Is gabapentin (Neurontin) 600 mg three times a day (TID) effective for treating anxiety?

Gabapentin 600 mg TID for Anxiety: Not Recommended as First-Line

Gabapentin 600 mg three times daily (1800 mg/day total) should not be used as first-line treatment for anxiety disorders, as SSRIs (sertraline or escitalopram) are the evidence-based standard with superior efficacy and safety data. 1, 2

First-Line Treatment: SSRIs

• SSRIs are the established first-line pharmacological treatment for anxiety disorders based on strong efficacy evidence, favorable tolerability profiles, and minimal drug interactions 1, 2
• Sertraline should be started at 25 mg daily, increased to 50 mg after 3-7 days if tolerated, with a target range of 50-200 mg daily 2
• Escitalopram should be started at 5-10 mg daily, increased to 10 mg after one week, with a maximum of 20 mg daily 2
• SSRI response follows a logarithmic pattern: statistically significant improvement within 2 weeks, clinically significant improvement by week 6, and maximal improvement by week 12 or later 1

Gabapentin's Limited Role in Anxiety

Evidence Quality Issues

• No randomized controlled trials exist for gabapentin in generalized anxiety disorder (GAD), with only case reports and limited studies available 3, 4
• A systematic review concluded there are no studies for generalized anxiety disorder specifically, though gabapentin may have benefit for some anxiety disorders 4
• One placebo-controlled trial in panic disorder showed no overall drug/placebo difference (p = 0.606), with benefit only in post-hoc analysis of severely ill patients (PAS score ≥20) 5

When Gabapentin May Be Considered

Gabapentin could be used as an alternative option in these specific scenarios:

• Patients with comorbid neuropathic pain where gabapentin is already indicated at 100-1200 mg TID 2
• Patients who refuse or cannot tolerate SSRIs/SNRIs after adequate trials 2
• Breast cancer survivors with both anxiety and hot flashes, where gabapentin 300-900 mg showed anxiolytic effects at 4 and 8 weeks 6
• Patients with substance use history who cannot take benzodiazepines 6

Critical Dosing Concerns for Your Question

The 600 mg TID Dose Lacks Validation

• If gabapentin is used for anxiety, start with 100-300 mg daily and titrate slowly, not the 600 mg TID (1800 mg/day) you're asking about 2
• The 600 mg TID dosing falls within the neuropathic pain range (which can go up to 3600 mg/day in divided doses) but lacks specific validation for anxiety disorders 1, 2
• In the breast cancer anxiety study, 300 mg daily was associated with better outcomes than 900 mg daily for most patients except those with highest baseline anxiety 6
• Gabapentin has nonlinear pharmacokinetics due to saturable absorption, requiring careful titration from low doses 1

Side Effects at Higher Doses

• Common adverse effects include dose-dependent dizziness and sedation, which are reduced by starting with lower dosages 1
• Additional side effects include somnolence, headache, and potential lower extremity edema 1, 5
• Dosage reduction is required in patients with renal insufficiency 1

Practical Algorithm

Step 1: Initiate SSRI (sertraline 25-50 mg or escitalopram 5-10 mg daily) as first-line 1, 2

Step 2: If SSRI fails after adequate 12-week trial or is not tolerated, consider alternative SSRI or SNRI (venlafaxine 37.5 mg, titrate to 150-225 mg/day) 1, 2

Step 3: Only after SSRI/SNRI failure or contraindication, consider gabapentin starting at 100-300 mg daily (not 600 mg TID), titrating slowly over weeks based on response and tolerability 2

Step 4: If comorbid neuropathic pain exists, gabapentin becomes more appropriate at standard neuropathic pain dosing (starting 100-300 mg at bedtime or TID, increasing by 100-300 mg every 1-7 days as tolerated) 1