Lyrica (Pregabalin) Dosing for Anxiety
Pregabalin is not FDA-approved for anxiety disorders in the United States, though it has demonstrated efficacy in clinical trials for generalized anxiety disorder at doses of 150-600 mg/day divided into 2-3 daily doses. 1, 2
Starting Dose and Titration
- Begin with 150 mg/day divided into either twice-daily or three-times-daily dosing 3, 4
- The initial dose of 150 mg/day has shown efficacy as early as week 1 in clinical trials 4
- Titrate to 300 mg/day after 3-7 days if needed, then increase by 150 mg/day every 3-7 days as tolerated 5
Target and Maximum Doses
- Effective dose range: 150-600 mg/day 1, 2, 4
- Maximum dose: 600 mg/day (200 mg three times daily or 300 mg twice daily) 5
- Doses of 150 mg/day, 600 mg/day, and intermediate doses all showed significantly greater anxiety reduction compared to placebo 4, 6
- Higher doses (>300 mg/day) are not consistently more effective than 300 mg/day but are associated with greater adverse effects 5
Special Populations
Elderly Patients (≥65 years)
- Use the same dose range (150-600 mg/day) but employ slower titration 3, 6
- Pregabalin was safe and effective in elderly patients with generalized anxiety disorder, with efficacy apparent by week 2 6
Renal Impairment
- Dose adjustment is mandatory for patients with reduced kidney function 3
- If eGFR <30 mL/min, reduce doses proportionally based on creatinine clearance 5, 3
- Pregabalin is excreted largely unchanged and requires dose reduction in renal insufficiency 5
Administration Schedule
- Administer in divided doses: either twice daily or three times daily 3, 2
- Both dosing schedules (BID and TID) have demonstrated efficacy 2
Duration of Trial
- Allow 4 weeks for an adequate therapeutic trial 5
- Anxiolytic effects may be apparent within 1 week, similar to benzodiazepines and faster than venlafaxine 2, 4
Common Pitfalls and Safety Considerations
- Most common adverse effects: dizziness (up to 49%) and somnolence (up to 50%) 1
- These side effects are typically mild-to-moderate, self-limiting (median duration 4-16 days), and tolerance develops within a few weeks 2, 6
- Abuse potential exists, particularly in patients prescribed antipsychotics and benzodiazepines 7
- Approximately 9.6% of users may exceed 600 mg/day for 6 months, with male gender and concurrent benzodiazepine use as risk factors 7
- No significant withdrawal syndrome when tapered over 1 week 2, 4
- Pregabalin shows less cognitive and psychomotor impairment than benzodiazepines 2
Clinical Context
While pregabalin demonstrated efficacy comparable to alprazolam and lorazepam in clinical trials, with more consistent effects on both psychic and somatic anxiety factors 2, it remains off-label for anxiety in the United States. The evidence supports its use when first-line treatments (SSRIs, SNRIs) have failed or are contraindicated, particularly given its favorable withdrawal profile compared to benzodiazepines 4.