All patients receive tizanidine in an open-label fashion. The tizanidine dose is slowly escalated over approximately 3 weeks. The initial dosage is 2 mg/d at bedtime. The dosage is increased by 2 mg every 2 days in the first week in 3 divided doses. The dosage is then increased more rapidly by 4 mg every 2 days in the second week divided 3 times a day. During the third week, the dose was further escalated by 6 mg every 2 days to a maximum of 24 mg/d divided 3 times a day. If a patient could not tolerate a particular current specific dosage increase because of side effects, he or she is maintain at the previous dosage during the trial period. The patients receive open-label pregabalin (Pfizer Pharmaceutical Co. Ltd, New York) titration therapy. In the first week, patients receive the starting dose of 150 mg/day (75 mg twice daily) escalated, based on efficacy and tolerability, at weekly visits to increase by 150 mg per week. A final dose of 450 mg/day (225 mg twice daily).

Health Related Quality of Life assessments are made using the Medical Outcome Study Short Form 36 Health Survey (SF-36). The SF-36 is a self-administered, 36-item questionnaire that assesses the concepts of physical functioning, role limitations due to physical problems, social function, bodily pain, general mental health, role limitations due to emotional problems, vitality, and general health perceptions. Summary scores include physical function, mental function, and combined total function. Scores range from 0 to 100, with higher scores indicating better health status.

The Patient's Global Assessment (Global Visual Analogue Scale) is a visual analogue scale that measures the level of fibromyalgia severity on a 10-point scale with 10 reflecting the most extreme severity and 0 reflecting no severity.

The Beck II Depression Inventory (BDI) is a 21-question, validated, self-report instrument that measures the severity of depressive symptoms (each scored 0-3, sum=0-63). Higher scores reflect a greater degree of symptom severity. The total questionnaire score ranges from 0 to 63 points. The result is interpreted by the usual classifications as follows: no depression (0-9 points), mild depression (10-18 points), moderate depression (19-29 points) and severe depression (>30 points).

The Pittsburgh Sleep Quality Index is an 11-item, validated, self-report questionnaire that measures sleep quality. Lower scores are associated with better sleep quality. This questionnaire has 7 dimensions: subjective quality, sleep latency, sleep duration, habitual sleep efficacy, sleep perturbations, use of hypnotic medication, and daily dysfunction. Each dimension is scored from 0 (no problems) to 3 (severe problems), where the total score varies in a range from 0 to 21 points.

The Hospital Anxiety and Depression Scale is a 14-item, validated, self-report questionnaire that assesses levels of depression and anxiety. Higher scores reflect greater levels of anxiety and depression.

The Perceived Stress Scale is the most widely used psychological instrument for measuring the perception of stress. The 10-item scale also includes a number of direct queries about current levels of experienced stress. For this instrument, higher scores reflect a greater degree of symptom severity.

Pain distribution: assessed by the Widespread Pain Index (WPI) from the 2016 diagnostic criteria for fibromyalgia.

Frequency and severity of AEs, Patient safety will be ensured by vigilant AE assessment and judicious drug titration. Any occurrences of major AEs will be tracked as secondary outcomes and also reported to the Ethics Board. Assessment and reporting of AEs will adhere to Consolidated Standards for Reporting Trials recommendations.