What is the recommended dose of pregabalin (Lyrica) for treating fibromyalgia?

Pregabalin Dosing for Fibromyalgia

For fibromyalgia, start pregabalin at 75 mg twice daily (150 mg/day total) and increase to a target dose of 300-450 mg/day divided twice daily within one week based on tolerability. 1

FDA-Approved Dosing Regimen

The FDA label provides the following specific titration schedule 1:

• Starting dose: 75 mg twice daily (150 mg/day total)
• Week 1 increase: May increase to 150 mg twice daily (300 mg/day) based on efficacy and tolerability
• Further titration: Patients not experiencing sufficient benefit with 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 because trials studying 600 mg/day showed no additional benefit and significantly worse tolerability. 1

Evidence Supporting This Dosing

The 2017 EULAR guidelines reviewed high-quality systematic reviews showing pregabalin at fixed doses of 300,450, and 600 mg/day demonstrated efficacy, though the 600 mg dose offered no additional benefit over lower doses. 2 The number needed to treat (NNT) for pregabalin in fibromyalgia was 4.93, indicating moderate efficacy. 2

Multiple randomized controlled trials confirm that 450 mg/day provides optimal balance between efficacy and tolerability 3, 4:

• At 450 mg/day: 29% of patients achieved ≥50% pain reduction versus 13% with placebo
• Significant improvements in sleep quality, fatigue, and quality of life occurred at 300-450 mg/day doses
• The 600 mg dose showed higher discontinuation rates due to adverse effects without additional pain relief

Practical Titration Strategy

Start lower than FDA recommendations in clinical practice to minimize side effects 5:

• Initial dose: 25-50 mg at bedtime (not the FDA starting dose)
• Gradual uptitration: Increase weekly by 25-75 mg increments based on tolerability
• Target therapeutic range: 300-450 mg/day divided twice daily
• Time to assess efficacy: Allow 2-4 weeks at target dose before determining treatment response 1

This slower titration reduces the most common adverse effects—somnolence, dizziness, and cognitive dysfunction—which are dose-dependent. 5

Dose Adjustments for Renal Impairment

Reduce doses in patients with creatinine clearance <60 mL/min because pregabalin is eliminated primarily by renal excretion. 1 For example, a patient with CrCl of 30-60 mL/min starting fibromyalgia treatment should receive 75 mg/day (not 150 mg/day), administered in 2-3 divided doses. 1

Common Pitfalls to Avoid

• Avoid starting at high doses: Beginning at 150 mg twice daily causes excessive sedation and dizziness, leading to early discontinuation. Start at 25-50 mg nightly instead. 5
• Don't exceed 450 mg/day for fibromyalgia: The 600 mg dose has no additional efficacy but significantly more adverse effects including weight gain and peripheral edema. 1, 3
• Don't assess efficacy too early: Allow adequate time (2-4 weeks) at the target dose before concluding treatment failure. 1
• Don't abruptly discontinue: Taper gradually over at least one week to avoid withdrawal symptoms. 5

Monitoring and Safety

Watch for dose-related adverse effects 2, 5:

• Most common: Dizziness, somnolence, peripheral edema, weight gain
• Number needed to harm (NNH): 12 for withdrawal due to adverse events at therapeutic doses 2
• Drug interactions: Pregabalin worsens sedation when combined with CNS depressants 5
• Psychiatric monitoring: Assess for emergence or worsening of depression and suicidal ideation 5

The increased likelihood of withdrawal due to adverse events (RR 1.68,95% CI 1.36-2.07) emphasizes the importance of slow titration and patient education about expected side effects. 2