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.

What is neuropathic pain?

Neuropathic pain can happen if your nervous system is damaged or not working correctly. You can feel pain from any of the various levels of the nervous system—the peripheral nerves, the spinal cord and the brain. Together, the spinal cord and the brain are known as the central nervous system. Peripheral nerves are the ones that are spread throughout the rest of your body to places likes organs, arms, legs, fingers and toes.

Damaged nerve fibers send the wrong signals to pain centers. Nerve function may change at the site of the nerve damage, as well as areas in the central nervous system (central sensitization).

Neuropathy is a disturbance of function or a change in one or several nerves. Diabetes is responsible for about 30% of neuropathy cases. It is not always easy to tell the source of the neuropathic pain. There are hundreds of diseases that are linked to this kind of pain.

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 .

Gabapentin Usage for Alcohol disorder and Alcohol withdrawal

Alcohol use disorder, moderate to severe (alternative agent)

Data from randomized, double-blind, placebo-controlled studies support the use of gabapentin in the maintenance of abstinence in patients with alcohol use disorder.

Based on the American Psychiatric Association (APA) guidelines for the pharmacological treatment of patients with alcohol use disorder, gabapentin is suggested for patients with alcohol use disorder (moderate to severe) who want to decrease or abstain from use of alcohol and either prefer gabapentin or are unable to tolerate or are unresponsive to naltrexone and acamprosate .

Based on the VA/DoD clinical practice guideline for the management of substance use disorders, gabapentin given for moderate to severe alcohol use disorder is effective and suggested when first-line pharmacotherapy is contraindicated or ineffective.

Alcohol withdrawal, mild (alternative agent)

Data from a randomized, double-blind, active-controlled study support the use of gabapentin in the treatment of alcohol withdrawal.

Based on the VA/DoD clinical practice guideline for the management of substance use disorders, gabapentin given for mild alcohol withdrawal is effective and suggested when the risk of benzodiazepines outweigh the benefits (eg, inadequate monitoring available, abuse liability, contraindication, adverse reaction).

Gabapentin Pharmacology

Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis or uptake of GABA.

High affinity gabapentin binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit.

Gabapentin 800mg
Gabapentin 800mg

This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception.

Absorption

Variable, from proximal small bowel by L-amino transport system; saturable process; dose-dependent

Vd: 58 ± 6 L; CSF concentrations are ~20% of plasma concentrations

Metabolism

Not metabolized

Excretion

Proportional to renal function; urine (as unchanged drug)

Clearance: Apparent oral clearance is directly proportional to CrCl: Clearance in infants is highly variable; oral clearance (per kg) in children <5 years of age is higher than in children ≥5 years of age

Time to Peak

Immediate release: Infants 1 month to Children 12 years: 2 to 3 hours; Adults: 2 to 4 hours; Extended release: 8 hours

Half-Life Elimination

Infants 1 month to Children 12 years: 4.7 hours

Adults, normal: 5 to 7 hours; increased half-life with decreased renal function; anuric adult patients: 132 hours; adults during hemodialysis: 3.8 hours

Protein Binding

<3%