Is gabapentin 900 mg three times a day (TID) effective for treating anxiety?

Gabapentin 900 mg TID for Anxiety: Evidence-Based Assessment

Gabapentin 900 mg three times daily (2700 mg/day total) is not supported by high-quality evidence for treating primary anxiety disorders and should not be used as first-line therapy. While some evidence suggests potential benefit in specific anxiety contexts, SSRIs (sertraline or escitalopram) remain the evidence-based first-line pharmacological treatment 1.

Evidence Quality and Limitations

The evidence base for gabapentin in anxiety disorders is notably weak:

• No randomized controlled trials exist for generalized anxiety disorder (GAD) specifically, with only scattered case reports available 2, 3
• A systematic review concluded there is no clear evidence for gabapentin therapy in primary anxiety disorders, though it may have benefit for "some anxiety disorders" 2
• The one placebo-controlled panic disorder trial (n=103) showed no overall drug/placebo difference on primary outcomes (p=0.606), with benefit only emerging in post-hoc analysis of severely ill patients 4

Context-Specific Evidence

Gabapentin does show efficacy in specific clinical contexts rather than primary anxiety disorders:

Breast Cancer Survivors

• A well-designed RCT (n=420) demonstrated that 300 mg daily was more effective than 900 mg for anxiety symptoms in breast cancer survivors 5
• At 4 weeks, both doses showed significant improvement versus placebo (p=0.005), with effects persisting at 8 weeks (p<0.005) 5
• The lower 300 mg dose produced better outcomes except in patients with highest baseline anxiety 5

Preoperative Anxiety

• Meta-analysis shows gabapentin reduces preoperative anxiety (SMD -0.92,95% CI -1.32 to -0.52) compared to placebo 6

Guideline-Supported First-Line Treatments

SSRIs are the evidence-based first-line pharmacological treatment for anxiety disorders:

• Sertraline or escitalopram are recommended as preferred initial SSRI therapy due to strong efficacy evidence, favorable tolerability, and minimal drug interactions 1
• Sertraline: Start 25 mg daily, increase to 50 mg after 3-7 days if tolerated, target range 50-200 mg daily 1
• Escitalopram: Start 5-10 mg daily, increase to 10 mg after one week, maximum 20 mg daily 1
• Combination CBT plus SSRI is superior to either alone for moderate-severe anxiety 1

When Gabapentin Might Be Considered

Gabapentin could be considered as an alternative option in specific circumstances:

• Patients with comorbid neuropathic pain where gabapentin is already indicated (100-1200 mg TID for neuropathic pain) 7
• Patients with substance use history who cannot take benzodiazepines and have failed SSRI trials 5
• Breast cancer survivors with both anxiety and hot flashes (but use 300 mg daily, not 900 mg TID) 5
• Patients who refuse or cannot tolerate SSRIs/SNRIs after adequate trials 1

Critical Dosing Considerations

If gabapentin is used for anxiety despite limited evidence:

• Start low and titrate slowly: Begin 100-300 mg daily, not 900 mg TID 7
• Evidence suggests lower doses (300 mg/day) may be more effective than higher doses for anxiety 5
• The 900 mg TID dosing (2700 mg/day total) is within the neuropathic pain range but lacks specific validation for anxiety 7
• Common side effects include somnolence (reported by 80% in one study), dizziness, and headache 7, 4

Common Pitfalls to Avoid

• Do not use gabapentin as first-line therapy when SSRIs have superior evidence 1, 2
• Do not assume higher doses are better - the 300 mg dose outperformed 900 mg in the best available anxiety trial 5
• Do not overlook the need for psychotherapy - medication alone is less effective than combination treatment 1
• Do not start at 900 mg TID without titration, as this increases side effect burden 7

Clinical Bottom Line

The 900 mg TID regimen lacks evidence-based support for primary anxiety disorders. Clinicians should prioritize SSRIs (sertraline or escitalopram) combined with CBT as first-line treatment 1. Gabapentin may have a role in specific populations (cancer survivors, comorbid neuropathic pain, substance use history) but should be initiated at lower doses (300 mg daily) with careful titration based on response 5, 2.