but the efficacy of pregabalin is limited, with only 25%-40% pain relief rate, and adverse reactions are common.Tizanidine is an imidazoline derivative and a centrally acting alpha-2 receptor agonist with skeletal muscle relaxant, sedative and anxiolytic properties.we carried out an open-label clinical trial in order to evaluate the efficacy and safety of combined treatment with tizanidine and pregabalin for pain in FM.

Inclusion Criteria:

• 1.Aged 18-65 years. 2.Fulfill the 2016 updated American College of Rheumatology (ACR) diagnostic criteria for fibromyalgia.

  3.Sufficient cognitive function, visual acuity and language skills to complete questionnaires and pain diaries and to participate in telephone communication with study nurses to permit titration of the study drugs.

  4.Experienced daily pain (≥4/10 on a numerical rating scale) for at least 3 months.

Exclusion Criteria:

• 1.Presence of a painful condition, including inflammatory rheumatic disease, more than 50% as severe as but distinct from fibromyalgia.

  2.Women who are pregnant or lactating. 3.Women of childbearing potential not using adequate contraceptives. 4.End-stage kidney or liver disease. 5.Unstable cardiovascular disease (myocardial infarction within the preceding year, unstable angina, or congestive heart failure) or clinically relevant abnormal 12-lead electrocardiogram.

  6.Any poorly controlled medical condition that, in the opinion of the investigator, would interfere with proper conduct of the trial.

  7.Severe depression, as determined by a Beck Depression Inventory-II score of 29 or more suicidal ideation, as determined by a Beck Depression Inventory-II item 9 score of 2 or more any current major psychiatric disorder (e.g., schizophrenia, bipolar disorder) that is not well controlled.

  8.Hypersensitivity to any of the study medications. 9.Any current alcohol or drug abuse or dependence (except nicotine and caffeine).

  10.Those taking more than 90 mg morphine equivalents per day.