How does Gabapentin Work ?

Gabapentin is a medicine that may be used for the treatment of certain seizure disorders or nerve pain.

How gabapentin works
How gabapentin works

Experts aren’t sure exactly how gabapentin works, but research has shown that gabapentin binds strongly to a specific site (called the alpha2-delta site) on voltage-gated calcium channels. This action is thought to be the mechanism for its nerve-pain relieving and anti-seizure properties.

Gabapentin enacarbil (brand name Horizant) is a prodrug of gabapentin which has been designed to overcome the limitations of gabapentin, such as poor absorption and a short duration of action. Gabapentin enacarbil is effective for restless legs syndrome (RLS) and postherpetic neuralgia (nerve pain that occurs following Shingles).

Gabapentin belongs to the group of medicines known as anticonvulsants.

Gabapentin is used for Restless legs syndrome

Gabapentin in the management of restless legs syndrome (RLS) has been evaluated in small controlled trials, demonstrating benefits compared with placebo. Gabapentin enacarbil is FDA-approved for the treatment of RLS .

The American Academy of Sleep Medicine (AASM) guidelines regarding RLS management consider gabapentin effective based on low-level evidence and note that patients with pain symptoms appeared to benefit most.

The benefit-risk ratio is unclear. The European Federation of Neurological Societies/European Neurological Society/European Sleep Research Society (EFNS/ENS/ESRS) Task Force guidelines consider gabapentin effective for short-term management and possibly effective for long-term management of RLS.

Additional study is needed to establish optimal dosing. Based on the International Restless Legs Syndrome Study Group, European Restless Legs Syndrome Study Group, and RLS Foundation (IRLSSG/EURLSSG/RLS-F) guidelines for the prevention and treatment of dopaminergic augmentation in restless legs syndrome, α2δ ligands (eg, gabapentin) are effective and should be considered for the initial treatment of patients with RLS due to their minimal risk of augmentation.

Additionally, patients who experience augmentation on dopaminergic agents may benefit from a switch to α2δ ligands (eg, gabapentin). However, the guidelines note that long-term studies are needed.

Gabapentin is used for Neuropathic pain (other than postherpetic neuralgia)

In a meta-analysis of trials evaluating the treatment of neuropathic pain, including painful polyneuropathy and spinal cord injury pain, gabapentin was shown to be safe and effective . Data from meta-analyses support the use of immediate-release gabapentin for reducing pain by more than 50% in diabetic neuropathy.

Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy

Data from a limited number of clinical trials support the use of extended-release gabapentin in reducing pain by more than 50% and improving sleep in diabetic neuropathy.

Based on guidelines from the International Association for the Study of Pain (IASP), European Federation of Neurological Societies (EFNS), and Society of Critical Care Medicine (SCCM), gabapentin is effective and recommended for the management of peripheral neuropathy .

Based on guidelines from the EFNS, IASP, and National Institute for Health and Care Excellence (NICE), gabapentin is effective and recommended as first-line therapy, supported by strong evidence, in the management of diabetic neuropathy.

The IASP guidelines recommend both immediate- and extended-release gabapentin . In contrast, a guideline from the American Academy of Neurology (AAN), American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation states that gabapentin is probably effective and should be considered an alternative treatment for painful diabetic neuropathy based on limited benefit in 2 controlled trials.

Similarly, a position statement from the American Diabetes Association (ADA) recommends gabapentin as a second-line option .