What is the role of pregabalin (an anticonvulsant) in treating physical anxiety in adult patients with impaired renal function or a history of substance abuse?

Pregabalin for Physical Anxiety

Pregabalin is not a first-line treatment for anxiety disorders and should be avoided in patients with substance abuse history due to dependence risk, while requiring dose adjustment in renal impairment. 1, 2

Evidence-Based Recommendations

Primary Treatment Approach

• SSRIs and SNRIs are the recommended first-line pharmacotherapy for anxiety disorders, not pregabalin. 1
• The Japanese Society of Anxiety and Related Disorders/Japanese Society of Neuropsychopharmacology guidelines specifically recommend SSRIs (fluvoxamine, paroxetine, sertraline, escitalopram) and SNRIs (venlafaxine, duloxetine) as first-line treatments with strong evidence. 1
• Pregabalin and other anticonvulsants are not included in guideline recommendations for social anxiety disorder due to inadequate study. 1

Pregabalin's Limited Role in Anxiety

While pregabalin has demonstrated efficacy in generalized anxiety disorder (GAD) in research trials, it faces significant limitations:

• Efficacy: Pregabalin 150-600 mg/day showed superiority to placebo and comparable efficacy to benzodiazepines (alprazolam, lorazepam) and venlafaxine in GAD trials, with onset of action within 1 week. 3, 4, 5
• Both psychic and somatic anxiety symptoms improved with pregabalin treatment in clinical trials. 6, 4
• In elderly patients (≥65 years), pregabalin 150-600 mg/day demonstrated efficacy with early onset by week 2. 6

Critical Safety Concerns

Substance Abuse Risk:

• Pregabalin carries risk of abuse and dependence, particularly concerning in patients with substance abuse history. 1, 7
• The CDC guideline notes that pregabalin is associated with adverse effects including blurred vision, cognitive effects, sedation, weight gain, dizziness, and peripheral edema. 1
• Approximately 50% of patients dispensed pregabalin in England had been treated continuously for at least 12 months, raising concerns about long-term dependence. 1
• Discontinuation can lead to physical and psychological withdrawal symptoms, requiring careful tapering over minimum 1 week. 1, 2

Renal Impairment Considerations:

• Pregabalin is eliminated primarily by renal excretion and requires dose adjustment in renal impairment. 2
• For creatinine clearance 30-60 mL/min: reduce total daily dose by 50%. 2
• For creatinine clearance 15-30 mL/min: reduce total daily dose by 75%. 2
• For hemodialysis patients: adjust daily dose based on renal function plus supplemental dose after each 4-hour dialysis session. 2
• Slower titration is required for elderly or medically frail patients. 1

Appropriate Clinical Context

Pregabalin may be considered in specific scenarios:

• Neuropathic pain with comorbid anxiety where it addresses both conditions simultaneously. 1
• Patients who have failed or cannot tolerate SSRIs/SNRIs. 4, 5
• When rapid onset of anxiolytic effect is needed (within 1 week vs. 2-4 weeks for SSRIs). 4
• Never as first-line therapy in patients with substance abuse history. 1, 7

Dosing for Anxiety (When Used)

• Starting dose: 150 mg/day (50 mg three times daily or 75 mg twice daily). 2
• Target dose: 300-450 mg/day in divided doses. 2
• Maximum dose: 600 mg/day, though no additional benefit demonstrated above 450 mg/day with increased adverse effects. 2
• Titrate gradually based on tolerability, typically increasing weekly. 2

Common Pitfalls to Avoid

• Do not use pregabalin as first-line treatment when SSRIs/SNRIs are appropriate and available. 1
• Do not prescribe without screening for substance abuse history - this is a critical contraindication. 1, 7
• Do not use standard dosing in renal impairment - always calculate creatinine clearance and adjust accordingly. 2
• Do not abruptly discontinue - taper over minimum 1 week to avoid withdrawal symptoms. 2
• Do not combine with opioids without extreme caution - dangerous respiratory depression can occur. 1
• Most common adverse effects (dizziness, somnolence) are dose-dependent and typically mild-to-moderate, self-limiting within 4-16 days. 3, 6