Gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication used to treat neuropathic pain and partial seizures of epilepsy. Gabapentin is a
central nervous system depressant and derivative of GABA. It is used for the treatment of neuropathic pain caused by diabetic neuropathy, postherpetic neuralgia, and central pain. It is moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit.
Gabapentin acts by decreasing activity of the α2δ-1 protein, coded by the CACNA2D1 gene, first known as an auxiliary subunit of voltage-gated calcium channels. By binding to α2δ-1, gabapentin reduces the release of excitatory neurotransmitters and as a result, reduces excess excitation of neuronal networks in the spinal cord and brain. Sleepiness and dizziness are the most common side effects. Serious side effects include respiratory depression and allergic reactions. On December 16, 2008, the FDA issued gabapentin a class warning for an increased risk of suicide. Approximately two years after this pronouncement, a pharmacoepidemiologic study was conducted that showed there was no outstanding difference in suicide attempt rates between pre and post gabapentin prescription groups.
Gabapentin was first approved for use in the United Kingdom in 1993. It has been available as a generic medication in the United States since 2004. It is the first of several other drugs that are similar in structure and mechanism, called gabapentinoids. In 2023, it was the ninth most commonly prescribed medication in the United States, with more than 45million prescriptions. During the 1990s, Parke-Davis, a subsidiary of Pfizer, used several illegal techniques to encourage physicians in the United States to prescribe gabapentin for unapproved uses. They have paid out millions of dollars to settle lawsuits regarding these activities.
Medical uses
In the US, gabapentin is indicated for the treatment of postherpetic neuralgia; and the adjunctive therapy in the treatment of partial onset seizures without secondary generalization, in people with epilepsy.Gabapentin is recommended for use in focal seizures and neuropathic pain. Gabapentin is prescribed off-label in the US and the UK, for example, for the treatment of non-neuropathic pain, anxiety disorders, sleep problems and bipolar disorder. In recent years, gabapentin has seen increased use, particularly in the elderly. There is concern regarding gabapentin's off-label use due to the lack of strong scientific evidence for its efficacy in multiple conditions, its proven side effects and its potential for misuse and physical/psychological dependency. Some harms, including nervous system harms, have been underreported in published trials of gabapentin, potentially resulting in the underestimation of harms in guidelines for the use of gabapentin.
Seizures
Gabapentin is approved for the treatment of focal seizures; however, it is not effective for generalized epilepsy.Neuropathic pain
Gabapentin is recommended as a first-line treatment for chronic neuropathic pain by various medical authorities. This is a general recommendation applicable to all neuropathic pain syndromes except for trigeminal neuralgia, where it may be used as a second- or third-line agent.Regarding the specific diagnoses, a systematic review has found evidence for gabapentin to provide pain relief for some people with postherpetic neuralgia and diabetic neuropathy. Gabapentin is approved for the former indication in the US. In addition to these two neuropathies, European Federation of Neurological Societies guideline notes gabapentin effectiveness for central pain. A combination of gabapentin with an opioid or nortriptyline may work better than either drug alone.
Evidence finds little or no benefit and significant risk in those with chronic low back pain or sciatica. Gabapentin is not effective in HIV-associated sensory neuropathy and neuropathic pain due to cancer.
Anxiety
There is a small amount of research on the use of gabapentin for the treatment of anxiety disorders.Gabapentin is effective for the long-term treatment of social anxiety disorder and in reducing preoperative anxiety.
In a controlled trial of breast cancer survivors with anxiety, and a trial for social phobia, gabapentin significantly reduced anxiety levels.
For panic disorder, gabapentin has produced mixed results.
Sleep
Gabapentin is effective in treating sleep disorders such as insomnia and restless legs syndrome that are the result of an underlying illness, but comes with some risk of discontinuation and withdrawal symptoms after prolonged use at higher doses.Gabapentin enhances slow-wave sleep in people with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal.
Drug dependence
Gabapentin is moderately effective in reducing the symptoms of alcohol withdrawal and associated craving. The evidence in favor of gabapentin is weak in the treatment of alcoholism: it does not contribute to the achievement of abstinence, and the data on the relapse of heavy drinking and percent of days abstinent do not robustly favor gabapentin; it only decreases the percent days of heavy drinking.Gabapentin is ineffective in cocaine dependence and methamphetamine use, and it does not increase the rate of smoking cessation. While some studies indicate that gabapentin does not significantly reduce the symptoms of opiate withdrawal, there is increasing evidence that gabapentinoids are effective in controlling some of the symptoms during opiate detoxification. A clinical study in Iran, where heroin dependence is a significant social and public health problem, showed gabapentin produced positive results during an inpatient therapy program, particularly by reducing opioid-induced hyperalgesia and drug craving. There is insufficient evidence for its use in cannabis dependence.
Other
Gabapentin is recommended as a first-line treatment of the acquired pendular nystagmus, torsional nystagmus, and infantile nystagmus; however, it does not work in periodic alternating nystagmus.Gabapentin decreases the frequency of hot flashes in both menopausal women and people with breast cancer. However, antidepressants have similar efficacy, and treatment with estrogen more effectively prevents hot flashes.
Gabapentin reduces spasticity in multiple sclerosis and is prescribed as one of the first-line options. It is an established treatment of restless legs syndrome. Gabapentin alleviates itching in kidney failure and itching of other causes. It may be an option in essential or orthostatic tremor.
Gabapentin does not appear to provide benefit for bipolar disorder, complex regional pain syndrome, post-surgical pain, or tinnitus, or prevent episodic migraine in adults.
Gabapentin is prescribed off-label as a anxiolytic or anti-anxiety medication, although not as effective as pregabalin in this regard, especially for generalized anxiety disorder, as gabapentin is more effective for social anxiety disorder.
Contraindications
Gabapentin should be used carefully and at lower doses in people with kidney problems due to possible accumulation and toxicity. It is unclear if it is safe during pregnancy or breastfeeding.Side effects
In a systematic review analysing data from five cohort studies having 1,085,488 patients, use of gabapentinoids was associated with an increased risk of thrombotic events as early as three months of use, and with increased risk of cardiovascular events on prolonged use of more than a year duration. Heart failure was not increased with the use of gabapentinoids.Dizziness and somnolence are the most frequent side effects. Fatigue, ataxia, peripheral edema, and nystagmus are also common. A 2017 meta-analysis found that gabapentin also increased the risk of difficulties in mentation and visual disturbances as compared to a placebo. Gabapentin is associated with a weight gain of after 1.5 months of use. Case studies indicate that it may cause anorgasmia and erectile dysfunction, as well as myoclonus that disappear after discontinuing gabapentin or replacing it with other medication. Fever, swollen glands that do not go away, eyes or skin turning yellow, unusual bruises or bleeding, unexpected muscle pain or weakness, rash, long-lasting stomach pain which may indicate an inflamed pancreas, hallucinations, anaphylaxis, respiratory depression, and increased suicidal ideation are rare but serious side effects.