Pregabalin (Lyrica) Dosing for Generalized Anxiety Disorder
For GAD, start pregabalin at 150 mg/day divided into two or three doses, then increase to 300 mg/day within the first week, with a maximum dose of 600 mg/day for patients requiring additional symptom control. 1, 2
Initial Dosing Strategy
- Begin with 150 mg/day, administered as either 75 mg twice daily or 50 mg three times daily 3, 2
- This starting dose has demonstrated efficacy superior to placebo in controlled trials of patients with moderate-to-severe GAD 2, 4
- Pregabalin shows rapid onset of anxiolytic activity, with significant improvement evident within 1 week of treatment initiation 2, 4
Dose Escalation
- Increase to 300 mg/day (150 mg twice daily or 100 mg three times daily) within the first week based on efficacy and tolerability 3, 4
- The 300 mg/day dose is considered the standard therapeutic dose for GAD and is effective for both psychological and somatic anxiety symptoms 1
- For patients with inadequate response after 2-4 weeks on 300 mg/day who tolerate the medication well, increase to 600 mg/day (300 mg twice daily or 200 mg three times daily) 3, 1
Maximum Dosing
- The maximum recommended dose is 600 mg/day, divided into two or three doses 3, 5
- Doses of 450-600 mg/day have demonstrated efficacy in relapse prevention over 34 weeks 4
- Higher doses beyond 300 mg/day often increase side effects without proportional additional benefit, though individual response varies 3
Special Population Adjustments
Elderly Patients
- Start with lower doses (50 mg twice daily) and implement slower titration 3
- Elderly patients have increased risk of dizziness, somnolence, confusion, and falls 3
Renal Impairment
- Mandatory dose reduction required as pregabalin is eliminated primarily by renal excretion 3
- Reduce total daily dose by approximately 50% for creatinine clearance 30-60 mL/min 3
- Reduce by 75% for creatinine clearance 15-30 mL/min 3
- Reduce by 85-90% for creatinine clearance <15 mL/min 3
Common Side Effects and Management
- Primary adverse effects include dizziness (23-46%), somnolence (15-25%), and peripheral edema (10%) 3, 5
- These effects are dose-dependent and typically mild to moderate in severity 4
- Side effects can be minimized by starting with lower doses and gradual titration 3, 5
- Across clinical trials, adverse events led to study withdrawal in up to 32% of patients 5
Treatment Duration and Discontinuation
- Allow 4 weeks at therapeutic dose to assess adequate treatment response 3
- Pregabalin demonstrates sustained efficacy with 450 mg/day effective for relapse prevention over 34 weeks 1, 4
- When discontinuing, taper gradually over a minimum of 1 week to avoid withdrawal symptoms 3
- Unlike benzodiazepines, pregabalin does not appear to cause clinically significant withdrawal syndrome with appropriate tapering 2, 4
Clinical Advantages
- Pregabalin has linear pharmacokinetics, making dosing more predictable than gabapentin 3
- Onset of anxiolytic effect occurs within 1 week, faster than SSRIs like venlafaxine 4
- Effective for both psychological and somatic anxiety symptom clusters 1
- Also reduces depressive symptoms commonly associated with GAD, particularly at 300-450 mg/day 6
- No serious adverse events were reported in controlled GAD trials 2