Gabapentin for Anxiety: What the Research Really Says 

Gabapentin (Neurontin) was originally developed as a muscle relaxant and anti-spasmodic but is now primarily used as an anticonvulsant and adjunct in seizure management [1]. It also shows efficacy in certain neuropathic pain conditions and select psychiatric disorders, though further research is warranted. Importantly, Gabapentin is not FDA-approved for the treatment of anxiety. Its off-label use for anxiety remains controversial, as clinicians balance potential benefits with limited evidence and safety concerns. 

This article reviews gabapentin’s mechanism of action, applications, and associated risks and limitations. This content is intended for educational purposes only; always consult with a qualified medical provider before starting, stopping, or changing any medication. 

What Is Gabapentin, and How Does It Work? 

Gabapentin is an FDA-approved anticonvulsant used for epilepsy and postherpetic neuralgia, though it lacks approval for anxiety or other psychiatric conditions. Its central nervous system depressant effects have prompted off-label use in psychiatric settings, including as adjunct therapy for alcohol withdrawal [1]. 

Gabapentin binds to the alpha-2-delta subunit of voltage-gated calcium channels, reducing calcium influx and subsequent glutamate release. Although it does not act directly on GABA receptors, this inhibition of excitatory signaling may indirectly enhance GABAergic tone, contributing to its anxiolytic-like effects. Additional mechanisms include ERK1/2-mediated downregulation of CaMKII, inhibition of glutamate and NMDA receptor activity, enhanced GABA synthesis, suppression of NF-κB-driven inflammation, and activation of adenosine A1 receptors [2–3]. These pathways—particularly those modulating glutamate, the brain’s primary excitatory neurotransmitter—may underlie gabapentin’s potential in anxiety and neuroinflammatory conditions. 

What Does the Research Say About Gabapentin for Anxiety? 

Gabapentin has demonstrated potential anxiolytic effects in small studies and specific clinical contexts, though high-quality, large-scale trials are lacking. In a randomized controlled trial, gabapentin at doses up to 3600 mg/day significantly improved symptoms of social anxiety disorder (SAD) compared to placebo, generating interest in its off-label use for performance anxiety and stage fright [4]. 

Additional case reports and small trials have explored its use in generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). For example, Berigan (2000) reported reduced nightmares, improved sleep, and decreased anxiety in a PTSD patient treated with gabapentin [5]. However, most of this evidence is anecdotal or observational. A further 2003 case study involving a 37-year-old female with PTSD and depression reported significant reduction in her flashbacks when gabapentin was added in conjunction with her antidepressant [6].  

A 2015 systematic review of 219 studies found limited high-quality evidence supporting gabapentin’s psychiatric use. While some benefit was noted for anxiety disorders and in managing alcohol and opioid withdrawal, findings for PTSD, OCD, depression, and broader substance use disorders were inconclusive [7]. A 2019 review in Frontiers in Psychiatry reinforced these conclusions, emphasizing the need for more rigorous clinical trials [8]. 

Gabapentin has also been evaluated in perioperative settings for its ability to reduce acute preoperative anxiety and postoperative pain. While some trials report short-term anxiolytic effects, these are typically limited to the perioperative period and not generalizable to chronic anxiety management 

How Does It Compare to First-Line Treatments? 

Gabapentin is not a first-line treatment for anxiety. Clinical guidelines typically recommend SSRIs or SNRIs in conjunction with cognitive behavioral therapy (CBT) as these have stronger evidence and regulatory approval [9-11].  

Mindfulness techniques may also be valuable in managing anxiety, in addition to nutrition and lifestyle factors [12].  

A growing body of research suggests that nutrient dense, whole foods supports anxiety by providing the body and brain with the nutrients it needs to function optimally, while also supporting the gut-brain axis, a bidirectional communication system in which the gut microbiota influence neural function through the synthesis of neurotransmitters [13-14].  

Sleep is also essential for modulating anxiety as it supports regulating the body’s systems, including the central nervous system and clearing the body and brain of waste. Circadian rhythm balance— getting exposure to sunlight in the morning and refraining from artificial light towards the end of the day are also important for managing anxiety; as is connection to nature [15-17]; these foundational pillars of health should be also considered in the picture of anxiety.  

However, gabapentin may be considered in the following scenarios: 

Gabapentin may be considered in specific clinical scenarios, particularly when first-line treatments are ineffective or contraindicated: 

• Patients who cannot tolerate SSRIs or SNRIs due to adverse effects 

• Individuals with a history of substance use disorder, where benzodiazepines pose a risk 

• Those with comorbid conditions such as neuropathic pain, fibromyalgia, or insomnia 

• Patients with partial response to standard therapies and persistent somatic anxiety symptoms 

Even in these cases, gabapentin is often used as an adjunct therapy and not a first line treatment for anxiety. Gabapentin should be utilized under close supervision with a qualified health provider following a comprehensive history and closely monitored.  

Safety Concerns and Side Effects 

Gabapentin is generally well-tolerated but carries certain safety concerns. In 2019, the U.S. FDA issued a warning regarding the risk of serious respiratory depression when gabapentin is used concurrently with central nervous system (CNS) depressants such as opioids, or in individuals with underlying respiratory conditions [18].  

Common adverse effects include: 

• Sedation or drowsiness 

• Dizziness and impaired coordination leading to potential falls 

• Peripheral edema 

• Fatigue or generalized weakness 

• Mood alterations, including irritability 

Although gabapentin is not classified as physically addictive in the same manner as opioids or benzodiazepines, long-term use may lead to physiological dependence. Abrupt discontinuation can result in withdrawal symptoms, including rebound anxiety, insomnia, agitation, and flu-like symptoms [19]. A gradual dose taper is recommended to minimize these effects. 

There is increasing concern regarding the misuse of gabapentin, particularly among individuals with a history of substance use disorders. While its abuse potential is lower than that of traditional controlled substances, some reports suggest gabapentin is used to potentiate opioid effects or for self-medication. In response, several U.S. states have reclassified gabapentin as a controlled substance [20]. 

How Long Does Gabapentin Take to Work for Anxiety? 

Gabapentin’s onset of action for anxiety is typically gradual, in contrast to fast-acting anxiolytics like benzodiazepines. Clinical reports suggest some individuals may begin to notice symptom relief within 1 to 2 weeks, though a full therapeutic response may require 4 to 6 weeks. Due to its relatively short half-life, gabapentin generally requires dosing two to three times per day [20]. 

Response to gabapentin varies considerably among individuals. While some patients report meaningful reductions in anxiety symptoms, others may experience minimal benefit or adverse effects. This variability highlights the importance of individualized treatment under the guidance of a knowledgeable healthcare provider. 

Is Gabapentin Right for You? 

Gabapentin may be considered in select clinical scenarios, such as: 

• Individuals with both an anxiety disorder and neuropathic pain 

• Patients with a history of alcohol use disorder who also experience anxiety 

• Cases of treatment-resistant anxiety where first-line therapies have been ineffective 

However, gabapentin is not recommended as a first-line or stand-alone treatment for moderate to severe anxiety. It should not replace evidence-based psychotherapies or guideline-supported pharmacologic treatments. Inappropriate use may delay effective care or increase the risk of adverse effects [7-8]. 

Patients considering gabapentin should consult a qualified psychiatric provider. A thorough clinical evaluation is essential to assess the appropriateness of gabapentin based on individual risk factors, treatment history, and therapeutic goals. 

Understanding Off-Label Use 

Off-label prescribing refers to the use of an FDA-approved medication for an indication not included in its official labeling. This practice is legal and relatively common in psychiatry, where patient presentations often extend beyond the scope of approved treatments [7]. 

However, off-label use requires heightened clinical responsibility. Prescribers must: 

• Clearly disclose that the medication is not FDA-approved for the intended condition 

• Discuss the quality and limitations of the supporting evidence 

• Monitor closely for side effects, misuse, and therapeutic response 

• Be aware of other medications you are on to assess for any potential adverse drug interactions 

Patients should always be part of this conversation, informed of risks, available alternatives, and actively involved in decisions regarding their care and how they feel in response to the medication.  

FAQs 

Is gabapentin FDA-approved for anxiety? 

No. Gabapentin is approved only for epilepsy and postherpetic neuralgia. Any psychiatric use, including for anxiety, is off-label, therefore not FDA approved [18]. 

Is it safer than benzodiazepines? 

Gabapentin is generally associated with a lower risk of dependence and sedation at therapeutic doses. However, cases of misuse and withdrawal have been reported, particularly at high doses or with prolonged use [20]. It carries different—though not necessarily lesser—risks compared to benzodiazepines. Misuse can also be very dangerous and in conjunction with certain other medications.  

Can it be used long term? 

While gabapentin is sometimes used long term, there is limited evidence on its long-term use for anxiety. Regular monitoring is recommended to assess efficacy, tolerance, side effects, and risk of dependence [7,18]. 

Should I ask my doctor about it? 

Gabapentin is considered a third line treatment for anxiety or an adjunctive (define this) option under the guidance of a qualified medical provider [8].Gabapentin may be considered if other primary and secondary treatments (e.g., CBT, SSRIs, SNRIs,) are ineffective or poorly tolerated. It is also important to be mindful of foundational lifestyle factors that support regulation of anxiety (e.g., sleep, nutrition, stress, movement, nature, safe connections).  

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References 

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[2]: Rusciano D. (2024). Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases. Pharmaceuticals (Basel). May 11;17(5):623. doi: 10.3390/ph17050623. PMID: 38794193; PMCID: PMC11124268. 

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[13]: Dal N, Bilici S. (2024). An Overview of the Potential Role of Nutrition in Mental Disorders in the Light of Advances in Nutripsychiatry. Curr Nutr Rep.  Jun;13(2):69-81. doi: 10.1007/s13668-024-00520-4. Epub 2024 Feb 8. PMID: 38329691; PMCID: PMC11133159. 

[14]:Merino Del Portillo M, Clemente-Suárez VJ, Ruisoto P, Jimenez M, Ramos-Campo DJ, Beltran-Velasco AI, Martínez-Guardado I, Rubio-Zarapuz A, Navarro-Jiménez E, Tornero-Aguilera JF. (2024). Nutritional Modulation of the Gut-Brain Axis: A Comprehensive Review of Dietary Interventions in Depression and Anxiety Management. Metabolites.  Oct 14;14(10):549. doi: 10.3390/metabo14100549. PMID: 39452930; PMCID: PMC11509786. 

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[16]: Morris SMJ, Kountouriotis GK. (2024) Anxiety in emerging adults: The role of chronotype, emotional competence, and sleep quality. Chronobiol Int. Dec;41(12):1566-1573. doi: 10.1080/07420528.2024.2429661. Epub 2024 Nov 18. PMID: 39555654. 

[17] Chang CC, Lin BB, Feng X, Andersson E, Gardner J, Astell-Burt T. (2024). A lower connection to nature is related to lower mental health benefits from nature contact. Sci Rep. Mar 20;14(1):6705. doi: 10.1038/s41598-024-56968-5. PMID: 38509180; PMCID: PMC10954714. 

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 [19]: U.S. FDA. (2019). FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin 

 [20]: Mersfelder TL, Nichols WH. (2016). Gabapentin: Abuse, Dependence, and Withdrawal. Annals of Pharmacotherapy;50(3):229-233. https://journals.sagepub.com/doi/abs/10.1177/1060028015620800