Can pregabalin (an anticonvulsant) be used to treat anxiety?

Pregabalin for Anxiety: Efficacy, Safety, and Clinical Applications

Pregabalin is an effective treatment option for anxiety disorders, particularly generalized anxiety disorder (GAD), with evidence supporting its use as a first-line medication in certain clinical guidelines.

Efficacy and Mechanism of Action

Pregabalin works through a distinct mechanism compared to traditional anxiolytics:

• Binds to α2δ subunits of voltage-dependent calcium channels
• Inhibits excitatory neurotransmitter release
• Provides anxiolytic effects through modulation of neuronal excitability 1

Key advantages of pregabalin for anxiety treatment include:

• Rapid onset of action (typically ≤1 week), faster than SSRIs/SNRIs 1, 2
• Effective for both psychic (emotional) and somatic (physical) symptoms of anxiety 3
• Maintains long-term improvement and delays relapse 1

Clinical Guideline Recommendations

The Canadian Clinical Practice Guideline (Canadian CPG) lists pregabalin as a first-line treatment for social anxiety disorder, alongside SSRIs, SNRIs, and other medications 4. This recommendation is significant as it places pregabalin among established anxiety treatments.

In clinical trials, pregabalin has demonstrated:

• Consistent efficacy across the licensed dose range of 150-600 mg/day 3
• Superiority to placebo and comparable efficacy to established anxiolytics like lorazepam, alprazolam, and venlafaxine 5
• Efficacy in elderly patients with GAD 6

Dosing and Administration

For anxiety treatment:

• Starting dose: 150 mg/day (divided into 2-3 doses)
• Titration: Increase gradually based on response and tolerability
• Target dose: 300-600 mg/day for most patients
• Maximum dose: 600 mg/day 7

Safety Profile and Adverse Effects

Common adverse effects include:

• Dizziness (most common)
• Somnolence
• Dry mouth
• Weight gain
• Edema 7, 3

Most adverse effects are:

• Dose-related
• Mild to moderate in severity
• Transient (typically resolving within 4-16 days) 6

The discontinuation rate due to adverse effects in clinical trials was approximately 10.7%, similar to placebo (9.4%) 6.

Special Populations

Elderly Patients

Pregabalin has demonstrated efficacy and safety in elderly patients (≥65 years):

• Significant reduction in anxiety symptoms compared to placebo
• Well-tolerated with adverse events generally mild to moderate
• Early onset of action (by week 2) 6

Patients with Treatment-Resistant Anxiety

Pregabalin may be beneficial for patients who have failed to respond to SSRIs or SNRIs:

• Can be used as monotherapy or adjunctive therapy
• Particularly useful when rapid anxiolysis is needed 1

Advantages Over Other Anxiolytics

Compared to benzodiazepines:

• Lower potential for abuse and dependence
• No clinically significant withdrawal syndrome when tapered appropriately
• No development of tolerance to anxiolytic effects 1, 5

Compared to SSRIs/SNRIs:

• Faster onset of action
• Equal efficacy with potentially better tolerability
• Different side effect profile that may be preferable for some patients 2

Practical Considerations

When discontinuing pregabalin:

• Taper gradually over at least one week to minimize withdrawal symptoms 3
• Monitor for potential withdrawal symptoms, although risk is generally low

For optimal outcomes:

• Explain expected benefits and potential side effects to patients
• Start with lower doses and titrate up as needed
• Consider concomitant cognitive-behavioral therapy for enhanced outcomes 2

Conclusion

Pregabalin represents an important treatment option for anxiety disorders with a unique mechanism of action, rapid onset, and favorable safety profile. It is particularly valuable for patients who cannot tolerate or have not responded to traditional anxiolytics like SSRIs or SNRIs.