What is the recommended dosing for Lyrica (pregabalin) in the treatment of fibromyalgia (FM) and myofascial pain?

Lyrica (Pregabalin) Dosing for Fibromyalgia and Myofascial Pain

For fibromyalgia, start pregabalin at 75 mg twice daily (150 mg/day) and titrate to 150 mg twice daily (300 mg/day) within one week, with a maximum effective dose of 225 mg twice daily (450 mg/day) for those requiring additional benefit. 1

FDA-Approved Dosing for Fibromyalgia

The FDA label provides the definitive dosing algorithm 1:

• Initial dose: 75 mg twice daily (150 mg/day)
• Week 1 titration: Increase to 150 mg twice daily (300 mg/day) based on efficacy and tolerability
• Further titration if needed: Patients not experiencing sufficient benefit at 300 mg/day may increase to 225 mg twice daily (450 mg/day)
• Maximum recommended dose: 450 mg/day
• Doses above 450 mg/day are NOT recommended - the 600 mg/day dose showed no additional benefit but significantly more adverse effects 1

Practical Initiation Strategy to Minimize Side Effects

While the FDA label states 75 mg twice daily as the starting dose, clinical experience suggests initiating at 25-50 mg at bedtime to minimize somnolence, dizziness, and cognitive dysfunction, then uptitrating weekly based on tolerability 2. This lower starting approach is not FDA-approved but reflects real-world practice to improve adherence.

Evidence Supporting Dosing Recommendations

The 450 mg/day dose demonstrates the strongest efficacy profile 3, 4:

• Substantial benefit (≥50% pain reduction): 24% with pregabalin 450 mg vs 14% with placebo (NNT = 11) 4
• Moderate benefit (≥30% pain reduction): 39-43% with pregabalin 300-600 mg vs 28% with placebo (NNT = 7-14) 4
• The 450 mg dose reduced pain by 0.93 points on a 0-10 scale compared to placebo 3

The 300 mg/day dose provides meaningful benefit with better tolerability 5, 4:

• Meta-analysis shows 300 mg/day is effective (NNT: 12) with fewer adverse events than higher doses 5
• Both 300 mg and 450 mg doses improved sleep quality, fatigue, and quality of life 3

Myofascial Pain Considerations

Pregabalin is NOT FDA-approved for myofascial pain specifically 1. The evidence base and dosing recommendations are exclusively for fibromyalgia. EULAR guidelines recommend pregabalin for fibromyalgia pain reduction (Level Ib evidence, Grade A recommendation) but do not address myofascial pain as a separate indication 6.

Dose-Related Adverse Effects

Common adverse events are dose-dependent and occur in 70-90% of patients 4:

• Dizziness: NNH = 3.7 (most common, highly dose-related)
• Somnolence: NNH = 7.4
• Weight gain: NNH = 18
• Peripheral edema: NNH = 19
• Withdrawal rate due to adverse events: 10% higher than placebo 4

These adverse effects explain why the 600 mg dose is not recommended despite being studied - no additional efficacy but worse tolerability 1, 3.

Dosing Algorithm Summary

1. Start: 25-50 mg at bedtime (clinical practice) or 75 mg twice daily (FDA label) 1, 2
2. Week 1: Increase to 150 mg/day (75 mg twice daily) if starting low, or 300 mg/day (150 mg twice daily) if following FDA label 1
3. Week 2-4: Assess response at 300 mg/day for 2-4 weeks 1
4. If inadequate response: Increase to 450 mg/day (225 mg twice daily) 1
5. Maximum dose: 450 mg/day - do not exceed 1

Critical Prescribing Caveats

• Renal adjustment required: Pregabalin is renally eliminated; reduce dose based on creatinine clearance 1
• Gradual discontinuation necessary: Taper slowly to avoid withdrawal symptoms 2
• Monitor for depression/suicidality: Required monitoring per FDA label 2
• CNS depressant interactions: Worsens sedation when combined with other CNS depressants 2
• No hepatic metabolism: Safe in liver disease and minimal drug interactions due to lack of protein binding 2