Gabapentin, sold under the brand nameNeurontin among others, is ananticonvulsant medication primarily used to treatneuropathic pain and also forpartial seizures^[10][7] ofepilepsy. It is a commonly used medication for the treatment of neuropathic pain caused bydiabetic neuropathy,postherpetic neuralgia, andcentral pain.^[11] It is moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit.^[12]

Gabapentin

Clinical data
Trade names	Neurontin, others[1]
Other names	CI-945; GOE-3450; DM-1796 (Gralise)
AHFS/Drugs.com	Monograph
MedlinePlus	a694007
License data	US DailyMed: Gabapentin
Pregnancy category	AU: B1[2]
Dependence liability	Physical: High[3] Psychological: Moderate
Addiction liability	Low[4]
Routes of administration	By mouth
Drug class	Gabapentinoid
ATC code	N02BF01 (WHO)
Legal status
Legal status	AU:S4 (Prescription only)[5] BR:Class C1 (Other controlled substances)[6] CA: ℞-only UK:Class C US: Rx-only, schedule 5 in select states[7]
Pharmacokinetic data
Bioavailability	27–60% (inversely proportional to dose; a high-fat meal also increases bioavailability)[8][9]
Protein binding	Less than 3%[8][9]
Metabolism	Not significantly metabolized[8][9]
Eliminationhalf-life	5 to 7 hours[8][9]
Excretion	Kidney[8][9]
Identifiers
IUPAC name 2-[1-(Aminomethyl)cyclohexyl]acetic acid
CAS Number	60142-96-3 Y
PubChemCID	3446
IUPHAR/BPS	5483
DrugBank	DB00996 Y
ChemSpider	3328 Y
UNII	6CW7F3G59X
KEGG	D00332 Y
ChEBI	CHEBI:42797 Y
ChEMBL	ChEMBL940 Y
PDB ligand	GBN (PDBe,RCSB PDB)
CompTox Dashboard(EPA)	DTXSID0020074
ECHA InfoCard	100.056.415
Chemical and physical data
Formula	C9H17NO2
Molar mass	171.240 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(O)CC1(CN)CCCCC1
InChI InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12) Y Key:UGJMXCAKCUNAIE-UHFFFAOYSA-N Y
(verify)

Gabapentin, like othergabapentinoid drugs, acts by decreasing activity of theα₂δ-1 protein, coded by the CACNA2D1 gene, first known as an auxiliary subunit ofvoltage gated calcium channels.^[13][14][15] However, see Pharmacodynamics, below. By binding to α₂δ-1, gabapentin reduces the release of excitatoryneurotransmitters (primarilyglutamate) and as a result, reduces excess excitation of neuronal networks in thespinal cord and brain. Sleepiness anddizziness are the most commonside effects. Serious side effects includerespiratory depression, andallergic reactions.^[7] As with all other antiepileptic drugs approved by theFDA, gabapentin is labeled for an increased risk ofsuicide. Lower doses are recommended in those withkidney disease.^[7]

Gabapentin was first approved for use in the United Kingdom in 1993.^[16] It has been available as ageneric medication in the United States since 2004.^[17] It is the first of several other drugs that are similar in structure and mechanism, calledgabapentinoids. In 2022, it was the tenth most commonly prescribed medication in the United States, with more than 40 million prescriptions.^[18][19] During the 1990s,Parke-Davis, a subsidiary ofPfizer, used a number of illegal techniques to encouragephysicians in the United States to prescribe gabapentin forunapproved uses.^[20] They have paid out millions of dollars to settle lawsuits regarding these activities.^[21]

Gabapentin is recommended for use infocal seizures andneuropathic pain.^[7][10] Gabapentin is prescribedoff-label in the US and the UK,^[22][23] for example, for the treatment of non-neuropathic pain,^[22]anxiety disorders, sleep problems andbipolar disorder.^[24] In recent years, gabapentin has seen increased use, particularly in the elderly.^[25] 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.^[26][27][28] 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.^[29]

Gabapentin is approved for the treatment of focal seizures;^[30] however, it is not effective forgeneralized epilepsy.^[31]

Gabapentin is recommended as a first-line treatment for chronic neuropathic pain by various medical authorities.^{[10][11][32][33]} This is a general recommendation applicable to all neuropathic pain syndromes except fortrigeminal neuralgia, where it may be used as a second- or third-line agent.^[11][33]

Regarding the specific diagnoses, a systematic review has found evidence for gabapentin to provide pain relief for some people withpostherpetic neuralgia anddiabetic neuropathy.^[12] Gabapentin is approved for the former indication in the US.^[7] In addition to these two neuropathies,European Federation of Neurological Societies guideline notes gabapentin effectiveness forcentral pain.^[11] A combination of gabapentin with anopioid ornortriptyline may work better than either drug alone.^[11][33]

Gabapentin shows substantial benefit (at least 50% pain relief or a patient global impression of change (PGIC) "very much improved") for neuropathic pain (postherpetic neuralgia or peripheral diabetic neuropathy) in 30–40% of subjects treated as compared to those treated withplacebo.^[12]

Evidence finds little or no benefit and significant risk in those with chroniclow back pain orsciatica.^[34][35] Gabapentin is not effective inHIV-associatedsensory neuropathy^[36] and neuropathic pain due tocancer.^[37]

There is a small amount of research on the use of gabapentin for the treatment of anxiety disorders.^[38][39]

Gabapentin is effective for the long-term treatment ofsocial anxiety disorder and in reducingpreoperative anxiety.^[26][27]

In a controlled trial of breast cancer survivors with anxiety,^[39] and a trial for social phobia,^[38] gabapentin significantly reduced anxiety levels.

Forpanic disorder, gabapentin has produced mixed results.^[39][38][27]

Gabapentin is effective in treating sleep disorders such as insomnia andrestless legs syndrome that are the result of an underlying illness, but comes with some risk ofdiscontinuation andwithdrawal symptoms after prolonged use at higher doses.^[40]

Gabapentin enhancesslow-wave sleep in people with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneousarousal.^[41]

Gabapentin is moderately effective in reducing the symptoms ofalcohol withdrawal and associated craving.^[42][43][44] The evidence in favor of gabapentin is weak in the treatment ofalcoholism: 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.^[45]

Gabapentin is ineffective in cocaine dependence and methamphetamine use,^[46] and it does not increase the rate ofsmoking cessation.^[47] While some studies indicate that gabapentin does not significantly reduce the symptoms ofopiate 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-inducedhyperalgesia anddrug craving.^[48][46] There is insufficient evidence for its use incannabis dependence.^[49]

Gabapentin is recommended as a first-line treatment of the acquiredpendular nystagmus, torsional nystagmus, and infantile nystagmus; however, it does not work in periodic alternating nystagmus.^[50][51][52]

Gabapentin decreases the frequency ofhot flashes in both menopausal women and people with breast cancer. However, antidepressants have similar efficacy, and treatment withestrogen more effectively prevents hot flashes.^[53]

Gabapentin reducesspasticity inmultiple sclerosis and is prescribed as one of the first-line options.^[54] It is an established treatment ofrestless legs syndrome.^[55] Gabapentin alleviates itching in kidney failure (uremic pruritus)^[56][57] and itching of other causes.^[58] It may be an option inessential ororthostatic tremor.^[59][60][61]

Gabapentin does not appear to provide benefit forbipolar disorder,^[27][43][62]complex regional pain syndrome,^[63] post-surgical pain,^[64] ortinnitus,^[65] or preventepisodic migraine in adults.^[66]

Gabapentin should be used carefully and at lower doses in people withkidney problems due to possible accumulation and toxicity. It is unclear if it is safe duringpregnancy orbreastfeeding.^[7]

Dizziness andsomnolence are the most frequentside effects.^[7]Fatigue,ataxia,peripheral edema (swelling of extremities), andnystagmus are also common.^[7] A 2017 meta-analysis found that gabapentin also increased the risk of difficulties inmentation and visual disturbances as compared to a placebo.^[67] Gabapentin is associated with a weight gain of 2.2 kg (4.9 lb) after 1.5 months of use.^[68] Case studies indicate that it may causeanorgasmia anderectile dysfunction,^[69] as well asmyoclonus^[70][71] 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 aninflamed pancreas,hallucinations,anaphylaxis,respiratory depression, and increasedsuicidal ideation are rare but serious side effects.^[72]

As with all antiepileptic drugs approved in the US, gabapentin label contains a warning of an increased risk of suicidal thoughts and behaviors.^[7] This warning is based on a meta-analysis of all approved antiepileptic drugs in 2008, and not with gabapentin alone.^[73] According to an experimental meta-analysis of insurance claims database, gabapentin use is associated with about 40% increased risk ofsuicide,suicide attempt and violent death as compared with a referenceanticonvulsant drugtopiramate. The risk is increased for people withbipolar disorder orepilepsy.^[73] Another study has shown an approximately doubled rate of suicide attempts andself-harm in people with bipolar disorder who are taking gabapentin versus those takinglithium.^[74] A large Swedish study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences.^[75] 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.^[76]

Serious breathing suppression, potentially fatal, may occur when gabapentin is taken together withopioids,benzodiazepines, or otherdepressants, or by people with underlying lung problems such asCOPD.^[77] Gabapentin and opioids are commonly prescribed or abused together, and research indicates that the breathing suppression they cause is additive. For example, gabapentin use beforejoint replacement orlaparoscopic surgery increased the risk ofrespiratory depression by 30–60%.^[77] A Canadian study showed that use of gabapentin and other gabapentinoids, whether forepilepsy,neuropathic pain or other chronic pain was associated with a 35–58% increased risk for severe exacerbation of pre-existingchronic obstructive pulmonary disease.^[78]

Withdrawal symptoms typically occur 1–2 days after abruptly stopping gabapentin (almost unambiguously due to extended use and during a very short-termrebound phenomenon) — similar to, albeit less intense than most benzodiazepines.^[79] Agitation, confusion and disorientation are the most frequently reported, followed by gastrointestinal complaints and sweating, and more raretremor,tachycardia,hypertension andinsomnia.^[79] 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.^[80] All these symptoms subside when gabapentin is re-instated^[79] ortapered off gradually at an appropriate rate.^{[citation needed]}

On its own, gabapentin appears to not have a substantial addictive power. In human and animal experiments, it shows limited to norewarding effects. The vast majority of people abusing gabapentin are current or former abusers of opioids or sedatives.^[80] In these persons, gabapentin can boost the opioid "high" as well as decrease commonly experienced opioid-withdrawal symptoms such as anxiety.^[81]

Through excessive ingestion, accidental or otherwise, persons may experience overdose symptoms including drowsiness, sedation, blurred vision, slurred speech,somnolence, uncontrollable jerking motions, and anxiety. A very high amount taken is associated with breathing suppression, coma, and possibly death, particularly if combined withalcohol oropioids.^[80][82]

Gabapentin, preventsseizures in adose-related manner in several laboratoryanimal models.^[83] These models include spinal extensor seizures from low-intensity electroshock to theforebrain in mice, maximal electroshock in rats, spinal extensor seizures in DBA/2 mice with a genetic sensitivity to seizures induced by loud noise, and in rats "kindled" to producefocal seizures by repeated prior electrical stimulation of thehippocampus. Gabapentin slightly increased spontaneousabsence-like seizures in a genetically susceptible strain recorded withelectroencephalography. All of these effects of gabapentin were seen at dosages at or below thethreshold for producingataxia.

Gabapentin also has been tested in a wide variety of animal models that are relevant foranalgesic actions.^[84] Generally, gabapentin is not active to prevent pain-related behaviors in models of acutenociceptive pain, but it prevents pain-related behaviors when animals are made sensitive by prior peripheralinflammation or peripheral nerve damage (inflammatory orneuropathic conditions).

Gabapentin is aligand of theα₂δ calcium channel subunit.^[85][86] The α₂δ-1 protein is coded by theCACNA2D1 gene. α₂δ was first described as an auxiliary protein connected to the main α₁ subunit (the channel-forming protein) of high voltage activatedvoltage-dependent calcium channels (L-type, N-type, P/Q type, and R-type).^[13] The same α₂δ protein has more recently been shown to interact directly with someNMDA-type andAMPA-typeglutamate receptors atpresynaptic sites and also withthrombospondin (anextracellular matrix protein secreted byastroglial cells).^[87]

Gabapentin is not a direct calciumchannel blocker: it exerts its actions by disrupting the regulatory function of α₂δ and its interactions with other proteins. Gabapentin reduces delivery of intracellular calcium channels to the cell membrane, reduces the activation of the channels by the α₂δ subunit, decreases signaling leading to neurotransmitters release, and disrupts interactions of α₂δ with voltage gated calcium channels but also withNMDA receptors,neurexins, andthrombospondin.^[13][14][15] These proteins are found as mutually interacting parts of the presynapticactive zone, where numerous protein molecules interact with each other to enable and to regulate the release ofneurotransmitters frompresynaptic vesicles into the synaptic space.^{[citation needed]}

Out of the four known isoforms of α₂δ protein, gabapentin binds with similar highaffinity to two:α₂δ-1 andα₂δ-2.^[86] All of the pharmacological properties of gabapentin tested to date are explained by its binding to just one isoform – α₂δ-1.^[86][14]

Theendogenousα-amino acidsL-leucine andL-isoleucine, which resemble gabapentin inchemical structure, bind α₂δ with similar affinity to gabapentin and are present in humancerebrospinal fluid at micromolar concentrations.^[88] They may be the endogenous ligands of the α₂δ subunit, and theycompetitively antagonize the effects of gabapentin.^[88][89] Accordingly, while gabapentin hasnanomolar affinity for the α₂δ subunit, its potencyin vivo is in the lowmicromolar range, and competition for binding by endogenousL-amino acids is likely to be responsible for this discrepancy.^[14]

Gabapentin is a potent activator of voltage-gated potassium channelsKCNQ3 andKCNQ5, even at low nanomolar concentrations. However, this activation is unlikely to be the dominant mechanism of gabapentin's therapeutic effects.^[90]

Gabapentin is structurally similar to the neurotransmitter glutamate and competitively inhibitsbranched-chain amino acid aminotransferase (BCAT), slowing down the synthesis of glutamate.^[91] In particular, it inhibits BCAT-1 at high concentrations (K_i = 1 mM), but not BCAT-2.^[92] At very high concentrations gabapentin can suppress the growth of cancer cells, presumably by affecting mitochondrial catabolism, however, the precise mechanism remains elusive.^[92]

Even though gabapentin is a structuralGABA analogue, and despite its name, it does not bind to theGABA receptors, does not convert intoGABATooltip γ-aminobutyric acid or anotherGABA receptor agonistin vivo, and does not modulate GABAtransport ormetabolism within the range of clinical dosing.^[85] In vitro gabapentin has been found to very weakly inhibit theGABA aminotransferase enzyme (K_i = 17–20 mM), however, this effect is so weak it is not clinically relevant at prescribed doses.^[91]

Gabapentin isabsorbed from theintestines by anactive transport process mediated via anamino acid transporter, presumably,LAT2.^[93] As a result, thepharmacokinetics of gabapentin is dose-dependent, with diminishedbioavailability and delayed peak levels at higher doses.^[86]

Theoral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule.^[7][94] Drugs that increase the transit time of gabapentin in thesmall intestine can increase its oral bioavailability; when gabapentin was co-administered with oralmorphine, the oral bioavailability of a 600 mg dose of gabapentin increased by 50%.^[94]

Gabapentin at a low dose of 100 mg has aT_max (time topeak levels) of approximately 1.7 hours, while the T_max increases to 3 to 4 hours at higher doses.^[86] Food does not significantly affect the T_max of gabapentin and increases the C_max andarea-under-curve levels of gabapentin by approximately 10%.^[94]

Gabapentin can cross theblood–brain barrier and enter thecentral nervous system.^[85] Gabapentin concentration incerebrospinal fluid is approximately 9–14% of itsblood plasma concentration.^[94] Due to its lowlipophilicity,^[94] gabapentin requires active transport across the blood–brain barrier.^{[95][85][96][97]} TheLAT1 is highly expressed at the blood–brain barrier^[98] and transports gabapentin across into thebrain.^{[95][85][96][97]} As with intestinal absorption mediated by an amino acid transporter, the transport of gabapentin across the blood–brain barrier by LAT1 is saturable.^[95] Gabapentin does not bind to other drug transporters such asP-glycoprotein (ABCB1) orOCTN2 (SLC22A5).^[95] It is not significantlybound to plasma proteins (<1%).^[94]

Gabapentin undergoes little or nometabolism.^[86][94]

Gabapentin is generally safe in people with livercirrhosis.^[99]

Gabapentin iseliminatedrenally in theurine.^[94] It has a relatively shortelimination half-life, with the reported average value of 5 to 7 hours.^[94] Because of its short elimination half-life, gabapentin must be administered 3 to 4 times per day to maintain therapeutic levels.^[100] Gabapentin XR (brand name Gralise) is taken once a day.^[101]

Gabapentin is a 3,3-disubstitutedderivative of GABA. Therefore, it is aGABA analogue, as well as aγ-amino acid.^[102][103] It is similar to several other compounds that collectively are calledgabapentinoids. Specifically, it is a derivative of GABA with a pentyl disubstitution at 3 position, hence, the name - gabapentin, in such a way as to form a six-membered ring. After the formation of the ring, theamine andcarboxylic groups are not in the same relative positions as they are in the GABA;^[104] they are moreconformationally constrained.^[105]

Although it has been known for some time that gabapentin must bind to the α₂δ-1 protein in order to act pharmacologically (see Pharmacodynamics), the three-dimensional structure of the α₂δ-1 protein with gabapentin bound (or alternatively, the native amino acid, L-Isoleucine bound) has only recently been obtained bycryo-electron microscopy.^[106] A figure of this drug-bound structure is shown in the Chemistry section of the entry ongabapentinoid drugs. This study confirms other findings to show that both compounds alternatively can bind at a single extracellular site (somewhat distant from the calcium conducting pore of thevoltage gated calcium channel α1 subunit) on the calcium channel and chemotaxis (Cache1) domain of α₂δ-1.

A process forchemical synthesis and isolation of gabapentin with high yield and purity^[107] starts with conversion of 1,1-cyclohexanediacetic anhydride to 1,1-cyclohexanediacetic acid monoamide and is followed by a 'Hofmann' rearrangement in an aqueous solution ofsodium hypobromite prepared in situ.

GABA is the principal inhibitoryneurotransmitter in mammalian brain. By the early 1970s, it was appreciated that there are two main classes ofGABA receptors,GABA_A andGABA_B and also thatbaclofen was anagonist of GABA_B receptors. Gabapentin was designed, synthesized and tested in mice by researchers at the pharmaceutical company Goedecke AG in Freiburg, Germany (a subsidiary ofParke-Davis). It was meant to be ananalogue of theneurotransmitter GABA that could more easily cross theblood–brain barrier. It was first synthesized in 1974/75 and described in 1975^[108] by Satzinger and Hartenstein.^[104][109]

The first pharmacology findings published were sedating properties and prevention ofseizures in mice evoked by theGABA antagonist,thiosemicarbazide.^[108] Shortly after, gabapentin was shown in vitro to reduce the release of the neurotransmitterdopamine from slices of ratcaudate nucleus (striatum).^[110] This study provided evidence that the action of gabapentin, unlike baclofen, did not arise from the GABA_B receptor.

Initialclinical trials utilizing small numbers of subjects were for treatment ofspasticity^[111] andmigraine^[112] but neither study had statistical power to allow conclusions. In 1987, the first positive results with gabapentin were obtained in a clinical trial using three dose groups versus pre-treatment seizure frequency for 75 days, as add-on treatment in patients who still had seizures despite taking other medications.^[113] This study did not show statistically significant results, but it did show a strong dose-related trend to decreased frequency of seizures.

Under the brand name Neurontin, it was first approved in the United Kingdom in May 1993, for the treatment of refractory epilepsy.^[114] Approval by theU.S. Food and Drug Administration followed in December 1993, also for use as an adjuvant (effective when added to other antiseizure drugs) medication to control partial seizures in adults; that indication was extended to children in 2000.^[115][7] Subsequently, gabapentin was approved in the United States for the treatment of pain frompostherpetic neuralgia in 2002.^[116] Ageneric version of gabapentin first became available in the United States in 2004.^[17] An extended-release formulation of gabapentin for once-daily administration, under the brand name Gralise, was approved in the United States for the treatment of postherpetic neuralgia in January 2011.^[117][118]

In recent years, gabapentin has been prescribed for an increasing range of disorders and is one of the more common medications used, particularly in elderly people.^[119]

Effective April 2019, the United Kingdom reclassified the drug as aclass C controlled substance.^{[120][121][122][123][124]}

Gabapentin is not a controlled substance under the federalControlled Substances Act.^[125] Effective 1 July 2017, Kentucky classified gabapentin as aschedule V controlled substance statewide.^[126] Gabapentin is scheduled V drug in other states such as West Virginia,^[127] Tennessee,^[128] Alabama,^[129] Utah,^[130] and Virginia.^[131]

Although some small, non-controlled studies in the 1990s—mostly sponsored by gabapentin's manufacturer—suggested that treatment for bipolar disorder with gabapentin may be promising,^[132] the preponderance of evidence suggests that it is not effective.^[133]

After the corporate acquisition of the original patent holder, the pharmaceutical company Pfizer admitted that there had been violations of FDA guidelines regarding the promotion of unproven off-label uses for gabapentin in theFranklin v. Parke-Davis case.

While off-label prescriptions are common for many drugs, marketing of off-label uses of a drug is not.^[20] In 2004,Warner-Lambert (which subsequently was acquired by Pfizer) agreed to plead guilty for activities of its Parke-Davis subsidiary, and to pay $430 million in fines to settle civil and criminal charges regarding the marketing of Neurontin for off-label purposes. The 2004 settlement wasone of the largest in U.S. history up to that point, and thefirst off-label promotion case brought successfully under the False Claims Act.^[134]

Kaiser Foundation Hospitals andKaiser Foundation Health Plan sued Pfizer Inc., alleging that the pharmaceutical company had misled Kaiser by recommending Neurontin as an off-label treatment for certain conditions (including bipolar disorder, migraines, andneuropathic pain).^{[135][136][137]} In 2010, a federal jury in Massachusetts ruled in Kaiser's favor, finding that Pfizer violated the federalRacketeer Influenced and Corrupt Organizations (RICO) Act and was liable forUS$47.36 million in damages, which wasautomatically trebled to just under $142.1 million.^[136][135]Aetna, Inc. and a group ofemployer health plans prevailed in their similar Neurontin-related claims against Pfizer.^[138] Pfizer appealed, but theU.S. Court of Appeals for the First Circuit upheld the verdict,^[138] and in 2013, theUS Supreme Court declined to hear the case.^[139][140]

Gabasync, a treatment consisting of a combination of gabapentin and two other medications (flumazenil andhydroxyzine) as well as therapy, is an ineffective treatment promoted formethamphetamine addiction, though it had also been claimed to be effective fordependence on alcohol orcocaine.^[141] It was marketed as PROMETA. While the individual drugs had been approved by the FDA, their off-label use for addiction treatment has not.^[142] Gabasync was marketed by Hythiam, Inc. which is owned byTerren Peizer, a formerjunk bond salesman who has since been convicted of securities fraud relative to another company.^{[143][144][145][141]} Hythiam charges up to $15,000 per patient to license its use (of which half goes to the prescribing physician, and half to Hythiam).^[146]

In a November 2005 article entitled "Curb Your Cravings For This Stock",Barrons wrote: "If the venture works out for patients and the investing public, it'll be a rare success for Peizer, who's promoted a series of disappointing small-cap medical or technology stocks ... since his days at Drexel".^[147]60 Minutes,NBC News, andThe Dallas Morning News criticized Peizer after the company bypassedclinical studies and government approval when bringing to market Prometa; the addiction drug proved to be completely ineffective.^{[148][149][141][150]}CBS News journalistScott Pelley said to Peizer in 2007: "Depending on who you talk to, you're either a revolutionary or asnake oil salesman."^[151][147] JournalistAdam Feuerstein opined: "most of what Peizer says is dubious-sounding hype".^[152]

In November 2011, the results of adouble-blind,placebo-controlled study (financed by Hythiam and carried out atUCLA) were published in thepeer-reviewed journalAddiction. It concluded that Gabasync is ineffective: "The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving."^[153]

The period from 2008 to 2018 saw a significant increase in the consumption of gabapentinoids. A study published in Nature Communications in 2023 highlights this trend, demonstrating a notable escalation in sales of gabapentinoids. The study, which analyzed healthcare data across 65 countries/ regions, found that the consumption rate of gabapentinoids had doubled over the decade, driven by their use in a wide range of indications.^[154]

Gabapentin was originally marketed under the brand name Neurontin. Since it became generic, it has been marketed worldwide using over 300 different brand names.^[1] Anextended-release formulation of gabapentin for once-daily administration was introduced in 2011, for postherpetic neuralgia under the brand name Gralise.^[155]

In the US, Neurontin is marketed byViatris afterUpjohn was spun off from Pfizer.^{[156][157][158]}

Parke-Davis developed a drug calledpregabalin, which is related in structure to gabapentin, as a successor to gabapentin.^[159] Another similar drugatagabalin has been unsuccessfully tried by Pfizer as a treatment for insomnia.^[160] Aprodrug form (gabapentin enacarbil)^[161] was approved by the U.S.Food and Drug Administration (FDA).

When taken in excess, gabapentin can induce euphoria, a sense of calm, improved sociability, and reduced alcohol or cocaine cravings.^{[162][163][164]} Also known on the streets as "Gabbies",^[165] gabapentin was reported in 2017 to be increasingly abused and misused for these euphoric effects.^[166][167] About 1 percent of the responders to an Internet poll and 22 percent of those attending addiction facilities had a history of abuse of gabapentin.^[79][168] Gabapentin misuse, toxicity, and use in suicide attempts among adults in the US increased from 2013 to 2017.^[169]

After Kentucky implemented stricter legislation regarding opioid prescriptions in 2012, there was an increase in gabapentin-only and multi-drug use from 2012 to 2015. The majority of these cases were from overdose in suspected suicide attempts. These rates were also accompanied by increases in abuse and recreational use.^[170]

Withdrawal symptoms, often resembling those ofbenzodiazepine withdrawal, play a role in the physical dependence some users experience.^[80] Its misuse predominantly coincides with the usage of otherCNS depressant drugs, namely opioids, benzodiazepines, and alcohol.^[171]

In cats, gabapentin can be used as an analgesic in multi-modal pain management,^[172] anxiety medication to reduce stress during travel or vet visits,^[173] and anticonvulsant.^[174]

Veterinarians may prescribe gabapentin as an anticonvulsant and pain reliever in dogs.^[175][174] It has beneficial effects for treatingepilepsy, different kinds of pain (chronic,neuropathic, and post-operative pain), and anxiety, lip-licking behaviour, storm phobia, fear-based aggression.^[176][177]

It is also used to treat chronic pain-associated nerve inflammation in horses and dogs. Side effects include tiredness and loss of coordination, but these effects generally go away within 24 hours of starting the medication.^[175][174]

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