Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication used to treat neuropathic pain (postherpetic neuralgia) and partial seizures of epilepsy. Gabapentin is a central nervous system (CNS) depressant and derivative of the inhibitory neurotransmitter, 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 binds to α2δ subunits to modulate calcium channel function and neurotransmitter release, weakly affects glutamate signaling pathways, and does not act on GABA receptors. Sleepiness and dizziness are the most common side effects. Serious side effects include extreme sedation, respiratory depression and allergic reactions. In December 2008, the US Food and Drug Administration issued a class-wide warning for gabapentinoids 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 as an 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 (uremic pruritus) 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 an anxiolytic or anti-anxiety medication, although not as effective as pregabalin in this regard, especially for generalized 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 analyzing data from five cohort studies having 1,085,488 patients, use of gabapentinoids (gabapentin and pregabalin) was associated with an increased risk of thrombotic events (deep venous thrombosis and pulmonary thrombo-embolism) 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 (swelling of extremities), 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.
Suicide The gabapentin prescribing information contains a warning of an increased risk of suicidal thoughts and behaviors. The warning is based on a meta-analysis of all approved antiepileptic drugs in 2008, and not with gabapentin alone. According to an experimental meta-analysis of insurance claims databases, gabapentin use is associated with an approximately 40% increased risk of suicide, suicide attempt, and violent death as compared with a reference anticonvulsant drug topiramate. The risk is increased for people with bipolar disorder or epilepsy. Another study has shown an approximately doubled rate of suicide attempts and self-harm in people with bipolar disorder who are taking gabapentin versus those taking lithium. A large Swedish study suggests that gabapentinoids are associated with an increased risk of suicidal behavior, unintentional overdoses, head/body injuries, and road traffic incidents and offenses. On the other hand, a study published by the Harvard Data Science Review found that gabapentin was associated with a significantly reduced rate of suicide.Gibbons, R., Hur, K., Lavigne, J., Wang, J., & Mann, J. J. (2019). Medications and Suicide: High Dimensional Empirical Bayes Screening (iDEAS). Harvard Data Science Review, 1(2). https://doi.org/10.1162/99608f92.6fdaa9de In addition, a 2010 study published by the Pharmacoepidemiology and Drug Safety journal concluded that although there was no significant suicide rate decrease between the pre-prescription window and the post-prescription window for the non-psychiatric population, significant reductions in suicide rates were observed in psychiatric persons.
Respiratory depression Serious breathing suppression, potentially fatal, may occur when gabapentin is taken together with opioids, benzodiazepines, or other depressants, or by people with underlying lung problems such as COPD. Gabapentin and opioids are commonly prescribed or abused together, and research indicates that the breathing suppression they cause is additive. For example, gabapentin use before joint replacement or laparoscopic surgery increased the risk of respiratory depression by 30–60%. A Canadian study showed that use of gabapentin and other gabapentinoids, whether for epilepsy, neuropathic pain or other chronic pain was associated with a 35–58% increased risk for severe exacerbation of pre-existing chronic obstructive pulmonary disease.
Withdrawal and dependence Withdrawal symptoms typically occur 1–2 days after abruptly stopping gabapentin (almost unambiguously due to extended use and during a very short-term rebound phenomenon) similar to, albeit less intense than most benzodiazepines. Agitation, confusion and disorientation are the most frequently reported, followed by gastrointestinal complaints and sweating, and more rare tremor, tachycardia, hypertension and insomnia. In some cases, users experience withdrawal seizures after chronic or semi-chronic use in the absence of periodic cycles or breaks during repeating and consecutive use. All these symptoms subside when gabapentin is re-instated or tapered off gradually at an appropriate rate.