Can gabapentin be used as monotherapy for anxiety in adult patients?

Gabapentin as Monotherapy for Anxiety

Gabapentin should NOT be used as monotherapy for anxiety disorders in adults. SSRIs (escitalopram or sertraline) or SNRIs (venlafaxine or duloxetine) are the evidence-based first-line pharmacological treatments, with gabapentin/pregabalin reserved only as second-line options when first-line treatments fail or are not tolerated 1.

Evidence-Based First-Line Treatment

The guideline-recommended approach prioritizes SSRIs and SNRIs as first-line monotherapy:

• Escitalopram and sertraline are the preferred first-line agents due to their established efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms 1, 2
• Venlafaxine (75-225 mg/day) and duloxetine (60-120 mg/day) are effective SNRI alternatives for generalized anxiety disorder 1
• Japanese guidelines specifically recommend SSRIs (fluvoxamine, paroxetine, escitalopram) or venlafaxine for social anxiety disorder with weak but consistent evidence (GRADE 2C) 3

Gabapentin's Limited Role

Gabapentin is explicitly positioned as a second-line option, not monotherapy:

• Pregabalin/gabapentin can be considered only when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain conditions 1
• The systematic review evidence shows gabapentin may have benefit for some anxiety disorders, but notably there are no studies for generalized anxiety disorder 4
• Available evidence consists primarily of case reports and open-label trials rather than randomized controlled trials, representing lower quality evidence 5, 6, 4

Why Gabapentin Fails as First-Line Monotherapy

The evidence base is insufficient for monotherapy use:

• No randomized controlled trials exist for gabapentin in generalized anxiety disorder 5
• The literature suggests gabapentin is effective as an adjunctive medication rather than monotherapy 6
• Only 34 clinical trials investigating psychiatric disorders with gabapentin contained quality of evidence level II-2 or higher 4
• One positive trial showed efficacy in breast cancer survivors with anxiety, but this represents a specific population, not general anxiety treatment 7

Recommended Treatment Algorithm

For adult patients with anxiety disorders:

1. Start with SSRI monotherapy: Escitalopram 5-10 mg daily or sertraline 25-50 mg daily, titrating gradually over 1-2 weeks 1, 2
2. Allow adequate trial duration: Statistically significant improvement begins at week 2, clinically significant improvement by week 6, maximal benefit by week 12 1
3. If inadequate response after 8-12 weeks: Switch to a different SSRI or SNRI 1
4. Consider gabapentin only after: Multiple SSRI/SNRI trials have failed or are not tolerated, particularly if comorbid pain conditions exist 1

Critical Clinical Pitfalls

• Never use gabapentin as first-line monotherapy when evidence-based treatments (SSRIs/SNRIs) are available and appropriate 1
• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Benzodiazepines should be reserved for short-term use only due to dependence, tolerance, and withdrawal risks 1, 2
• Combining medication with cognitive behavioral therapy provides superior outcomes compared to either treatment alone 1, 2