Can gabapentin (GABA analog) be used to treat anxiety?

Gabapentin for Anxiety Treatment

Gabapentin can be considered as a second-line treatment for anxiety disorders, particularly social anxiety disorder, when first-line SSRIs/SNRIs have failed or are contraindicated, though evidence remains limited and concerns about dependence and long-term safety warrant caution. 1

Treatment Hierarchy

First-Line Options (Use These First)

• SSRIs and SNRIs remain the recommended first-line pharmacological treatments for anxiety disorders with substantial evidence supporting their efficacy 1
• Cognitive behavioral therapy (CBT) should be offered as first-line non-pharmacological treatment 1
• Benzodiazepines may be used only for short-term management of severe anxiety due to dependence risks 1

When to Consider Gabapentin

Consider gabapentin only after first-line treatments have failed or are contraindicated 1. The Canadian Clinical Practice Guideline specifically lists gabapentin as a second-line drug for social anxiety disorder 1.

Evidence Quality and Limitations

Supporting Evidence

• In more severely ill panic disorder patients (Panic and Agoraphobia Scale score ≥20), gabapentin showed significant improvement compared to placebo (p=0.04), though no overall benefit was seen in the general panic disorder population 2
• Gabapentin 1,200 mg reduced preoperative anxiety scores (effect size 1.44) and pain catastrophizing in highly anxious patients 3
• A systematic review found gabapentin may have benefit for some anxiety disorders, though no studies exist for generalized anxiety disorder specifically 4

Critical Safety Concerns

• Gabapentin carries risks of tolerance, dependence, addiction, and withdrawal similar to benzodiazepines 5
• Deaths involving pregabalin (a related gabapentinoid) now exceed those from diazepam, with 244 deaths recorded in 2019, usually involving concomitant opioid use 5
• Evidence for anxiety treatment derives only from short-term trials with marginal differences from placebo, not accounting for long-term tolerance and dependence 5
• Common side effects include somnolence (80% in some studies), dizziness, and sedation 6, 3

Specific Clinical Scenarios Where Gabapentin May Be Preferred

Prioritize gabapentin over other second-line options when patients have comorbid conditions that benefit from its use: 1

• Neuropathic pain (gabapentin is first-line for HIV-associated neuropathic pain at 2,400 mg/day) 6
• Seizure disorders 1
• Insomnia 1
• Alcohol use disorder (gabapentin has clearer efficacy for alcohol craving and withdrawal) 4

Dosing Considerations

• Studies in anxiety have used flexible dosing between 600-3,600 mg/day 2
• For preoperative anxiety, 1,200 mg as a single dose was effective 3
• Titration is typically needed to minimize side effects, particularly somnolence and dizziness 6

Common Pitfalls to Avoid

• Do not use gabapentin as first-line treatment when SSRIs/SNRIs are appropriate 1
• Avoid long-term prescribing without regular reassessment given dependence risks and lack of long-term efficacy data 5
• Do not combine with opioids due to increased overdose death risk 5
• Monitor for sedation which may delay discharge in ambulatory settings 3
• No evidence supports use in generalized anxiety disorder, PTSD, or OCD 4

Monitoring Requirements

• Evaluate treatment response regularly using standardized anxiety measures 1
• Assess for signs of tolerance, dependence, or misuse given controlled substance classification 5
• Monitor sedation levels, particularly in the first week when side effects are most prominent 6