What is the recommended dosing for pregabalin (an anticonvulsant) in the treatment of anxiety?

Pregabalin Dosing for Anxiety

For generalized anxiety disorder, start pregabalin at 150 mg/day divided into two or three doses, then titrate to an effective dose of 300-450 mg/day, with a maximum of 600 mg/day if needed.

Starting Dose

• Begin with 150 mg/day (either 50 mg three times daily or 75 mg twice daily) 1, 2
• This initial dose may be insufficient for full therapeutic effect but establishes tolerability 3

Titration Strategy

• Increase to 300 mg/day within the first week if tolerated, as this represents the minimum clinically effective dose range 3
• The optimal therapeutic range is 300-450 mg/day, where effect sizes consistently exceed clinically meaningful thresholds 3
• Further increases to 600 mg/day can be considered but typically do not provide additional benefit beyond 450 mg/day 3
• Dose escalation should occur gradually over several days to minimize adverse effects 1

Dosing Schedule

• Administer in divided doses: either twice daily or three times daily 4, 1
• The three-times-daily regimen (e.g., 100 mg TID for 300 mg total) may provide more consistent coverage given pregabalin's 6.3-hour half-life 1
• Both regimens have demonstrated equivalent efficacy in clinical trials 1

Special Populations

Elderly Patients (≥65 years)

• Use the same starting dose of 150 mg/day with flexible titration up to 600 mg/day 5
• Elderly patients respond well to standard dosing, with significant improvement observed by week 2 5
• Slower titration may be warranted in frail elderly or those with renal impairment 6

Renal Impairment

• Dose adjustment is required for patients with reduced kidney function, as pregabalin is excreted largely unchanged 4, 1
• Reduce doses proportionally based on creatinine clearance 4

Timeline for Response

• Anxiolytic effects begin within 1 week of starting treatment, similar to benzodiazepines and faster than SSRIs/SNRIs 1, 5
• Significant improvement is typically evident by week 2 5
• Full therapeutic effect develops over 4-8 weeks 1

Efficacy Considerations

• Pregabalin demonstrates consistent efficacy across both psychic and somatic anxiety symptoms, which may be superior to some comparators 1
• The medication is effective in patients with moderate to severe baseline anxiety and those with comorbid subsyndromic depression 1
• Effect sizes plateau in the 200-450 mg/day range, with minimal additional benefit at 600 mg/day 3

Common Pitfalls to Avoid

• Do not stop at 150 mg/day: This dose is below the therapeutic threshold for most patients and may lead to perceived treatment failure 3
• Avoid rapid discontinuation: Taper over at least one week to minimize withdrawal symptoms (headache, nausea, dizziness), even though pregabalin has lower withdrawal risk than benzodiazepines 1, 2
• Do not use a one-size-fits-all approach: While 300-450 mg/day is optimal for most patients, individual response varies 6

Tolerability Profile

• Most common adverse effects are dizziness and somnolence, which are dose-related and typically mild-to-moderate 5, 2
• Tolerance to sedation develops within a few weeks of continued treatment 1
• Adverse events are generally self-limiting with median duration of 4-16 days 5
• Pregabalin shows less cognitive and psychomotor impairment than benzodiazepines 1