eMedExpert Home > Medications Facts > Gabapentin (Neurontin)

Gabapentin was originally discovered over 40 years ago by the Japanese, who initially, were looking for an antispasmodic or muscle relaxant. It was later sold to Parke-Davis (Warner-Lambert, which merged with Pfizer in 2000), who discovered its effectiveness for use in treating epileptics. During their initial clinical studies, Neurontin (Gabapentin) was given in low doses and therefore efficacy was established as an add-on. In other words, the patient was first given another anti-convulsant, and then Neurontin (Gabapentin) was added. Another study, being done at this time, but as yet incomplete, will establish Neurontin as a mono therapy. Neurontin is used by some doctors in doses up to 6,000 mg per day. There is, as yet, no generic form of Neurontin.

• Postherpetic neuralgia
• Epilepsy
  Adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy
  Adjunctive therapy in the treatment of partial seizures in pediatric patients age 3–12 years.

• fibromyalgia 5
• bipolar disorder 8, 30
• postoperative analgesic 9
• migraine prophylaxis 10, 11
• chronic daily headache 31
• postmenopausal hot flashes 12
• interstitial cystitis (IC) 13
• painful diabetic neuropathy 14, 15
• social phobia 16
• depression 18
• panic disorder 19
• essential tremor 20
• generalized tonic-clonic seizures
• restless leg syndrome (RLS) 21, 22
• insomnia 23
• posttraumatic stress disorder (PTSD) 17
• irritable bowel syndrome (IBS) 24
• trigeminal neuralgia 25
• neuropathic pain
• alcohol withdrawal 26

Gabapentin for Fibromyalgia
Gabapentin (1200-2400 mg per day) is safe and effective for the treatment of pain and other symptoms associated with fibromyalgia. In a 12-week, randomized, double-blind study a significantly greater proportion of gabapentin-treated patients achieved response than placebo-treated patients (51% versus 31%). Gabapentin compared with placebo also significantly improved the BPI average pain interference score, the Fibromyalgia Impact Questionnaire total score, the Clinical Global Impression of Severity, the Patient Global Impression of Improvement, the Medical Outcomes Study Sleep Problems Index , but not the mean tender point pain threshold or the Montgomery Asberg Depression Rating Scale 5.

Gabapentin for Bipolar disorder
Evidence suggests that it may have mood-stabilizing and possibly antidepressant properties in bipolar depression. However, its off-label use for bipolar disorder is increasingly controversial.

Gabapentin may have a role as adjunctive agent in the treatment of patients with bipolar disorders when complicated by co-morbid anxiety disorder or substance abuse 29.

Small, randomized clinical trial comparing the prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute efficacy, treatment with gabapentin might provide some benefit on the long-term outcome of bipolar disorder 3.

In small, uncontrolled, heterogeneous study gabapentin, either alone or as an adjunct, appeared moderately effective for depressive and manic symptoms 28.

The findings of placebo-controlled study did not demonstrate that gabapentin is an effective adjunctive treatment when administered to outpatients with bipolar disorder 4.

Gabapentin for Migraine
There is fair evidence of gabapentin effectiveness for prophylactic treatment of migraine. Two clinical trials have found gabapentin (Neurontin) to be effective at dosages of 1,200 to 2,400 mg per day. It reduces headache frequency and use of symptomatic drugs.

The double-blind study of 143 patients evaluated gabapentin for migraine prophylaxis. Only 16% of the patients taking placebo had a 50% or greater reduction in the 4-week migraine rate, compared with 46% of the patients taking gabapentin. The most common side effects in the gabapentin group were somnolence (24.5%) and dizziness (22.4%). Gabapentin appeared to be well tolerated and effective as migraine prophylaxis 10.

Gabapentin for restless leg syndrome (RLS)
Restless legs syndrome is a disorder characterized by sensory and motor symptoms in the legs that is best treated with dopaminergic drugs and opiates. RLS is a disorder that is often difficult to treat. Gabapentin provides a well-tolerated and effective treatment of RLS. This medication improves sensory and motor symptoms in RLS and also improves sleep.

In clinical study gabapentin was associated with reduced symptoms on RLS Rating Scale, Clinical Global Impression, pain analogue scale, and Pittsburgh Sleep Quality Index. Sleep studies showed a significantly reduced periodic leg movements during sleep and improved sleep architecture (increased total sleep time, sleep efficiency, and slow wave sleep, and decreased stage 1 sleep). Patients whose symptoms included pain benefited most from gabapentin 22.

• Advantages:
• lack of cardiovascular or respiratory side effects
• very good tolerability
• benign side-effect profile
• lack of hepatic metabolism
• lack of liver and enzyme-inducing or -inhibiting effects
• absence of drug interactions with other AEDs
• generic availability
• liquid formulation
• may be effective in treatment-resistant depression 18 and refractory bipolar disorder 30
• can be rapidly titrated 32
• Disadvantages:
• delay in response due to need for dosage titration
• dosage adjustment is required in patients with renal impairment
• frequent dosing regimen due to the short half-life
• low potency as antiepileptic medication, not effective for all types of seizures 34, 35
• high rate of somnolence and dizziness 33
• weight gain 7
• possible withdrawal syndrome after discontinuation 8

The chemical structure of gabapentin (Neurontin) is derived by addition of a cyclohexyl group to the backbone of neurotransmitter GABA (gamma-aminobutyric acid).

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

Analgesic action
The mechanism by which Gabapentin exerts its analgesic action is unknown, but in animal models of analgesia, Gabapentin prevents allodynia (pain-related behavior in response to a normally innocuous stimulus) and hyperalgesia (exaggerated response to painful stimuli). In particular, Gabapentin prevents pain-related responses in several models of neuropathic pain in rats or mice (e.g. spinal nerve ligation models, streptozocin-induced diabetes model, spinal cord injury model, acute herpes zoster infection model). Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan footpad test, late phase of formalin test). Gabapentin did not alter immediate pain-related behaviors (rat tail flick test, formalin footpad acute phase, acetic acid abdominal constriction test, footpad heat irradiation test). The relevance of these models to human pain is not known.

Anticonvulsant action
The mechanism by which Gabapentin exerts its anticonvulsant action is unknown, but in animal test systems designed to detect anticonvulsant activity, Gabapentin prevents seizures as do other marketed anticonvulsants. Gabapentin exhibits antiseizure activity in mice and rats in both the maximal electroshock and pentylenetetrazole seizure models and other preclinical models (e.g., strains with genetic epilepsy, etc.). The relevance of these models to human epilepsy is not known.

Gabapentin has no activity at GABAA or GABAB receptors of GABA uptake carriers of brain. Gabapentin interacts with a high-affinity binding site in brain membranes. Gabapentin crosses several lipid membrane barriers via system L amino acid transporters. In vitro, gabapentin modulates the action of the GABA synthetic enzyme, glutamic acid decarboxylase (GAD) and the glutamate synthesizing enzyme, branched-chain amino acid transaminase. Results with human and rat brain NMR spectroscopy indicate that gabapentin increases GABA synthesis. Gabapentin increases non-synaptic GABA responses from neuronal tissues in vitro. In vitro, gabapentin reduces the release of several mono-amine neurotransmitters. Gabapentin prevents pain responses in several animal models of hyperalgesia and prevents neuronal death in vitro and in vivo with models of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Gabapentin is also active in models that detect anxiolytic activity. Although gabapentin may have several different pharmacological actions, it appears that modulation of GABA synthesis and glutamate synthesis may be important 6.

The elimination half-life is 5-7 hours and is unaltered by dose or following multiple dosing. It usually takes 2 days for Gabapentin to leave the system.

While some people notice the antimanic and antidepressant effects within a week or two of starting treatment, others have to take a therapeutic amount of gabapentin for up to a month before being aware of a significant amount of improvement.

Gabapentin should be tapered off gradually. Abrupt discontinuation of gabapentin is associated with development of a syndrome resembling alcohol or benzodiazepine withdrawal 8.

Though gabapentin is not a controlled substance, it does produce psychoactive effects. It is regarded as having little or no abuse potential.

• Gabapentin (Neurontin) versus Other Medications

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