Gabapentin, most commonly known by the brand name Neurontin, belongs to a class of medications called anticonvulsants. The drug was originally developed as a derivative of the naturally occurring brain chemical gamma-aminobutyric acid (GABA). It received initial approval from the U.S. Food and Drug Administration (FDA) for managing partial seizures in epilepsy. Approved uses later expanded to include the treatment of neuropathic pain, such as postherpetic neuralgia (pain following a shingles infection).
How Gabapentin Affects the Central Nervous System
Gabapentin is structurally similar to the inhibitory neurotransmitter GABA, but it does not bind to GABA receptors. Instead, the drug binds with high affinity to the alpha-2-delta subunit of voltage-gated calcium channels (VGCCs) found on nerve cells in the central nervous system. Binding to this subunit reduces the movement of these calcium channels to the nerve cell membrane.
This reduction in channel density decreases the influx of calcium ions into the nerve ending. Since calcium influx is necessary for releasing chemical messengers, this action dampens the excessive release of excitatory neurotransmitters, such as glutamate. This inhibitory effect on neuronal hyperexcitability is thought to be the basis for the drug’s anti-seizure, pain-relieving, and calming properties, suggesting it stabilizes overactive neural circuits contributing to anxiety.
Clinical Evidence of Efficacy for Anxiety
The clinical evidence supporting gabapentin’s use for primary anxiety disorders is mixed and less robust than for established treatments. For Generalized Anxiety Disorder (GAD), there are no large-scale, randomized controlled trials demonstrating broad efficacy. Evidence consists mainly of smaller studies and case reports suggesting benefit, often in patients who have not responded to first-line agents.
Gabapentin has shown more consistent results in specific contexts, including treating social anxiety disorder and reducing anxiety experienced by breast cancer survivors. It has also been used successfully to reduce preoperative anxiety before medical procedures. However, clinical trial results for other conditions, such as panic disorder, have been inconsistent.
Gabapentin is not typically recommended as a first-line medication; standard treatments like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are preferred due to stronger evidence. Gabapentin is often reserved as a second or third-line option for individuals who cannot tolerate or do not respond to these conventional antidepressants. It is particularly valuable for patients whose anxiety co-occurs with Substance Use Disorders, especially Alcohol Use Disorder, as it can address both conditions simultaneously.
Prescribing Status and Off-Label Use
Gabapentin is not FDA-approved for treating any primary anxiety disorder. Its use for anxiety is considered “off-label,” meaning physicians prescribe it outside of its official, regulatory-approved indications. Off-label prescribing is a legal and common practice in medicine, especially when standard treatments are unsuccessful or contraindicated.
Physicians often choose gabapentin off-label due to its perceived safety profile compared to other anxiety medications, particularly benzodiazepines. Unlike benzodiazepines, gabapentin is not associated with the same high risk of abuse, physical dependence, or toxic interaction with alcohol. This makes it a preferred option for individuals with a history of substance abuse. When prescribing off-label, the physician must inform the patient that the use is not officially approved and explain the rationale.
Practical Considerations for Treatment
Patients beginning treatment should be aware of common side effects, including dizziness, drowsiness, and issues with coordination. These effects are minimized by starting the medication at a low dose and gradually increasing it, a process known as titration. Due to the drug’s non-linear absorption, initial doses are often small (100 to 300 milligrams), with the target dose typically reached over several days to weeks.
A common therapeutic range for anxiety is between 900 and 1800 milligrams per day, divided into two or three doses. Even when used as prescribed, the body can develop a physical dependence on gabapentin. Therefore, the medication must never be stopped suddenly. Abrupt cessation can trigger a withdrawal syndrome, which may include severe symptoms like rebound anxiety, agitation, insomnia, and in extreme cases, seizures. Discontinuing gabapentin must be done slowly under medical supervision, often by reducing the dose gradually over several weeks to allow the nervous system to readjust safely.