What is the recommended gabapentin dosing regimen for treating anxiety in adults, including starting dose, titration schedule, maximum dose, and adjustments for reduced renal function or older/frail patients?

Gabapentin Is Not Recommended for Anxiety Disorders

Gabapentin lacks FDA approval and high-quality evidence for treating anxiety disorders, and should not be prescribed for this indication. The medication is widely used off-label for psychiatric conditions including anxiety, but this practice is not supported by randomized controlled trials or clinical guidelines 1, 2.

Evidence Base for Anxiety Treatment

Absence of Controlled Trial Data

• There are no randomized controlled trials demonstrating gabapentin's effectiveness for generalized anxiety disorder (GAD), with only isolated case reports available in the literature 3, 1.
• A 2017 case report described dose-response effects in a single 59-year-old woman with GAD, but this anecdotal evidence cannot establish efficacy 3.
• The lack of controlled studies means gabapentin's risk-benefit profile for anxiety remains uncharacterized 1.

Off-Label Use Patterns and Safety Concerns

• Between 2011-2016, only <1% of gabapentin prescriptions in the U.S. were for FDA-approved indications, with 3.5% of off-label visits listing anxiety disorders 2.
• Among off-label gabapentin visits for psychiatric conditions, 58.4% involved concomitant CNS depressant medications, most frequently antidepressants (24.3%), opioids (22.9%), and benzodiazepines (17.3%) 2.
• The FDA has issued warnings about respiratory depression and death when gabapentin is combined with opioids or other CNS depressants—a common scenario in psychiatric practice 2.

Evidence-Based First-Line Treatments for Anxiety

Pharmacologic Options with Proven Efficacy

• Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are consistently beneficial and represent first-line pharmacotherapy for GAD 4.
• Pregabalin (not gabapentin) has short-term trial data for anxiety, though NICE's recommendation is now questioned due to tolerance, dependence, and rising mortality rates 5.
• Buspirone (azapirone), hydroxyzine (antihistamine), and benzodiazepines (short-term only) have established roles in GAD treatment 4.

Critical Distinction: Pregabalin vs. Gabapentin

• Pregabalin has been studied in short-term anxiety trials with marginal superiority over placebo, whereas gabapentin has no such trial data 1, 5.
• Even pregabalin's use for anxiety is now controversial: deaths involving pregabalin in England (244 in 2019) now exceed those from diazepam, fentanyl, tricyclics, or SSRIs, with rates rising steeply over the past decade 5.
• Both gabapentinoids carry risks of tolerance, dependence, addiction, and withdrawal similar to benzodiazepines, leading to their classification as Schedule C controlled substances in the UK 5.

Why Gabapentin Should Not Be Used for Anxiety

Lack of Efficacy Evidence

• The absence of randomized controlled trials means there is no established effective dose, titration schedule, or expected response rate for anxiety 3, 1.
• Novel anxiolytic agents under investigation (glutamate modulators, neuropeptides, cannabinoids) have shown largely negative results in recent trials, with only kava and PH94B showing promise—gabapentin is not among agents with positive data 1.

Unacceptable Safety Profile in Psychiatric Populations

• Psychiatric patients frequently take multiple CNS depressants (antidepressants, benzodiazepines, opioids), creating dangerous synergistic sedation and respiratory depression risk when gabapentin is added 2.
• The 2019 FDA warning specifically addresses this polypharmacy risk, which is the norm rather than the exception in anxiety treatment 2.

Superior Alternatives Exist

• SSRIs and SNRIs have decades of efficacy and safety data, established dosing protocols, and FDA approval for anxiety disorders 4.
• Cognitive-behavioral therapy is effective as first-line treatment and avoids pharmacologic risks entirely 4.
• For patients requiring rapid anxiolysis, benzodiazepines (used judiciously and short-term) or buspirone have known risk-benefit profiles 4.

Common Pitfalls to Avoid

• Do not extrapolate from neuropathic pain data: Gabapentin's efficacy for postherpetic neuralgia and diabetic neuropathy (1800-3600 mg/day) does not predict anxiolytic effects 6, 7.
• Do not assume "off-label use is common" equals "evidence-based": The 2011-2016 data show widespread inappropriate prescribing, not validated practice 2.
• Do not combine gabapentin with benzodiazepines or opioids in anxiety patients—this creates compounded CNS depression without established benefit 2.
• Do not prescribe gabapentin when SSRIs/SNRIs have not been tried: These agents have proven long-term efficacy for the chronic nature of GAD 4.

Recommended Approach for Anxiety Treatment

Start with an SSRI or SNRI as first-line pharmacotherapy, titrating to therapeutic doses over 4-6 weeks while monitoring for response 4. GAD is a chronic illness requiring long-term treatment, and remission typically takes several months to achieve 4. If the patient has comorbid depression (common with GAD), an antidepressant is more likely to succeed than any other agent 4. Reserve benzodiazepines for short-term use during the initial weeks of SSRI/SNRI titration if severe anxiety requires immediate relief 4. Consider buspirone or hydroxyzine as alternatives if SSRIs/SNRIs are contraindicated or poorly tolerated 4.