View source for Gabapentin

{{Short description|Anticonvulsant medication}}
{{Use American English|date=September 2017}}
{{Use dmy dates|date=August 2024}}
{{Cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| verifiedrevid      = 461115603
| image              = Gabapentin2DACS.svg
| image_class        = skin-invert-image
| width              = 
| alt                = Gabapentin.acid
| image2             = Gabapentin3Dan.gif
| width2             = 
| alt2               = 
| caption            =

<!-- Clinical data -->
| pronounce          = 
| tradename          = Neurontin, others<ref name="Drugs.com"/>
| Drugs.com          = {{drugs.com|monograph|gabapentin}}
| MedlinePlus        = a694007
| DailyMedID         = Gabapentin
| pregnancy_AU       = B1
| pregnancy_AU_comment = <ref name="Drugs.com Pregnancy">{{cite web | title=Gabapentin Use During Pregnancy | website=Drugs.com | date=2 December 2019 | url=https://www.drugs.com/pregnancy/gabapentin.html | access-date=21 December 2019}}</ref>
| pregnancy_category = 
| dependency_liability = [[Physical dependence|Physical]]: High<ref name="Gabapentin withdrawal syndrome in t">{{cite journal | vauthors = Tran KT, Hranicky D, Lark T, Jacob NJ | title = Gabapentin withdrawal syndrome in the presence of a taper | journal = Bipolar Disorders | volume = 7 | issue = 3 | pages = 302–4 | date = June 2005 | pmid = 15898970 | doi = 10.1111/j.1399-5618.2005.00200.x }}</ref><br/>[[Psychological dependence|Psychological]]: Moderate
| addiction_liability = Low<ref name="Sch2014">{{cite journal | vauthors = Schifano F | title = Misuse and abuse of pregabalin and gabapentin: cause for concern? | journal = CNS Drugs | volume = 28 | issue = 6 | pages = 491–496 | date = June 2014 | pmid = 24760436 | doi = 10.1007/s40263-014-0164-4 | doi-access = free }}</ref>
| routes_of_administration = [[Oral administration|By mouth]]
| class              = [[Gabapentinoid]]
| ATC_prefix         = N02
| ATC_suffix         = BF01
| ATC_supplemental   =

<!-- Legal status -->
| legal_AU           = S4
| legal_AU_comment   = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_BR           = C1
| legal_BR_comment   = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA           = Rx-only
| legal_CA_comment   = 
| legal_DE           = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment   = 
| legal_NZ           = <!-- Class A, B, C -->
| legal_NZ_comment   = 
| legal_UK           = Class C
| legal_UK_comment   = 
| legal_US           = Rx-only, schedule 5 in select states
| legal_US_comment   = <ref name="Neurontin label" />
| legal_UN           = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment   = 
| legal_status       = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability    = 27–60% (inversely proportional to dose; a high-fat meal also increases bioavailability)<ref name=MSR>{{cite web |title = Neurontin, Gralise (gabapentin) dosing, indications, interactions, adverse effects, and more |work = Medscape Reference |publisher = WebMD |access-date = 6 April 2014 |url = http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall |url-status=live |archive-url = https://web.archive.org/web/20141216215811/http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall |archive-date = 16 December 2014 }}</ref><ref name = drugs93>{{cite journal | vauthors = Goa KL, Sorkin EM | title = Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy | journal = Drugs | volume = 46 | issue = 3 | pages = 409–427 | date = September 1993 | pmid = 7693432 | doi = 10.2165/00003495-199346030-00007 | s2cid = 265753780 }}</ref>
| protein_bound      = Less than 3%<ref name = MSR /><ref name = drugs93 />
| metabolism         = Not significantly metabolized<ref name = MSR /><ref name = drugs93 />
| metabolites        = 
| onset              = 
| elimination_half-life = 5 to 7 hours<ref name = MSR /><ref name = drugs93 />
| duration_of_action = 
| excretion          = [[Kidney]]<ref name = MSR /><ref name = drugs93 />

<!-- Identifiers -->
| CAS_number_Ref     = {{cascite|correct|CAS}}
| CAS_number         = 60142-96-3
| PubChem            = 3446
| IUPHAR_ligand      = 5483
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB00996
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 3328
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = 6CW7F3G59X
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00332
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 42797
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| ChEMBL             = 940
| NIAID_ChemDB       = 
| PDB_ligand         = GBN
| synonyms           = CI-945; GOE-3450; DM-1796 (Gralise)

<!-- Chemical and physical data -->
| IUPAC_name         = 2-[1-(Aminomethyl)cyclohexyl]acetic acid
| C                  = 9
| H                  = 17
| N                  = 1
| O                  = 2
| SMILES             = O=C(O)CC1(CN)CCCCC1
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12)
| StdInChI_comment   = 
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = UGJMXCAKCUNAIE-UHFFFAOYSA-N
| density            = 
| density_notes      = 
| melting_point      = 
| melting_high       = 
| melting_notes      = 
| boiling_point      = 
| boiling_notes      = 
| solubility         = 
| sol_units          = 
| specific_rotation  = 
}}

<!-- Definition and medical uses -->
'''Gabapentin''', sold under the brand name '''Neurontin''' among others, is an [[anticonvulsant]] medication primarily used to treat [[neuropathic pain]] and also for [[partial seizures]]<ref name="NICE"/><ref name="Neurontin label" /> of [[epilepsy]]. It is a commonly used medication for the treatment of neuropathic pain caused by [[diabetic neuropathy]], [[postherpetic neuralgia]], and [[central neuropathic pain|central pain]].<ref name=Attal2010>{{cite journal | vauthors = Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, Nurmikko T | title = EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision | journal = European Journal of Neurology | volume = 17 | issue = 9 | pages = 1113–1e88 | date = September 2010 | pmid = 20402746 | doi = 10.1111/j.1468-1331.2010.02999.x | s2cid = 14236933 | title-link = doi | doi-access = free }}</ref> It is moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit.<ref name=Wiffen2017 />

<!-- Side effects and mechanism -->
Gabapentin, like other [[gabapentinoid]] drugs, acts by decreasing activity of the [[CACNA2D1|α<sub>2</sub>δ-1 protein, coded by the CACNA2D1 gene]], first known as an auxiliary subunit of [[Voltage-gated calcium channel#α2δ Subunit|voltage gated calcium channels]].<ref name="pmid32521436" /><ref name="pmid23642658" /><ref name="pmid32321743" /> However, see Pharmacodynamics, below. By binding to α<sub>2</sub>δ-1, gabapentin reduces the release of excitatory [[neurotransmitter]]s (primarily [[Glutamic acid|glutamate]]) and as a result, reduces excess excitation of neuronal networks in the [[spinal cord]] and brain. Sleepiness and [[dizziness]] are the most common [[side effect]]s. Serious side effects include [[respiratory depression]], and [[allergy|allergic reactions]].<ref name="Neurontin label" /> As with all other antiepileptic drugs approved by the [[Food and Drug Administration|FDA]], gabapentin is labeled for an increased risk of [[suicide]]. Lower doses are recommended in those with [[kidney disease]].<ref name="Neurontin label" />

<!-- History, society and culture -->
Gabapentin was first approved for use in the United Kingdom in 1993.<ref>{{cite book | vauthors = Pitkänen A, Schwartzkroin PA, Moshé SL |title = Models of Seizures and Epilepsy |date = 2005 |publisher = Elsevier |location = Burlington |isbn = 978-0-08-045702-4 |page = 539 |url = https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539 |url-status=live |archive-url = https://web.archive.org/web/20170908192246/https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539 |archive-date = 8 September 2017 }}</ref> It has been available as a [[generic medication]] in the United States since 2004.<ref name="Reed2012"/> It is the first of several other drugs that are similar in structure and mechanism, called [[gabapentinoid]]s. In 2022, it was the tenth most commonly prescribed medication in the United States, with more than 40{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Gabapentin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Gabapentin | access-date = 30 August 2024 }}</ref> During the 1990s, [[Parke-Davis]], a subsidiary of [[Pfizer]], used a number of illegal techniques to encourage [[physician]]s in the United States to prescribe gabapentin for [[off-label|unapproved]] uses.<ref name=Hen2006>{{cite journal | vauthors = Henney JE | title = Safeguarding patient welfare: who's in charge? | journal = Annals of Internal Medicine | volume = 145 | issue = 4 | pages = 305–307 | date = August 2006 | pmid = 16908923 | doi = 10.7326/0003-4819-145-4-200608150-00013 | s2cid = 39262014 }}</ref> They have paid out millions of dollars to settle lawsuits regarding these activities.<ref>{{cite news | vauthors = Stempel J |title=Pfizer to pay $325 million in Neurontin settlement |url=https://www.reuters.com/article/us-pfizer-neurontin-settlement/pfizer-to-pay-325-million-in-neurontin-settlement-idUSKBN0ED1IS20140602 |access-date=11 June 2018 |work=Reuters |date=2 June 2014}}</ref>

{{TOC limit}}

==Medical uses==
Gabapentin is recommended for use in [[focal seizure]]s and [[neuropathic pain]].<ref name="Neurontin label" /><ref name="NICE">{{cite web |url=https://www.nice.org.uk/guidance/cg173/chapter/1-Recommendations |title=1 Recommendations &#124; Neuropathic pain in adults: pharmacological management in non-specialist settings &#124; Guidance |website=[[National Institute for Health and Care Excellence]] (NICE) |date=20 November 2013 |access-date=14 December 2020}}</ref> Gabapentin is prescribed [[off-label]] in the US and the UK,<ref name="pmid30480717">{{cite journal | vauthors = Montastruc F, Loo SY, Renoux C | title = Trends in First Gabapentin and Pregabalin Prescriptions in Primary Care in the United Kingdom, 1993-2017 | journal = JAMA | volume = 320 | issue = 20 | pages = 2149–2151 | date = November 2018 | pmid = 30480717 | pmc = 6583557 | doi = 10.1001/jama.2018.12358 | title-link = doi | doi-access = free }}</ref><ref name="pmid30907944">{{cite journal | vauthors = Goodman CW, Brett AS | title = A Clinical Overview of Off-label Use of Gabapentinoid Drugs | journal = JAMA Internal Medicine | volume = 179 | issue = 5 | pages = 695–701 | date = May 2019 | pmid = 30907944 | doi = 10.1001/jamainternmed.2019.0086 | s2cid = 85497732 }}</ref> for example, for the treatment of non-neuropathic pain,<ref name="pmid30480717"/> [[anxiety disorder]]s, sleep problems and [[bipolar disorder]].<ref name="Sobel2012">{{cite book | vauthors = Sobel SV |title = Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission |url = https://books.google.com/books?id=dnAlO_Veu2QC&pg=PA124 |date = 5 November 2012 |publisher = W. W. Norton |isbn = 978-0-393-70857-8 |page = 124 |url-status=live |archive-url = https://web.archive.org/web/20160106173227/https://books.google.com/books?id=dnAlO_Veu2QC&pg=PA124 |archive-date = 6 January 2016 }}</ref> In recent years, gabapentin has seen increased use, particularly in the elderly.<ref>{{Cite news | vauthors = Span P | date = 17 August 2024 | title = The Painkiller Used for Just About Anything |url=https://www.nytimes.com/2024/08/17/health/gabapentin-seniors-pain.html |access-date=28 Jan 2024 |work=The New York Times}}</ref> 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.<ref name="NIHR Evidence_2022" /><ref name="Hong_2022" /><ref name="Gabapentin withdrawal syndrome in t">{{cite journal | vauthors = Tran KT, Hranicky D, Lark T, Jacob NJ | title = Gabapentin withdrawal syndrome in the presence of a taper | journal = Bipolar Disorders | volume = 7 | issue = 3 | pages = 302–4 | date = June 2005 | pmid = 15898970 | doi = 10.1111/j.1399-5618.2005.00200.x }}</ref> 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.<ref>{{cite journal | vauthors = Mayo-Wilson E, Qureshi R, Hong H, Chen X, Li T | title = Harms were detected but not reported in six clinical trials of gabapentin | journal = Journal of Clinical Epidemiology | volume = 164 | pages = 76–87 | date = December 2023 | pmid = 37871835 | doi = 10.1016/j.jclinepi.2023.10.014 | url = https://osf.io/ej7fp }}</ref>

===Seizures===
Gabapentin is approved for the treatment of focal seizures;<ref>{{cite journal | vauthors = Johannessen SI, Ben-Menachem E | title = Management of focal-onset seizures: an update on drug treatment | journal = Drugs | volume = 66 | issue = 13 | pages = 1701–1725 | year = 2006 | pmid = 16978035 | doi = 10.2165/00003495-200666130-00004 | s2cid = 46952737 }}</ref> however, it is not effective for [[generalized epilepsy]].<ref name="pmid24798217">{{cite journal | vauthors = Rheims S, Ryvlin P | title = Pharmacotherapy for tonic-clonic seizures | journal = Expert Opinion on Pharmacotherapy | volume = 15 | issue = 10 | pages = 1417–1426 | date = July 2014 | pmid = 24798217 | doi = 10.1517/14656566.2014.915029 | s2cid = 6943460 }}</ref>

===Neuropathic pain===
Gabapentin is recommended as a first-line treatment for chronic neuropathic pain by various medical authorities.<ref name="NICE"/><ref name=Attal2010 /><ref name="pmid17372630">{{cite journal | vauthors = Moulin DE, Clark AJ, Gilron I, Ware MA, Watson CP, Sessle BJ, Coderre T, Morley-Forster PK, Stinson J, Boulanger A, Peng P, Finley GA, Taenzer P, Squire P, Dion D, Cholkan A, Gilani A, Gordon A, Henry J, Jovey R, Lynch M, Mailis-Gagnon A, Panju A, Rollman GB, Velly A | title = Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society | journal = Pain Research & Management | volume = 12 | issue = 1 | pages = 13–21 | date = 2007 | pmid = 17372630 | pmc = 2670721 | doi = 10.1155/2007/730785 | title-link = doi | doi-access = free }}</ref><ref name="pmid25575710">{{cite journal | vauthors = Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M | title = Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis | journal = The Lancet. Neurology | volume = 14 | issue = 2 | pages = 162–173 | date = February 2015 | pmid = 25575710 | pmc = 4493167 | doi = 10.1016/S1474-4422(14)70251-0 }}</ref> 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.<ref name=Attal2010 /><ref name="pmid25575710"/>

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]].<ref name=Wiffen2017>{{cite journal | vauthors = Wiffen PJ, Derry S, Bell RF, Rice AS, Tölle TR, Phillips T, Moore RA | title = Gabapentin for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD007938 | date = June 2017 | pmid = 28597471 | pmc = 6452908 | doi = 10.1002/14651858.CD007938.pub4 | hdl = 10044/1/52908 }}</ref> Gabapentin is approved for the former indication in the US.<ref name="Neurontin label" /> In addition to these two neuropathies, [[European Federation of Neurological Societies]] guideline notes gabapentin effectiveness for [[central pain]].<ref name=Attal2010 /> A combination of gabapentin with an [[opioid]] or [[nortriptyline]] may work better than either drug alone.<ref name=Attal2010 /><ref name="pmid25575710" />

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 with [[placebo]].<ref name=Wiffen2017/><!-- Not summarized in quite the same way in the cited source. -->

Evidence finds little or no benefit and significant risk in those with chronic [[low back pain]] or [[sciatica]].<ref name="Benefits and safety of gabapentinoi">{{cite journal | vauthors = Shanthanna H, Gilron I, Rajarathinam M, AlAmri R, Kamath S, Thabane L, Devereaux PJ, Bhandari M | title = Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials | journal = PLOS Medicine | volume = 14 | issue = 8 | pages = e1002369 | date = August 2017 | pmid = 28809936 | pmc = 5557428 | doi = 10.1371/journal.pmed.1002369 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Enke O, New HA, New CH, Mathieson S, McLachlan AJ, Latimer J, Maher CG, Lin CC | title = Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis | journal = CMAJ | volume = 190 | issue = 26 | pages = E786–E793 | date = July 2018 | pmid = 29970367 | pmc = 6028270 | doi = 10.1503/cmaj.171333 }}</ref> Gabapentin is not effective in [[HIV]]-associated [[Peripheral neuropathy|sensory neuropathy]]<ref>{{cite journal | vauthors = Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS | title = Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials | journal = PLOS ONE | volume = 5 | issue = 12 | pages = e14433 | date = December 2010 | pmid = 21203440 | pmc = 3010990 | doi = 10.1371/journal.pone.0014433 | title-link = doi | doi-access = free | bibcode = 2010PLoSO...514433P }}</ref> and neuropathic pain due to [[cancer]].<ref name="pmid29486015">{{cite journal | vauthors = Moore A, Derry S, Wiffen P | title = Gabapentin for Chronic Neuropathic Pain | journal = JAMA | volume = 319 | issue = 8 | pages = 818–819 | date = February 2018 | pmid = 29486015 | doi = 10.1001/jama.2017.21547 }}</ref>

===Anxiety===
There is a small amount of research on the use of gabapentin for the treatment of anxiety disorders.<ref name="pmid17502773">{{cite journal | vauthors = Mula M, Pini S, Cassano GB | title = The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence | journal = Journal of Clinical Psychopharmacology | volume = 27 | issue = 3 | pages = 263–272 | date = June 2007 | pmid = 17502773 | doi = 10.1097/jcp.0b013e318059361a | s2cid = 38188832 }}</ref><ref name="pmid29579375">{{cite journal | vauthors = Greenblatt HK, Greenblatt DJ | title = Gabapentin and Pregabalin for the Treatment of Anxiety Disorders | journal = Clinical Pharmacology in Drug Development | volume = 7 | issue = 3 | pages = 228–232 | date = March 2018 | pmid = 29579375 | doi = 10.1002/cpdd.446 | s2cid = 4321472 | doi-access = free }}</ref>

Gabapentin is effective for the long-term treatment of [[social anxiety disorder]] and in reducing [[Preoperational anxiety|preoperative anxiety]].<ref name="NIHR Evidence_2022">{{cite journal |date=17 October 2022 |title=Review finds little evidence to support gabapentinoid use in bipolar disorder or insomnia |url=https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_54173|s2cid=252983016 |url-access=subscription }}</ref><ref name="Hong_2022">{{cite journal | vauthors = Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, Harrison PJ, Cipriani A | title = Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale | journal = Molecular Psychiatry | volume = 27 | issue = 3 | pages = 1339–1349 | date = March 2022 | pmid = 34819636 | pmc = 9095464 | doi = 10.1038/s41380-021-01386-6 }}</ref>

In a controlled trial of breast cancer survivors with anxiety,<ref name="pmid29579375"/> and a trial for social phobia,<ref name="pmid17502773"/> gabapentin significantly reduced anxiety levels.

For [[panic disorder]], gabapentin has produced mixed results.<ref name="pmid29579375" /><ref name="pmid17502773" /><ref name="Hong_2022" />

===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 [[Medication discontinuation|discontinuation]] and [[Drug withdrawal|withdrawal symptoms]] after prolonged use at higher doses.<ref name="pmid28769860">{{cite journal | vauthors = Liu GJ, Karim MR, Xu LL, Wang SL, Yang C, Ding L, Wang YF | title = Efficacy and Tolerability of Gabapentin in Adults with Sleep Disturbance in Medical Illness: A Systematic Review and Meta-analysis | journal = Frontiers in Neurology | volume = 8 | pages = 316 | date = 2017 | pmid = 28769860 | pmc = 5510619 | doi = 10.3389/fneur.2017.00316 | title-link = doi | doi-access = free }}</ref>

Gabapentin enhances [[slow-wave sleep]] in people with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous [[arousal]].<ref name="pmid20124884">{{cite journal | vauthors = Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS | title = Treatment effects of gabapentin for primary insomnia | journal = Clinical Neuropharmacology | volume = 33 | issue = 2 | pages = 84–90 | date = 2010 | pmid = 20124884 | doi = 10.1097/WNF.0b013e3181cda242 | s2cid = 4046961 }}</ref>

===Drug dependence===
Gabapentin is moderately effective in reducing the symptoms of [[alcohol withdrawal]] and associated craving.<ref>{{cite journal | vauthors = Muncie HL, Yasinian Y, Oge' L | title = Outpatient management of alcohol withdrawal syndrome | journal = American Family Physician | volume = 88 | issue = 9 | pages = 589–595 | date = November 2013 | pmid = 24364635 }}</ref><ref name="Berlin_2015">{{cite journal | vauthors = Berlin RK, Butler PM, Perloff MD | title = Gabapentin Therapy in Psychiatric Disorders: A Systematic Review | journal = The Primary Care Companion for CNS Disorders | volume = 17 | issue = 5 | date = 2015 | pmid = 26835178 | pmc = 4732322 | doi = 10.4088/PCC.15r01821 }}</ref><ref name="pmid31461226">{{cite journal | vauthors = Ahmed S, Stanciu CN, Kotapati PV, Ahmed R, Bhivandkar S, Khan AM, Afridi A, Qureshi M, Esang M | title = Effectiveness of Gabapentin in Reducing Cravings and Withdrawal in Alcohol Use Disorder: A Meta-Analytic Review | journal = The Primary Care Companion for CNS Disorders | volume = 21 | issue = 4 | date = August 2019 | pmid = 31461226 | doi = 10.4088/PCC.19r02465 | s2cid = 201662179 }}</ref> 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.<ref name="pmid31077485">{{cite journal | vauthors = Kranzler HR, Feinn R, Morris P, Hartwell EE | title = A meta-analysis of the efficacy of gabapentin for treating alcohol use disorder | journal = Addiction | volume = 114 | issue = 9 | pages = 1547–1555 | date = September 2019 | pmid = 31077485 | pmc = 6682454 | doi = 10.1111/add.14655 }}</ref>

Gabapentin is ineffective in cocaine dependence and methamphetamine use,<ref name="pmid29241365">{{cite journal | vauthors = Mason BJ, Quello S, Shadan F | title = Gabapentin for the treatment of alcohol use disorder | journal = Expert Opinion on Investigational Drugs | volume = 27 | issue = 1 | pages = 113–124 | date = January 2018 | pmid = 29241365 | pmc = 5957503 | doi = 10.1080/13543784.2018.1417383 }}</ref> and it does not increase the rate of [[smoking cessation]].<ref>{{cite journal | vauthors = Sood A, Ebbert JO, Wyatt KD, Croghan IT, Schroeder DR, Sood R, Hays JT | title = Gabapentin for smoking cessation | journal = Nicotine & Tobacco Research | volume = 12 | issue = 3 | pages = 300–304 | date = March 2010 | pmid = 20081039 | pmc = 2825098 | doi = 10.1093/ntr/ntp195 }}</ref> While some studies indicate that gabapentin does not significantly reduce the symptoms of [[Opioid withdrawal|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]].<ref name="pmid24250527">{{cite journal | vauthors = Behnam B, Semnani V, Saghafi N, Ghorbani R, Dianak Shori M, Ghooshchian Choobmasjedi S | title = Gabapentin Effect on Pain Associated with Heroin Withdrawal in Iranian Crack: a Randomized Double-blind Clinical Trial | journal = Iranian Journal of Pharmaceutical Research | volume = 11 | issue = 3 | pages = 979–983 | date = 2012 | pmid = 24250527 | pmc = 3813133 }}</ref><ref name="pmid29241365"/> There is insufficient evidence for its use in [[Cannabis use disorder|cannabis dependence]].<ref>{{cite journal | vauthors = Nielsen S, Gowing L, Sabioni P, Le Foll B | title = Pharmacotherapies for cannabis dependence | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD008940 | date = January 2019 | pmid = 30687936 | pmc = 6360924 | doi = 10.1002/14651858.CD008940.pub3 }}</ref>

===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.<ref>{{cite journal | vauthors = McLean RJ, Gottlob I | title = The pharmacological treatment of nystagmus: a review | journal = Expert Opinion on Pharmacotherapy | volume = 10 | issue = 11 | pages = 1805–1816 | date = August 2009 | pmid = 19601699 | doi = 10.1517/14656560902978446 | s2cid = 21477128 }}</ref><ref name="pmid22072056">{{cite journal | vauthors = Thurtell MJ, Leigh RJ | title = Treatment of nystagmus | journal = Current Treatment Options in Neurology | volume = 14 | issue = 1 | pages = 60–72 | date = February 2012 | pmid = 22072056 | doi = 10.1007/s11940-011-0154-5 | s2cid = 40370476 }}</ref><ref name="pmid22661344">{{cite journal | vauthors = Mehta AR, Kennard C | title = The pharmacological treatment of acquired nystagmus | journal = Practical Neurology | volume = 12 | issue = 3 | pages = 147–153 | date = June 2012 | pmid = 22661344 | doi = 10.1136/practneurol-2011-000181 | s2cid = 1950738 }}</ref>

Gabapentin decreases the frequency of [[hot flash]]es in both menopausal women and people with breast cancer. However, antidepressants have similar efficacy, and treatment with [[estrogen]] more effectively prevents hot flashes.<ref name="pmid31870736">{{cite journal | vauthors = Shan D, Zou L, Liu X, Shen Y, Cai Y, Zhang J | title = Efficacy and safety of gabapentin and pregabalin in patients with vasomotor symptoms: a systematic review and meta-analysis | journal = American Journal of Obstetrics and Gynecology | volume = 222 | issue = 6 | pages = 564–579.e12 | date = June 2020 | pmid = 31870736 | doi = 10.1016/j.ajog.2019.12.011 | s2cid = 209462426 }}</ref>

Gabapentin reduces [[spasticity]] in [[multiple sclerosis]] and is prescribed as one of the first-line options.<ref name="pmid27207462">{{cite journal | vauthors = Otero-Romero S, Sastre-Garriga J, Comi G, Hartung HP, Soelberg Sørensen P, Thompson AJ, Vermersch P, Gold R, Montalban X | title = Pharmacological management of spasticity in multiple sclerosis: Systematic review and consensus paper | journal = Multiple Sclerosis | volume = 22 | issue = 11 | pages = 1386–1396 | date = October 2016 | pmid = 27207462 | doi = 10.1177/1352458516643600 | s2cid = 25028259 | url = https://discovery.ucl.ac.uk/id/eprint/1496196/ }}</ref> It is an established treatment of [[restless legs syndrome]].<ref name="pmid29756335">{{cite journal | vauthors = Winkelmann J, Allen RP, Högl B, Inoue Y, Oertel W, Salminen AV, Winkelman JW, Trenkwalder C, Sampaio C | title = Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)<sup>§</sup> | journal = Movement Disorders | volume = 33 | issue = 7 | pages = 1077–1091 | date = July 2018 | pmid = 29756335 | doi = 10.1002/mds.27260 | s2cid = 21669996 }}</ref> Gabapentin alleviates itching in kidney failure ([[uremic pruritus]])<ref>{{cite journal | vauthors = Berger TG, Steinhoff M | title = Pruritus and renal failure | journal = Seminars in Cutaneous Medicine and Surgery | volume = 30 | issue = 2 | pages = 99–100 | date = June 2011 | pmid = 21767770 | pmc = 3692272 | doi = 10.1016/j.sder.2011.04.005 | doi-broken-date = 1 November 2024 }}</ref><ref name="pmid33283264">{{cite journal | vauthors = Hercz D, Jiang SH, Webster AC | title = Interventions for itch in people with advanced chronic kidney disease | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 12 | pages = CD011393 | date = December 2020 | pmid = 33283264 | pmc = 8094883 | doi = 10.1002/14651858.CD011393.pub2 }}</ref> and itching of other causes.<ref>{{cite journal | vauthors = Anand S | title = Gabapentin for pruritus in palliative care | journal = The American Journal of Hospice & Palliative Care | volume = 30 | issue = 2 | pages = 192–196 | date = March 2013 | pmid = 22556282 | doi = 10.1177/1049909112445464 | s2cid = 39737885 }}</ref> It may be an option in [[essential tremor|essential]] or [[orthostatic tremor]].<ref>{{cite journal | vauthors = Schneider SA, Deuschl G | title = The treatment of tremor | journal = Neurotherapeutics | volume = 11 | issue = 1 | pages = 128–138 | date = January 2014 | pmid = 24142589 | pmc = 3899476 | doi = 10.1007/s13311-013-0230-5 }}</ref><ref>{{cite journal | vauthors = Zesiewicz TA, Elble RJ, Louis ED, Gronseth GS, Ondo WG, Dewey RB, Okun MS, Sullivan KL, Weiner WJ | title = Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology | journal = Neurology | volume = 77 | issue = 19 | pages = 1752–1755 | date = November 2011 | pmid = 22013182 | pmc = 3208950 | doi = 10.1212/WNL.0b013e318236f0fd }}</ref><ref>{{cite journal | vauthors = Sadeghi R, Ondo WG | title = Pharmacological management of essential tremor | journal = Drugs | volume = 70 | issue = 17 | pages = 2215–2228 | date = December 2010 | pmid = 21080739 | doi = 10.2165/11538180-000000000-00000 | s2cid = 10662268 }}</ref>

Gabapentin does not appear to provide benefit for [[bipolar disorder]],<ref name="Hong_2022" /><ref name="Berlin_2015"/><ref>{{cite journal | vauthors = Ng QX, Han MX, Teoh SE, Yaow CY, Lim YL, Chee KT | title = A Systematic Review of the Clinical Use of Gabapentin and Pregabalin in Bipolar Disorder | journal = Pharmaceuticals | volume = 14 | issue = 9 | pages = 834 | date = August 2021 | pmid = 34577534 | pmc = 8469561 | doi = 10.3390/ph14090834 | doi-access = free }}</ref> [[complex regional pain syndrome]],<ref>{{cite journal | vauthors = Tran DQ, Duong S, Bertini P, Finlayson RJ | title = Treatment of complex regional pain syndrome: a review of the evidence | journal = Canadian Journal of Anaesthesia | volume = 57 | issue = 2 | pages = 149–166 | date = February 2010 | pmid = 20054678 | doi = 10.1007/s12630-009-9237-0 | title-link = doi | doi-access = free }}</ref> post-surgical pain,<ref>{{cite journal | vauthors = Hamilton TW, Strickland LH, Pandit HG | title = A Meta-Analysis on the Use of Gabapentinoids for the Treatment of Acute Postoperative Pain Following Total Knee Arthroplasty | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 98 | issue = 16 | pages = 1340–1350 | date = August 2016 | pmid = 27535436 | doi = 10.2106/jbjs.15.01202 | url = https://ora.ox.ac.uk/objects/uuid:cbe29197-14a9-47dc-b961-2ad3e24fd1c0 | access-date = 22 August 2020 | url-status = dead | archive-url = https://web.archive.org/web/20200929012600/https://ora.ox.ac.uk/objects/uuid:cbe29197-14a9-47dc-b961-2ad3e24fd1c0 | archive-date = 29 September 2020 | url-access = subscription }}</ref> or [[tinnitus]],<ref>{{cite journal | vauthors = Aazh H, El Refaie A, Humphriss R | title = Gabapentin for tinnitus: a systematic review | journal = American Journal of Audiology | volume = 20 | issue = 2 | pages = 151–158 | date = December 2011 | pmid = 21940981 | doi = 10.1044/1059-0889(2011/10-0041) }}</ref> or prevent [[episodic migraine]] in adults.<ref>{{cite journal | vauthors = Linde M, Mulleners WM, Chronicle EP, McCrory DC | title = Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 6 | pages = CD010609 | date = June 2013 | pmid = 23797675 | pmc = 6599858 | doi = 10.1002/14651858.CD010609 }}</ref>

==Contraindications==
Gabapentin should be used carefully and at lower doses in people with [[Renal failure|kidney problems]] due to possible accumulation and toxicity. It is unclear if it is safe during [[pregnancy]] or [[breastfeeding]].<ref name="Neurontin label" />

==Side effects==
[[File:Gabapentin Orion bottle.jpg|thumb|upright|Gabapentin Orion 100 mg, bottle and pills in Sweden]]
[[Dizziness]] and [[somnolence]] are the most frequent [[side effect]]s.<ref name="Neurontin label" /> [[Fatigue (medical)|Fatigue]], [[ataxia]], [[peripheral edema]] (swelling of extremities), and [[nystagmus]] are also common.<ref name="Neurontin label" /> A 2017 meta-analysis found that gabapentin also increased the risk of difficulties in [[mentation]] and visual disturbances as compared to a placebo.<ref name="Benefits and safety of gabapentinoi"/> Gabapentin is associated with a weight gain of {{convert|2.2|kg|lb|abbr=on}} after 1.5 months of use.<ref name="pmid25590213">{{cite journal | vauthors = Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, Wang Z, Elraiyah T, Brito JP, Mauck KF, Lababidi MH, Prokop LJ, Asi N, Wei J, Fidahussein S, Montori VM, Murad MH | title = Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 2 | pages = 363–370 | date = February 2015 | pmid = 25590213 | pmc = 5393509 | doi = 10.1210/jc.2014-3421 }}</ref> Case studies indicate that it may cause [[anorgasmia]] and [[erectile dysfunction]],<ref name="pmid26559937">{{cite journal | vauthors = Yang Y, Wang X | title = Sexual dysfunction related to antiepileptic drugs in patients with epilepsy | journal = Expert Opinion on Drug Safety | volume = 15 | issue = 1 | pages = 31–42 | date = January 2016 | pmid = 26559937 | doi = 10.1517/14740338.2016.1112376 | s2cid = 39571068 }}</ref> as well as [[myoclonus]]<ref name="pmid29111014">{{cite journal | vauthors = Kim JB, Jung JM, Park MH, Lee EJ, Kwon DY | title = Negative myoclonus induced by gabapentin and pregabalin: A case series and systematic literature review | journal = Journal of the Neurological Sciences | volume = 382 | pages = 36–39 | date = November 2017 | pmid = 29111014 | doi = 10.1016/j.jns.2017.09.019 | s2cid = 32010921 }}</ref><ref name="pmid30381161">{{cite journal | vauthors = Desai A, Kherallah Y, Szabo C, Marawar R | title = Gabapentin or pregabalin induced myoclonus: A case series and literature review | journal = Journal of Clinical Neuroscience | volume = 61 | pages = 225–234 | date = March 2019 | pmid = 30381161 | doi = 10.1016/j.jocn.2018.09.019 | s2cid = 53165515 }}</ref> 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 [[pancreatitis|inflamed pancreas]], [[hallucination]]s, [[anaphylaxis]], [[respiratory depression]], and increased [[suicidal ideation]] are rare but serious side effects.<ref>{{cite web |title=Side effects of gabapentin|date=16 September 2021 |url=https://www.nhs.uk/medicines/gabapentin/side-effects-of-gabapentin/ |publisher=National Health Service |access-date=20 January 2024}}</ref>

===Suicide===
As with all antiepileptic drugs approved in the US, gabapentin label contains a warning of an increased risk of suicidal thoughts and behaviors.<ref name="Neurontin label">{{cite web | title=Neurontin- gabapentin capsule Neurontin- gabapentin tablet, film coated Neurontin- gabapentin solution | website=[[DailyMed]] | date=11 April 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee9ad9ed-6d9f-4ee1-9d7f-cfad438df388 | access-date=21 December 2019}}</ref> This warning is based on a meta-analysis of all approved antiepileptic drugs in 2008, and not with gabapentin alone.<ref name="Patorno_2010" /> According to an experimental meta-analysis of insurance claims database, gabapentin use is associated with about 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]].<ref name="Patorno_2010">{{cite journal | vauthors = Patorno E, Bohn RL, Wahl PM, Avorn J, Patrick AR, Liu J, Schneeweiss S | title = Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death | journal = JAMA | volume = 303 | issue = 14 | pages = 1401–1409 | date = April 2010 | pmid = 20388896 | doi = 10.1001/jama.2010.410 | title-link = doi | doi-access =  }}</ref> 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 (medication)|lithium]].<ref>{{cite journal | vauthors = Leith WM, Lambert WE, Boehnlein JK, Freeman MD | title = The association between gabapentin and suicidality in bipolar patients | journal = International Clinical Psychopharmacology | volume = 34 | issue = 1 | pages = 27–32 | date = January 2019 | pmid = 30383553 | doi = 10.1097/YIC.0000000000000242 | s2cid = 54130760 }}</ref> 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.<ref>{{cite journal | vauthors = Molero Y, Larsson H, D'Onofrio BM, Sharp DJ, Fazel S | title = Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden | journal = BMJ | volume = 365 | pages = l2147 | date = June 2019 | pmid = 31189556 | pmc = 6559335 | doi = 10.1136/bmj.l2147 }}</ref> 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.<ref>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</ref>

===Respiratory depression===
Serious breathing suppression, potentially fatal, may occur when gabapentin is taken together with [[opioid]]s, [[benzodiazepine]]s, or other [[depressant]]s, or by people with underlying lung problems such as [[COPD]].<ref name="FDA breathing">{{cite web | title=FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) | website=U.S. [[Food and Drug Administration]] (FDA) | date=19 December 2019 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin | archive-url=https://web.archive.org/web/20191222091828/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin | archive-date=22 December 2019 | url-status=dead | access-date=21 December 2019 }} {{PD-notice}}</ref> 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%.<ref name="FDA breathing" /> 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]].<ref>{{cite journal | vauthors = Rahman AA, Dell'Aniello S, Moodie EE, Durand M, Coulombe J, Boivin JF, Suissa S, Ernst P, Renoux C | title = Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study | journal = Annals of Internal Medicine | issue = Online ahead of print | date = January 2024 | volume = 177 | pages = 144–154 | pmid = 38224592 | doi = 10.7326/M23-0849 | s2cid = 266985259 }}</ref>

===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 effect|rebound]] phenomenon) {{emdash}} similar to, albeit less intense than most benzodiazepines.<ref name="pmid26721643">{{cite journal | vauthors = Mersfelder TL, Nichols WH | title = Gabapentin: Abuse, Dependence, and Withdrawal | journal = The Annals of Pharmacotherapy | volume = 50 | issue = 3 | pages = 229–233 | date = March 2016 | pmid = 26721643 | doi = 10.1177/1060028015620800 | s2cid = 21108959 }}</ref> Agitation, confusion and disorientation are the most frequently reported, followed by gastrointestinal complaints and sweating, and more rare [[tremor]], [[tachycardia]], [[hypertension]] and [[insomnia]].<ref name="pmid26721643" /> 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.<ref name="Bonnet_2017">{{cite journal | vauthors = Bonnet U, Scherbaum N | title = How addictive are gabapentin and pregabalin? A systematic review | journal = European Neuropsychopharmacology | volume = 27 | issue = 12 | pages = 1185–1215 | date = December 2017 | pmid = 28988943 | doi = 10.1016/j.euroneuro.2017.08.430 | s2cid = 10345555 }}</ref> All these symptoms subside when gabapentin is re-instated<ref name="pmid26721643" /> or [[Tapering (medicine)|tapered]] off gradually at an appropriate rate.{{Citation needed|date=May 2023}}

On its own, gabapentin appears to not have a substantial addictive power. In human and animal experiments, it shows limited to no [[rewarding]] effects. The vast majority of people abusing gabapentin are current or former abusers of opioids or sedatives.<ref name="Bonnet_2017" /> In these persons, gabapentin can boost the opioid "high" as well as decrease commonly experienced opioid-withdrawal symptoms such as anxiety.<ref>{{cite journal | vauthors = Bonnet U, Richter EL, Isbruch K, Scherbaum N | title = On the addictive power of gabapentinoids: a mini-review | journal = Psychiatria Danubina | volume = 30 | issue = 2 | pages = 142–149 | date = June 2018 | pmid = 29930223 | doi = 10.24869/psyd.2018.142 | s2cid = 49344251 | url = http://www.psychiatria-danubina.com/UserDocsImages/pdf/dnb_vol30_no2/dnb_vol30_no2_142.pdf }}</ref>

=== Psychiatric and behavioral adverse effects ===

Gabapentin is increasingly recognized to cause a range of psychiatric and behavioral adverse effects that extend beyond its more common neurological side effects. Systematic reviews have documented atypical manifestations such as [[aggression]], [[Agitation (medical)|agitation]], [[irritability]], mood instability, and [[suicidal ideation]], with some cases noting the emergence of [[mania]], [[hallucination]]s, and [[psychosis]], particularly in pediatric populations and individuals with preexisting psychiatric conditions.<ref name="Nwankwo_2024">{{cite journal | vauthors = Nwankwo A, Koyyalagunta D, Huh B, D'Souza RS, Javed S | title = A comprehensive review of the typical and atypical side effects of gabapentin | journal = Pain Practice| volume = 24 | issue = 8 | pages = 1051–1058 | date = November 2024 | pmid = 38949515 | doi = 10.1111/papr.13400 | url = }}</ref><ref name = "MC">{{cite web |title=Gabapentin (Oral Route) |url=https://www.mayoclinic.org/drugs-supplements/gabapentin-oral-route/description/drg-20064011 |work = Mayo Clinic |publisher=Mayo Foundation for Medical Education and Research |access-date=2025-06-01}}</ref><ref name = "Gál_2024">{{cite web | veditors = Patel A | vauthors = Gál K, Holland K | date = March 2024 |title=What are the side effects of gabapentin? |url=https://www.medicalnewstoday.com/articles/323753 | work = Medical News Today |publisher=Healthline Media |access-date=2025-06-01}}</ref>

Large [[cohort studies]] and post-marketing surveillance indicate that neuropsychiatric symptoms—including confusion, depression, and behavioral disturbances—can occur in up to 29% of gabapentin users, though most reactions are mild to moderate and often dose-dependent.<ref name="Huang_2023">{{cite journal | vauthors = Huang YH, Pan MH, Yang HI | title = The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan | journal = Frontiers in Pharmacology | volume = 14 | issue = | pages = 1128601 | date = 2023 | pmid = 37324474 | pmc = 10266423 | doi = 10.3389/fphar.2023.1128601 | doi-access = free | url = }}</ref> There is also evidence associating gabapentin with an increased risk of suicidal behavior, especially in younger patients, and rare reports of violent or aggressive behavior, though causality is difficult to establish and such events remain uncommon.<ref name="Molero_2019">{{cite journal | vauthors = Molero Y, Larsson H, D'Onofrio BM, Sharp DJ, Fazel S | title = Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden | journal = BMJ (Clinical Research Ed.) | volume = 365 | issue = | pages = l2147 | date = June 2019 | pmid = 31189556 | pmc = 6559335 | doi = 10.1136/bmj.l2147 | url = }}</ref><ref name="Athavale_2023">{{cite journal | vauthors = Athavale A, Murnion B | title = Gabapentinoids: a therapeutic review | journal = Australian Prescriber | volume = 46 | issue = 4 | pages = 80–85 | date = December 2023 | pmid = 38152314 | pmc = 10751078 | doi = 10.18773/austprescr.2023.025 | url = }}</ref>

==Overdose==
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 with [[alcohol (drug)|alcohol]] or [[opioid]]s.<ref name="Bonnet_2017" /><ref>R.C. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 677–8. {{ISBN|978-0-9626523-7-0}}.</ref>

==Pharmacology==

=== Animal Models ===
Gabapentin, prevents [[seizure]]s in a [[Dose–response relationship|dose]]-related manner in several laboratory [[animal models]].<ref>{{cite journal | vauthors = Vartanian MG, Radulovic LL, Kinsora JJ, Serpa KA, Vergnes M, Bertram E, Taylor CP | title = Activity profile of pregabalin in rodent models of epilepsy and ataxia | journal = Epilepsy Research | volume = 68 | issue = 3 | pages = 189–205 | date = March 2006 | pmid = 16337109 | doi = 10.1016/j.eplepsyres.2005.11.001 }}</ref> These models include spinal extensor seizures from low-intensity electroshock to the [[forebrain]] 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 "[[Kindling model of epilepsy|kindled]]" to produce [[focal seizure]]s by repeated prior electrical stimulation of the [[hippocampus]]. Gabapentin slightly increased spontaneous [[Absence seizure|absence]]-like seizures in a genetically susceptible strain recorded with [[electroencephalography]]. All of these effects of gabapentin were seen at dosages at or below the [[Threshold dose|threshold]] for producing [[ataxia]].

Gabapentin also has been tested in a wide variety of animal models that are relevant for [[analgesic]] actions.<ref>{{cite journal | vauthors = Cheng JK, Chiou LC | title = Mechanisms of the antinociceptive action of gabapentin | journal = Journal of Pharmacological Sciences | volume = 100 | issue = 5 | pages = 471–486 | date = 2006 | pmid = 16474201 | doi = 10.1254/jphs.CR0050020 }}</ref> Generally, gabapentin is not active to prevent pain-related behaviors in models of acute [[Nociceptive pain|nociceptive]] pain, but it prevents pain-related behaviors when animals are made sensitive by prior peripheral [[inflammation]] or peripheral nerve damage (inflammatory or [[Peripheral neuropathy|neuropathic]] conditions).

===Pharmacodynamics===
Gabapentin is a [[ligand (biochemistry)|ligand]] of the [[Voltage-dependent calcium channel#.CE.B12.CE.B4 Subunit|α<sub>2</sub>δ calcium channel subunit]].<ref name="pmid16376147">{{cite journal | vauthors = Sills GJ | title = The mechanisms of action of gabapentin and pregabalin | journal = Current Opinion in Pharmacology | volume = 6 | issue = 1 | pages = 108–113 | date = February 2006 | pmid = 16376147 | doi = 10.1016/j.coph.2005.11.003 }}</ref><ref name="pmid27345098">{{cite journal | vauthors = Calandre EP, Rico-Villademoros F, Slim M | title = Alpha<sub>2</sub>delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use | journal = Expert Review of Neurotherapeutics | volume = 16 | issue = 11 | pages = 1263–1277 | date = November 2016 | pmid = 27345098 | doi = 10.1080/14737175.2016.1202764 | s2cid = 33200190 }}</ref> The α<sub>2</sub>δ-1 protein is coded by the [[CACNA2D1]] gene. α<sub>2</sub>δ was first described as an auxiliary protein connected to the main α<sub>1</sub> subunit (the channel-forming protein) of high voltage activated [[voltage-dependent calcium channel]]s (L-type, N-type, P/Q type, and R-type).<ref name="pmid32521436">{{cite journal | vauthors = Risher WC, Eroglu C | title = Emerging roles for α2δ subunits in calcium channel function and synaptic connectivity | journal = Current Opinion in Neurobiology | volume = 63 | pages = 162–169 | date = August 2020 | pmid = 32521436 | pmc = 7483897 | doi = 10.1016/j.conb.2020.04.007 }}</ref> The same α<sub>2</sub>δ protein has more recently been shown to interact directly with some [[NMDA receptor|NMDA-type]] and [[AMPA receptor|AMPA-type]] [[Glutamic acid|glutamate]] receptors at [[presynaptic]] sites and also with [[thrombospondin]] (an [[extracellular matrix]] protein secreted by [[Astrocyte|astroglial cells]]).<ref>{{cite journal | vauthors = Taylor CP, Harris EW | title = Analgesia with Gabapentin and Pregabalin May Involve ''N''-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 374 | issue = 1 | pages = 161–174 | date = July 2020 | pmid = 32321743 | doi = 10.1124/jpet.120.266056 }}</ref>

Gabapentin is not a direct calcium [[channel blocker]]: it exerts its actions by disrupting the regulatory function of α<sub>2</sub>δ 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 α<sub>2</sub>δ subunit, decreases signaling leading to neurotransmitters release, and disrupts interactions of α<sub>2</sub>δ with voltage gated calcium channels but also with [[NMDA receptor]]s, [[neurexin]]s, and [[thrombospondin]].<ref name="pmid32521436" /><ref name="pmid23642658">{{cite journal | vauthors = Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A | title = The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities? | journal = Trends in Pharmacological Sciences | volume = 34 | issue = 6 | pages = 332–339 | date = June 2013 | pmid = 23642658 | doi = 10.1016/j.tips.2013.04.001 }}</ref><ref name="pmid32321743">{{cite journal | vauthors = Taylor CP, Harris EW | title = Analgesia with Gabapentin and Pregabalin May Involve ''N''-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 374 | issue = 1 | pages = 161–174 | date = July 2020 | pmid = 32321743 | doi = 10.1124/jpet.120.266056 | s2cid = 216082872 | title-link = doi | doi-access = free }}</ref> These proteins are found as mutually interacting parts of the presynaptic [[active zone]], where numerous protein molecules interact with each other to enable and to regulate the release of [[neurotransmitter]]s from [[Synaptic vesicle|presynaptic vesicles]] into the synaptic space.{{citation needed|date=February 2025}}

Out of the four known isoforms of α<sub>2</sub>δ protein, gabapentin binds with similar high [[affinity (pharmacology)|affinity]] to two: [[CACNA2D1|α<sub>2</sub>δ-1]] and [[CACNA2D2|α<sub>2</sub>δ-2]].<ref name="pmid27345098" /> All of the pharmacological properties of gabapentin tested to date are explained by its binding to just one isoform – α<sub>2</sub>δ-1.<ref name="pmid27345098" /><ref name="pmid23642658" />

The [[endogenous]] [[α-amino acid]]s [[L-leucine|<small>L</small>-leucine]] and [[L-isoleucine|<small>L</small>-isoleucine]], which resemble gabapentin in [[chemical structure]], bind α<sub>2</sub>δ with similar affinity to gabapentin and are present in human [[cerebrospinal fluid]] at micromolar concentrations.<ref name="pmid17222465">{{cite journal | vauthors = Dooley DJ, Taylor CP, Donevan S, Feltner D | title = Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission | journal = Trends in Pharmacological Sciences | volume = 28 | issue = 2 | pages = 75–82 | date = February 2007 | pmid = 17222465 | doi = 10.1016/j.tips.2006.12.006 }}</ref> They may be the endogenous ligands of the α<sub>2</sub>δ subunit, and they [[competitive inhibition|competitively antagonize]] the effects of gabapentin.<ref name="pmid17222465" /><ref name="pmid17403543">{{cite journal | vauthors = Davies A, Hendrich J, Van Minh AT, Wratten J, Douglas L, Dolphin AC | title = Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels | journal = Trends in Pharmacological Sciences | volume = 28 | issue = 5 | pages = 220–228 | date = May 2007 | pmid = 17403543 | doi = 10.1016/j.tips.2007.03.005 }}</ref> Accordingly, while gabapentin has [[nanomolar]] affinity for the α<sub>2</sub>δ subunit, its potency ''in vivo'' is in the low [[micromolar]] range, and competition for binding by endogenous <small>L</small>-amino acids is likely to be responsible for this discrepancy.<ref name="pmid23642658"/>

Gabapentin is a potent activator of voltage-gated potassium channels [[KCNQ3]] and [[KCNQ5]], even at low nanomolar concentrations. However, this activation is unlikely to be the dominant mechanism of gabapentin's therapeutic effects.<ref name="pmid30021858">{{cite journal | vauthors = Manville RW, Abbott GW | title = Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels | journal = Molecular Pharmacology | volume = 94 | issue = 4 | pages = 1155–1163 | date = October 2018 | pmid = 30021858 | pmc = 6108572 | doi = 10.1124/mol.118.112953 }}</ref>

Gabapentin is structurally similar to the neurotransmitter glutamate and competitively inhibits [[branched-chain amino acid aminotransferase]] (BCAT), slowing down the synthesis of glutamate.<ref name="inhibition">{{cite journal | vauthors = Goldlust A, Su TZ, Welty DF, Taylor CP, Oxender DL | title = Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA | journal = Epilepsy Research | volume = 22 | issue = 1 | pages = 1–11 | date = September 1995 | pmid = 8565962 | doi = 10.1016/0920-1211(95)00028-9 }}</ref> In particular, it inhibits BCAT-1 at high concentrations (K<sub>i</sub> = 1&nbsp;mM), but not BCAT-2.<ref name="BCAT">{{cite journal | vauthors = Grankvist N, Lagerborg KA, Jain M, Nilsson R | title = Gabapentin Can Suppress Cell Proliferation Independent of the Cytosolic Branched-Chain Amino Acid Transferase 1 (BCAT1) | journal = Biochemistry | volume = 57 | issue = 49 | pages = 6762–6766 | date = December 2018 | pmid = 30427175 | doi = 10.1021/acs.biochem.8b01031 | pmc = 6528808 }}</ref> At very high concentrations gabapentin can suppress the growth of cancer cells, presumably by affecting mitochondrial catabolism, however, the precise mechanism remains elusive.<ref name="BCAT"/>

Even though gabapentin is a structural [[GABA analogue]], and despite its name, it does not bind to the [[GABA receptor]]s, does not convert into {{abbrlink|GABA|γ-aminobutyric acid}} or another [[GABA receptor agonist]] ''[[in vivo]]'', and does not modulate GABA [[neurotransmitter transport|transport]] or [[metabolism]] within the range of clinical dosing.<ref name="pmid16376147" /> In vitro gabapentin has been found to very weakly inhibit the [[GABA aminotransferase]] enzyme (K<sub>i</sub> = 17–20&nbsp;mM), however, this effect is so weak it is not clinically relevant at prescribed doses.<ref name="inhibition"/>

===Pharmacokinetics===
Gabapentin is [[Absorption (pharmacology)|absorbed]] from the [[intestine]]s by an [[active transport]] process mediated via an [[Heterodimeric amino-acid transporter|amino acid transporter]], presumably, [[SLC7A8|LAT2]].<ref name="pmid18656534">{{cite journal | vauthors = del Amo EM, Urtti A, Yliperttula M | title = Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2 | journal = European Journal of Pharmaceutical Sciences | volume = 35 | issue = 3 | pages = 161–174 | date = October 2008 | pmid = 18656534 | doi = 10.1016/j.ejps.2008.06.015 }}</ref> As a result, the [[pharmacokinetics]] of gabapentin is dose-dependent, with diminished [[bioavailability]] and delayed peak levels at higher doses.<ref name="pmid27345098" />

The [[oral administration|oral]] bioavailability of gabapentin is approximately 80% at 100&nbsp;mg administered three times daily once every 8&nbsp;hours, but decreases to 60% at 300&nbsp;mg, 47% at 400&nbsp;mg, 34% at 800&nbsp;mg, 33% at 1,200&nbsp;mg, and 27% at 1,600&nbsp;mg, all with the same dosing schedule.<ref name="Neurontin label" /><ref name="pmid20818832">{{cite journal | vauthors = Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P | title = A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin | journal = Clinical Pharmacokinetics | volume = 49 | issue = 10 | pages = 661–669 | date = October 2010 | pmid = 20818832 | doi = 10.2165/11536200-000000000-00000 | s2cid = 16398062 }}</ref> Drugs that increase the transit time of gabapentin in the [[small intestine]] can increase its oral bioavailability; when gabapentin was co-administered with oral [[morphine]], the oral bioavailability of a 600&nbsp;mg dose of gabapentin increased by 50%.<ref name="pmid20818832" />

Gabapentin at a low dose of 100&nbsp;mg has a [[Tmax (pharmacology)|T<sub>max</sub>]] (time to [[Cmax (pharmacology)|peak levels]]) of approximately 1.7&nbsp;hours, while the T<sub>max</sub> increases to 3 to 4&nbsp;hours at higher doses.<ref name="pmid27345098" /> Food does not significantly affect the T<sub>max</sub> of gabapentin and increases the C<sub>max</sub> and [[area-under-curve (pharmacokinetics)|area-under-curve level]]s of gabapentin by approximately 10%.<ref name="pmid20818832" />

Gabapentin can cross the [[blood–brain barrier]] and enter the [[central nervous system]].<ref name="pmid16376147" /> Gabapentin concentration in [[cerebrospinal fluid]] is approximately 9–14% of its [[blood plasma]] concentration.<ref name="pmid20818832"/> Due to its low [[lipophilicity]],<ref name="pmid20818832" /> gabapentin requires active transport across the blood–brain barrier.<ref name="pmid23567998">{{cite journal | vauthors = Dickens D, Webb SD, Antonyuk S, Giannoudis A, Owen A, Rädisch S, Hasnain SS, Pirmohamed M | title = Transport of gabapentin by LAT1 (SLC7A5) | journal = Biochemical Pharmacology | volume = 85 | issue = 11 | pages = 1672–1683 | date = June 2013 | pmid = 23567998 | doi = 10.1016/j.bcp.2013.03.022 }}</ref><ref name="pmid16376147" /><ref name="pmid26305616">{{cite journal | vauthors = Geldenhuys WJ, Mohammad AS, Adkins CE, Lockman PR | title = Molecular determinants of blood-brain barrier permeation | journal = Therapeutic Delivery | volume = 6 | issue = 8 | pages = 961–971 | year = 2015 | pmid = 26305616 | pmc = 4675962 | doi = 10.4155/tde.15.32 }}</ref><ref name="pmid19937841">{{cite journal | vauthors = Müller CE | title = Prodrug approaches for enhancing the bioavailability of drugs with low solubility | journal = Chemistry & Biodiversity | volume = 6 | issue = 11 | pages = 2071–2083 | date = November 2009 | pmid = 19937841 | doi = 10.1002/cbdv.200900114 | s2cid = 32513471 }}</ref> The [[SLC7A5|LAT1]] is highly expressed at the blood–brain barrier<ref name="pmid10518579">{{cite journal | vauthors = Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM | title = Selective expression of the large neutral amino acid transporter at the blood-brain barrier | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 21 | pages = 12079–12084 | date = October 1999 | pmid = 10518579 | pmc = 18415 | doi = 10.1073/pnas.96.21.12079 | title-link = doi | doi-access = free | bibcode = 1999PNAS...9612079B }}</ref> and transports gabapentin across into the [[brain]].<ref name="pmid23567998" /><ref name="pmid16376147" /><ref name="pmid26305616" /><ref name="pmid19937841" /> As with intestinal absorption mediated by an amino acid transporter, the transport of gabapentin across the blood–brain barrier by LAT1 is saturable.<ref name="pmid23567998" /> Gabapentin does not bind to other drug transporters such as [[P-glycoprotein]] (ABCB1) or [[OCTN2]] (SLC22A5).<ref name="pmid23567998" /> It is not significantly [[plasma protein binding|bound to plasma protein]]s (<1%).<ref name="pmid20818832" />

Gabapentin undergoes little or no [[metabolism]].<ref name="pmid27345098" /><ref name="pmid20818832" />

Gabapentin is generally safe in people with liver [[cirrhosis]].<ref name="pmid37918778">{{cite journal |vauthors=Ma J, Björnsson ES, Chalasani N |title=The Safe Use of Analgesics in Patients with Cirrhosis: A Narrative Review |journal=Am J Med |volume=137 |issue=2 |pages=99–106 |date=February 2024 |pmid=37918778 |doi=10.1016/j.amjmed.2023.10.022|s2cid=264888110 }}</ref>

Gabapentin is [[elimination (pharmacology)|eliminated]] [[renal]]ly in the [[urine]].<ref name="pmid20818832" /> It has a relatively short [[elimination half-life]], with the reported average value of 5 to 7&nbsp;hours.<ref name="pmid20818832" /> Because of its short elimination half-life, gabapentin must be administered 3 to 4&nbsp;times per day to maintain therapeutic levels.<ref name="pmid20505847">{{cite journal | vauthors = Agarwal P, Griffith A, Costantino HR, Vaish N | title = Gabapentin enacarbil - clinical efficacy in restless legs syndrome | journal = Neuropsychiatric Disease and Treatment | volume = 6 | pages = 151–158 | date = May 2010 | pmid = 20505847 | pmc = 2874339 | doi = 10.2147/NDT.S5712 | doi-access = free }}</ref> Gabapentin XR (brand name Gralise) is taken once a day.<ref name="Kaye2017">{{cite book | vauthors = Kaye AD |title=Pharmacology, An Issue of Anesthesiology Clinics E-Book|url=https://books.google.com/books?id=lsUmDwAAQBAJ&pg=PT98|date=5 June 2017|publisher=Elsevier Health Sciences|isbn=978-0-323-52998-3|pages=98–}}</ref>

==Chemistry==
[[File:gaba and gabapentin.png|class=skin-invert-image|thumb|right|300px|Chemical structures of GABA and gabapentin, with commonalities highlighted]]

Gabapentin is a 3,3-di[[substituent|substituted]] [[chemical derivative|derivative]] of GABA. Therefore, it is a [[GABA analogue]], as well as a [[amino acid|γ-amino acid]].<ref name="WyllieCascino2012">{{cite book | vauthors = Wyllie E, Cascino GD, Gidal BE, Goodkin HP | title = Wyllie's Treatment of Epilepsy: Principles and Practice | url = https://books.google.com/books?id=j9t6Qg0kkuUC&pg=RA1-PA423 | date = 17 February 2012 | publisher = Lippincott Williams & Wilkins | isbn = 978-1-4511-5348-4 | page = 423}}</ref><ref name="BenzonRathmell2013">{{cite book | vauthors = Benzon H, Rathmell JP, Wu CL, Turk DC, Argoff CE, Hurley RW | title = Practical Management of Pain | url = https://books.google.com/books?id=kfcDAQAAQBAJ&pg=PA1006 | date = 11 September 2013 | publisher = Elsevier Health Sciences | isbn = 978-0-323-17080-2 | page = 1006}}</ref> It is similar to several other compounds that collectively are called [[gabapentinoid]]s. Specifically, it is a derivative of GABA with a pentyl disubstitution at 3 position, hence, the name - gaba''pentin'', in such a way as to form a six-membered ring. After the formation of the ring, the [[amine]] and [[carboxylic]] groups are not in the same relative positions as they are in the GABA;<ref name="Sneader2005">{{cite book | vauthors = Sneader W |title = Drug Discovery: A History |date = 2005 |publisher = John Wiley & Sons |isbn = 978-0-470-01552-0 |pages = 219–220 |url = https://books.google.com/books?id=jglFsz5EJR8C&pg=PA219}}</ref> they are more [[conformation–activity relationship|conformationally]] constrained.<ref name="pmid21428817">{{cite journal | vauthors = Levandovskiy IA, Sharapa DI, Shamota TV, Rodionov VN, Shubina TE | title = Conformationally restricted GABA analogs: from rigid carbocycles to cage hydrocarbons | journal = Future Medicinal Chemistry | volume = 3 | issue = 2 | pages = 223–241 | date = February 2011 | pmid = 21428817 | doi = 10.4155/fmc.10.287 }}</ref>

Although it has been known for some time that gabapentin must bind to the α<sub>2</sub>δ-1 protein in order to act pharmacologically (see Pharmacodynamics), the three-dimensional structure of the α<sub>2</sub>δ-1 protein with gabapentin bound (or alternatively, the native amino acid, L-Isoleucine bound) has only recently been obtained by [[Cryogenic electron microscopy|cryo-electron microscopy]].<ref>{{cite journal | vauthors = Chen Z, Mondal A, Minor DL | title = Structural basis for Ca<sub>V</sub>α<sub>2</sub>δ:gabapentin binding | journal = Nature Structural & Molecular Biology | volume = 30 | issue = 6 | pages = 735–739 | date = June 2023 | pmid = 36973510 | pmc = 10896480 | doi = 10.1038/s41594-023-00951-7 }}</ref> A figure of this drug-bound structure is shown in the Chemistry section of the entry on [[gabapentinoid]] 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 the [[Voltage-gated calcium channel|voltage gated calcium channel]] α1 subunit) on the calcium channel and chemotaxis ([[Cache domain|Cache]]1) domain of α<sub>2</sub>δ-1.

===Synthesis===
[[File:synthesis of gabapentin.png|class=skin-invert-image|thumb|right|500px|Synthesis of gabapentin.]]

A process for [[chemical synthesis]] and isolation of gabapentin with high yield and purity<ref>{{cite web | vauthors = Kumar A, Soudagar SR, Nijasure AM, Panda NB, Gautam P, Thakur GR |title=Process For Synthesis Of Gabapentin |url=https://patents.google.com/patent/US20080103334A1/en }}</ref> 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 of [[sodium hypobromite]] prepared in situ.

==History==
[[GABA]] is the principal inhibitory [[neurotransmitter]] in mammalian brain. By the early 1970s, it was appreciated that there are two main classes of [[GABA receptor]]s, [[GABAA receptor|GABA<sub>A</sub>]] and [[GABAB receptor|GABA<sub>B</sub>]] and also that [[baclofen]] was an  [[agonist]] of GABA<sub>B</sub> receptors. Gabapentin was designed, synthesized and tested in mice by researchers at the pharmaceutical company Goedecke AG in Freiburg, Germany (a subsidiary of [[Parke-Davis]]). It was meant to be an [[structural analog|analogue]] of the [[neurotransmitter]] GABA that could more easily cross the [[blood–brain barrier]]. It was first synthesized in 1974/75 and described in 1975<ref name="US4024175">{{Cite patent|number=US4024175A|title=Cyclic amino acids|gdate=1977-05-17|inventor = Satzinger G, Hartenstein J, Herrmann M, Heldt W |url=https://patents.google.com/patent/US4024175A/en}}</ref> by Satzinger and Hartenstein.<ref name="Sneader2005" /><ref name="JohnsonLi2013">{{cite book | vauthors = Johnson DS, Li JJ |title=The Art of Drug Synthesis|url=https://books.google.com/books?id=zvruBDAulWEC&pg=SA13-PA41|date=26 February 2013|publisher=John Wiley & Sons|isbn=978-1-118-67846-6|pages=13–}}</ref>

The first pharmacology findings published were sedating properties and prevention of [[Epilepsy|seizures]] in mice evoked by the [[GABA receptor antagonist|GABA antagonist]], [[thiosemicarbazide]].<ref name="US4024175" /> Shortly after, gabapentin was shown in vitro to reduce the release of the neurotransmitter [[dopamine]] from slices of rat [[caudate nucleus]] (striatum).<ref>{{cite journal | vauthors = Reimann W | title = Inhibition by GABA, baclofen and gabapentin of dopamine release from rabbit caudate nucleus: are there common or different sites of action? | journal = European Journal of Pharmacology | volume = 94 | issue = 3–4 | pages = 341–344 | date = October 1983 | pmid = 6653664 | doi = 10.1016/0014-2999(83)90425-9 }}</ref> This study provided evidence that the action of gabapentin, unlike baclofen, did not arise from the GABA<sub>B</sub> receptor.

Initial [[clinical trial]]s utilizing small numbers of subjects were for treatment of [[spasticity]]<ref>{{Cite journal | vauthors = Prevo AJ, Slootman HJ, Harlaar J, Vogelaar TW |date=1985 |title=A new antispastic agent: gabapentin: its effect on EMG analysis during voluntary movement in hemiplegia |url=https://www.sciencedirect.com/journal/electroencephalography-and-clinical-neurophysiology |journal=Clinical Neurophysiology |volume=62 |issue=3 |pages=S221|doi=10.1016/0013-4694(85)90838-7 |url-access=subscription }}</ref> and [[migraine]]<ref>{{Cite journal | vauthors = Wessely P, Baumgartner C, Klingler D, Kreczi J, Meyerson N, Sailer L, Saltuari L, Schütt P |date=1987 |title=Preliminary Results Of A Double Blind Study With The New Migraine Prophylactic Drug Gabapentin |journal=Cephalalgia |language=en |volume=7 |issue=6_suppl |pages=477–478 |doi=10.1177/03331024870070S6214 |issn=0333-1024}}</ref> 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.<ref>{{cite journal | vauthors = Crawford P, Ghadiali E, Lane R, Blumhardt L, Chadwick D | title = Gabapentin as an antiepileptic drug in man | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 50 | issue = 6 | pages = 682–686 | date = June 1987 | doi = 10.1136/jnnp.50.6.682 | pmid = 3302110 | pmc = 1032070 | url = https://jnnp.bmj.com/content/50/6/682 }}</ref> 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.<ref name="AdisInsight-Gabapentin">{{cite web | title = Drug Profile: Gabapentin | url = https://adisinsight.springer.com/drugs/800002421 | work = Adis Insight }}</ref> Approval by the [[U.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.<ref name="Mack">{{cite journal | vauthors = Mack A | title = Examination of the evidence for off-label use of gabapentin | journal = Journal of Managed Care Pharmacy | volume = 9 | issue = 6 | pages = 559–568 | year = 2003 | pmid = 14664664 | doi = 10.18553/jmcp.2003.9.6.559 | pmc = 10437292 | url = http://www.amcp.org/data/jmcp/Contemporary%20Subject-559-568.pdf | url-status = dead | access-date = 15 August 2006 | archive-url = https://web.archive.org/web/20100917222044/http://amcp.org/data/jmcp/Contemporary%20Subject-559-568.pdf | archive-date = 17 September 2010 }}</ref><ref name="Neurontin label" /> Subsequently, gabapentin was approved in the United States for the treatment of pain from [[postherpetic neuralgia]] in 2002.<ref name="pmid23342236">{{cite journal | vauthors = Irving G | title = Once-daily gastroretentive gabapentin for the management of postherpetic neuralgia: an update for clinicians | journal = Therapeutic Advances in Chronic Disease | volume = 3 | issue = 5 | pages = 211–218 | date = September 2012 | pmid = 23342236 | pmc = 3539268 | doi = 10.1177/2040622312452905 }}</ref> A [[generic medication|generic version]] of gabapentin first became available in the United States in 2004.<ref name="Reed2012">{{cite book | vauthors = Reed D |title=The Other End of the Stethoscope: The Physician's Perspective on the Health Care Crisis|url=https://books.google.com/books?id=HkICcDDz0qQC&pg=PA63|date=2 March 2012|publisher=AuthorHouse|isbn=978-1-4685-4410-7|pages=63–}}</ref> 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.<ref name="GoodRx2013">{{cite web | vauthors = Orrange S | date = 31 May 2013 | title = Yabba Dabba Gabapentin: Are Gralise and Horizant Worth the Cost? | url = https://www.goodrx.com/blog/yabba-dabba-gabapentin-are-gralise-and-horizant-worth-the-cost/ | publisher = GoodRx, Inc. | access-date = 22 June 2018 | archive-url = https://web.archive.org/web/20180623032739/https://www.goodrx.com/blog/yabba-dabba-gabapentin-are-gralise-and-horizant-worth-the-cost/ | archive-date = 23 June 2018 | url-status = dead }}</ref><ref name="AdisInsight-Gabapentin-CR">{{cite web | title = Gabapentin controlled release – Depomed | url = http://adisinsight.springer.com/drugs/800019682 | work = Adis Insight }}</ref>

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.<ref>{{Cite news | vauthors = Span P |date=17 August 2024 |title=The Painkiller Used for Just About Anything |url=https://www.nytimes.com/2024/08/17/health/gabapentin-seniors-pain.html |access-date=21 December 2024 |work=The New York Times}}</ref>

==Society and culture==
===Legal status===

====United Kingdom====
Effective April 2019, the United Kingdom reclassified the drug as a [[Class C drug|class C controlled substance]].<ref>{{cite web|url=https://nursingnotes.co.uk/pregabalin-gabapentin-will-become-controlled-drugs-april/|title=Pregabalin and gabapentin will become controlled drugs in April|date=17 October 2018|website=NursingNotes|access-date=16 June 2019|archive-date=16 June 2019|archive-url=https://web.archive.org/web/20190616083615/https://nursingnotes.co.uk/pregabalin-gabapentin-will-become-controlled-drugs-april/|url-status=dead}}</ref><ref>{{cite web |url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/491854/ACMD_Advice_-_Pregabalin_and_gabapentin.pdf |title=Re: Pregabalin and Gabapentin advice |date=14 January 2016 |website=GOV.UK }}</ref><ref>{{cite web | title=Pregabalin and gabapentin: proposal to schedule under the Misuse of Drugs Regulations 2001 | website=GOV.UK | date=10 November 2017 | url=https://www.gov.uk/government/consultations/pregabalin-and-gabapentin-proposal-to-schedule-under-the-misuse-of-drugs-regulations-2001 | access-date=2 April 2020}}</ref><ref>{{cite journal | vauthors = Mayor S | title = Pregabalin and gabapentin become controlled drugs to cut deaths from misuse | journal = BMJ | volume = 363 | pages = k4364 | date = October 2018 | pmid = 30327316 | doi = 10.1136/bmj.k4364 | s2cid = 53520780 }}</ref><ref name="UK class C">{{cite web | title=Pregabalin and gabapentin to be controlled as Class C drugs | website=GOV.UK | date=15 October 2018 | url=https://www.gov.uk/government/news/pregabalin-and-gabapentin-to-be-controlled-as-class-c-drugs | access-date=2 April 2020}}</ref>

====United States====
Gabapentin is not a controlled substance under the federal [[Controlled Substances Act]].<ref>{{cite web|url=https://www.deadiversion.usdoj.gov/drug_chem_info/gabapentin.pdf|publisher=Drug Enforcement Administration|title=Gabapentin (Neurontin)|date=January 2023}}</ref> Effective 1 July 2017, Kentucky classified gabapentin as a [[Controlled Substances Act#Schedules of controlled substances|schedule V controlled substance]] statewide.<ref>{{cite web|url=https://pharmacy.ky.gov/Documents/Gabapentin%20-%20Schedule%20V%20Controlled%20Substance.pdf|title=Important Notice: Gabapentin Becomes a Schedule 5 Controlled Substance in Kentucky |date=March 2017|website=Kentucky State Board of Pharmacy |access-date=18 June 2018}}</ref> Gabapentin is scheduled V drug in other states such as West Virginia,<ref>{{cite web|title=WV Code 212|url=http://www.wvlegislature.gov/WVCODE/ChapterEntire.cfm?chap=60a&art=2&section=212|website=West Virginia Legislature |access-date=30 May 2020}}</ref> Tennessee,<ref>{{cite web|title=Gabapentin will be a Schedule V controlled substance in Tennessee effective July 1, 2018|url=https://www.tn.gov/content/dam/tn/health/healthprofboards/New%20Statue%20Gabapentin%2006-18.pdf|website=tn.gov|access-date=30 May 2020}}</ref> Alabama,<ref>{{cite web|title=Pharmacy Division |url=http://www.alabamapublichealth.gov/pharmacy/|website=Alabama Department of Public Health (ADPH) |access-date=30 May 2020}}</ref> Utah,<ref>{{cite web|title=Controlled Substances Amendments |url=https://le.utah.gov/~2024/bills/static/HB0260.html|website=Utah State Legislature |access-date=12 April 2024}}</ref> and Virginia.<ref>{{cite web|url=http://www.dhp.virginia.gov/Pharmacy/docs/gabapentin06172019.pdf|title=Scheduling of Gabapentin|access-date=28 June 2023|publisher=Virginia Department of Health Professions}}</ref>

===Off-label promotion===
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,<ref name="evid">{{cite journal | vauthors = Mack A | title = Examination of the evidence for off-label use of gabapentin | journal = Journal of Managed Care Pharmacy | volume = 9 | issue = 6 | pages = 559–568 | year = 2003 | pmid = 14664664 | doi = 10.18553/jmcp.2003.9.6.559 | pmc = 10437292 | s2cid = 17085492 }}</ref> the preponderance of evidence suggests that it is not effective.<ref>{{cite journal | vauthors = Reinares M, Rosa AR, Franco C, Goikolea JM, Fountoulakis K, Siamouli M, Gonda X, Frangou S, Vieta E | title = A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression | journal = The International Journal of Neuropsychopharmacology | volume = 16 | issue = 2 | pages = 485–496 | date = March 2013 | pmid = 22575611 | doi = 10.1017/S1461145712000491 | title-link = doi | doi-access = free }}</ref>

====''Franklin v. Parke-Davis'' case====
{{anchor|Franklin v. Pfizer}}
{{Main|Franklin v. Parke-Davis}}

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 the ''[[Franklin v. Parke-Davis]]'' case.

While off-label prescriptions are common for many drugs, marketing of off-label uses of a drug is not.<ref name=Hen2006 /> 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&nbsp;million in fines to settle civil and criminal charges regarding the marketing of Neurontin for off-label purposes. The 2004 settlement was [[List of largest pharmaceutical settlements|one of the largest]] in U.S. history up to that point, and the [[List of off-label promotion pharmaceutical settlements|first off-label promotion case]] brought successfully under the False Claims Act.<ref>{{cite news |url = http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2004/05/14/BUGKK6L0LB1.DTL |title = Huge penalty in drug fraud, Pfizer settles felony case in Neurontin off-label promotion |work = [[San Francisco Chronicle]] |date = 14 May 2004 |page = C-1 | vauthors = Tansey B |url-status=live |archive-url = https://web.archive.org/web/20060623103021/http://www.sfgate.com/cgi-bin/article.cgi?f=%2Fc%2Fa%2F2004%2F05%2F14%2FBUGKK6L0LB1.DTL |archive-date = 23 June 2006 }}</ref>

[[Kaiser Foundation Hospitals]] and [[Kaiser 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, and [[neuropathic pain]]).<ref name="Berkrot 20100325">{{cite news |url = https://www.reuters.com/article/pfizer-neurontin-idUSN259778920100325/|publisher = Reuters | vauthors = Berkrot B |title = US jury's Neurontin ruling to cost Pfizer $141 mln |date = 25 March 2010 |url-status=live |archive-url = https://web.archive.org/web/20151019112249/http://www.reuters.com/article/2010/03/25/pfizer-neurontin-idUSN259778920100325 |archive-date = 19 October 2015 }}</ref><ref name=AP2010Jury>{{cite news |title = Pfizer faces $142M in damages for drug fraud |url = http://www.businessweek.com/ap/financialnews/D9ELVKG80.htm |newspaper = [[Bloomberg Businessweek]] |date = 25 March 2010 |access-date = 13 January 2012 |url-status=dead |archive-url = https://web.archive.org/web/20151019112248/http://www.businessweek.com/ap/financialnews/D9ELVKG80.htm |archive-date = 19 October 2015 }}</ref><ref>{{cite news |title = Pfizer Told to Pay $142.1 Million for Neurontin Marketing Fraud | vauthors = Van Voris B, Lawrence J |url = https://www.bloomberg.com/apps/news?pid=email_en&sid=a_9aVylZQGjU |website = [[Bloomberg News]] |date = 26 March 2010 |access-date = 13 January 2012 |url-status=dead |archive-url = https://web.archive.org/web/20130513232138/http://www.bloomberg.com/apps/news?pid=email_en&sid=a_9aVylZQGjU |archive-date = 13 May 2013 }}</ref> In 2010, a federal jury in Massachusetts ruled in Kaiser's favor, finding that Pfizer violated the federal [[Racketeer Influenced and Corrupt Organizations Act|Racketeer Influenced and Corrupt Organizations]] (RICO) Act and was liable for {{US$|47.36 million}} in damages, which was [[Treble damages|automatically trebled]] to just under $142.1 million.<ref name=AP2010Jury/><ref name="Berkrot 20100325"/> [[Aetna, Inc.]] and a group of [[Employer-sponsored health insurance|employer health plans]] prevailed in their similar Neurontin-related claims against Pfizer.<ref name=Husgen>{{cite news| vauthors =  Husgen J |url=https://www.healthcarelawinsights.com/2013/10/pfizer-appeal-targets-fraudulent-drug-marketing-claims-brought-under-civil-rico-statute/|work=Healthcare Law Insights|publisher=[[Hugh Blackwell]]|title=Pfizer Appeal Targets Fraudulent Drug Marketing Claims Brought Under Civil RICO Statute|date=3 October 2013}}</ref> Pfizer appealed, but the [[U.S. Court of Appeals for the First Circuit]] upheld the verdict,<ref name=Husgen/> and in 2013, the [[US Supreme Court]] declined to hear the case.<ref>{{cite news| vauthors =  Hurley L |url=https://www.reuters.com/article/idUSBRE9B80K1/|title=US high court leaves intact $142 million verdict against Pfizer|work=Reuters|date=9 December 2013}}</ref><ref>{{cite web|url=https://www.scotusblog.com/case-files/cases/pfizer-inc-v-kaiser-foundation-health-plan-inc/|title=Pfizer Inc. v. Kaiser Foundation Health Plan, Inc.: Petition for certiorari denied on December 9, 2013|work=[[SCOTUSBlog]]}}</ref>

====Gabasync====

[[Gabasync]], a treatment consisting of a combination of gabapentin and two other medications ([[flumazenil]] and [[hydroxyzine]]) as well as therapy, is an ineffective treatment promoted for [[methamphetamine]] addiction, though it had also been claimed to be effective for [[Physical dependence|dependence]] on alcohol or [[cocaine]].<ref name = "Pelley_2007" /> It was marketed as PROMETA. While the individual drugs had been approved by the FDA, their off-label use for addiction treatment has not.<ref>{{cite web | title = Prometa Founder's Spotty Background Explored | date = 3 November 2006 | url = http://www.drugfree.org/join-together/prometa-founders-spotty-background-explored/ | archive-url= https://web.archive.org/web/20150923220715/http://www.drugfree.org/join-together/prometa-founders-spotty-background-explored/ | archive-date = 23 September 2015 }}</ref> Gabasync was marketed by Hythiam, Inc. which is owned by [[Terren Peizer]], a former [[junk bond]] salesman who has since been convicted of securities fraud relative to another company.<ref>Dave Michaels (21 June 2024). [https://www.wsj.com/finance/regulation/jury-convicts-milken-protege-terren-peizer-of-insider-trading-7c78ba2a "Jury Convicts Milken Protégé Terren Peizer of Insider Trading,"] ''The Wall Street Journal''.</ref><ref>{{Cite web|url=https://ktla.com/news/local-news/santa-monica-man-used-anti-insider-trading-measure-to-commit-fraud-doj/|title=Santa Monica man used anti-insider-trading measure to commit fraud: DOJ|date=1 March 2023|access-date=30 March 2023|archive-date=28 March 2023|archive-url=https://web.archive.org/web/20230328043228/https://ktla.com/news/local-news/santa-monica-man-used-anti-insider-trading-measure-to-commit-fraud-doj/|url-status=live}}</ref><ref>{{cite web|url=https://www.justice.gov/criminal-vns/case/united-states-v-terren-s-peizer|title=United States V. Terren S. Peizer |date=1 March 2023|website=www.justice.gov}}</ref><ref name = "Pelley_2007">{{cite web | veditors = Pelley S | title = Prescription For Addiction | work = 60 Minutes | publisher = CBS News | url = http://www.cbsnews.com/news/prescription-for-addiction/ | date = 7 December 2007 }}</ref> Hythiam charges up to $15,000 per patient to license its use (of which half goes to the prescribing physician, and half to Hythiam).<ref>{{cite journal |title=Prometa under fire in Washington drug court program|journal=Alcoholism & Drug Abuse Weekly|volume=20|issue=3|date=21 January 2008|doi=10.1002/adaw.20121 }}</ref>

In a November 2005 article entitled "Curb Your Cravings For This Stock", ''[[Barron's (newspaper)|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".<ref name="Alpert_2005">{{cite web|url=https://www.wsj.com/articles/SB113115427427989094|title=Curb Your Cravings For This Stock| vauthors = Alpert B | work =The Wall Street Journal|date=7 November 2005}}</ref> ''[[60 Minutes]]'', ''[[NBC News]]'', and ''[[The Dallas Morning News]]'' criticized Peizer after the company bypassed [[clinical studies]] and government approval when bringing to market Prometa; the addiction drug proved to be completely ineffective.<ref name="Huus_2007">{{cite web|url=http://www.nbcnews.com/health/health-news/unproven-meth-cocaine-remedy-hits-market-flna1C9444547|title=Unproven meth, cocaine 'remedy' hits market|website=NBC News|date=5 February 2007| vauthors = Huus K }}</ref><ref>{{cite news|url=http://washingtonmonthly.com/2012/01/24/the-rise-and-fall-of-a-miracle-cure-for-drug-addiction/|title=The Rise and Fall of a "Miracle Cure" for Drug Addiction| vauthors = Humphreys K |date=24 January 2012|work=Washington Monthly}}</ref><ref name = "Pelley_2007" /><ref name="Dallas">{{cite news | vauthors = Ramshaw E |date=20 January 2008 |title=Texas' Prometa program for treating meth addicts draws skeptics |work=Dallas Morning News |url=https://www.dallasnews.com/sharedcontent/dws/dn/latestnews/stories/012108dntexprometa.2c2f801.html |archive-url=https://web.archive.org/web/20101027101333/https://www.dallasnews.com/sharedcontent/dws/dn/latestnews/stories/012108dntexprometa.2c2f801.html |archive-date=27 October 2010}}</ref> [[CBS News]] journalist [[Scott Pelley]] said to Peizer in 2007: "Depending on who you talk to, you're either a revolutionary or a [[snake oil salesman]]."<ref name="Schuster_2007">{{cite web | vauthors = Schuster H, Peterson R |url=https://www.cbsnews.com/news/prescription-for-addiction/|title=Prescription For Addiction|website=CBS News|date=7 December 2007}}</ref><ref name="Alpert_2005"/> Journalist [[Adam Feuerstein]] opined: "most of what Peizer says is dubious-sounding hype".<ref>{{cite web | vauthors = [[Adam Feuerstein|Feuerstein A]] | date = 13 November 2007 | url = https://www.thestreet.com/investing/stocks/biotech-notebook-hythiam-shire-genentech-10389850 | work = Biotech Notebook | title = Hythiam, Shire, Genentech; Talk is proving cheap at Hythiam | publisher = TheStreet }}</ref>

In November 2011, the results of a [[Blinded experiment|double-blind]], [[placebo-controlled study]] (financed by Hythiam and carried out at [[UCLA]]) were published in the [[peer-reviewed]] journal ''[[Addiction (journal)|Addiction]]''. 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."<ref>{{cite journal | vauthors = Ling W, Shoptaw S, Hillhouse M, Bholat MA, Charuvastra C, Heinzerling K, Chim D, Annon J, Dowling PT, Doraimani G | title = Double-blind placebo-controlled evaluation of the PROMETA™ protocol for methamphetamine dependence | journal = Addiction | volume = 107 | issue = 2 | pages = 361–369 | date = February 2012 | pmid = 22082089 | pmc = 4122522 | doi = 10.1111/j.1360-0443.2011.03619.x }}</ref>

==== Usage trends ====
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.<ref>{{cite journal | vauthors = Chan AY, Yuen AS, Tsai DH, Lau WC, Jani YH, Hsia Y, Osborn DP, Hayes JF, Besag FM, Lai EC, Wei L, Taxis K, Wong IC, Man KK | title = Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study | journal = Nature Communications | volume = 14 | issue = 1 | pages = 5005 | date = August 2023 | pmid = 37591833 | pmc = 10435503 | doi = 10.1038/s41467-023-40637-8 | bibcode = 2023NatCo..14.5005C |url=https://pure.rug.nl/ws/files/799417606/s41467-023-40637-8.pdf }}</ref>

===Brand names===
Gabapentin was originally marketed under the brand name Neurontin. Since it became generic, it has been marketed worldwide using over 300 different brand names.<ref name="Drugs.com" >{{cite web | url = https://www.drugs.com/international/gabapentin.html | work = Drugs.com | title = International listings for Gabapentin | archive-url = https://web.archive.org/web/20160216074247/http://www.drugs.com/international/gabapentin.html | archive-date=16 February 2016 | access-date = 9 February 2016 }}</ref> An [[extended-release]] formulation of gabapentin for once-daily administration was introduced in 2011, for postherpetic neuralgia under the brand name Gralise.<ref name="Drugs.com-History">{{cite web | title = Gralise Approval History | url = https://www.drugs.com/history/gralise.html | publisher = Drugs.com }}</ref>

In the US, Neurontin is marketed by [[Viatris]] after [[Upjohn]] was spun off from Pfizer.<ref>{{cite web | title=Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan | publisher=Pfizer | via=Business Wire | date=16 November 2020 | url=https://www.businesswire.com/news/home/20201116005378/en/ | access-date=17 June 2024}}</ref><ref>{{cite web | title=Neurontin | website=Pfizer | url=https://www.pfizer.com/products/product-detail/neurontin | access-date=17 June 2024}}</ref><ref>{{cite web | title=Brands | website=Viatris | date=16 November 2020 | url=https://www.viatris.com/en/products/brands | access-date=17 June 2024}}</ref>

===Related drugs===
Parke-Davis developed a drug called [[pregabalin]], which is related in structure to gabapentin, as a successor to gabapentin.<ref name="Baillie 33–9">{{cite journal | vauthors = Baillie JK, Power I | title = The mechanism of action of gabapentin in neuropathic pain | journal = Current Opinion in Investigational Drugs | volume = 7 | issue = 1 | pages = 33–39 | date = January 2006 | pmid = 16425669 }}</ref> Another similar drug [[atagabalin]] has been unsuccessfully tried by Pfizer as a treatment for insomnia.<ref name="pmid21681607">{{cite journal | vauthors = Kjellsson MC, Ouellet D, Corrigan B, Karlsson MO | title = Modeling sleep data for a new drug in development using markov mixed-effects models | journal = Pharmaceutical Research | volume = 28 | issue = 10 | pages = 2610–2627 | date = October 2011 | pmid = 21681607 | doi = 10.1007/s11095-011-0490-x | s2cid = 22241527 }}</ref> A [[prodrug]] form ([[gabapentin enacarbil]])<ref name="pmid19787095">{{cite journal | vauthors = Landmark CJ, Johannessen SI | title = Modifications of antiepileptic drugs for improved tolerability and efficacy | journal = Perspectives in Medicinal Chemistry | volume = 2 | pages = 21–39 | date = February 2008 | pmid = 19787095 | pmc = 2746576 | doi = 10.1177/1177391X0800200001 }}</ref> was approved by the U.S. [[Food and Drug Administration]] (FDA).

===Recreational use===
{{Globalize section|date=August 2024|US}}
When taken in excess, gabapentin can induce euphoria, a sense of calm, improved sociability, and reduced alcohol or cocaine cravings.<ref name="pmid22867659">{{cite journal | vauthors = Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J | title = Substance misuse of gabapentin | journal = The British Journal of General Practice | volume = 62 | issue = 601 | pages = 406–407 | date = August 2012 | pmid = 22867659 | pmc = 3404313 | doi = 10.3399/bjgp12X653516 }}</ref><ref>{{cite journal | vauthors = Shebak S, Varipapa R, Snyder A, Whitham MD, Milam TR | url = https://pdfs.semanticscholar.org/9bab/627065e943e1508057231c865569bf20f5d3.pdf | title = Gabapentin abuse and overdose: a case report | journal = J Subst Abus Alcohol | date = 2014 | volume = 2 | pages = 1018 | s2cid = 8959463 | archive-url = https://web.archive.org/web/20190302115335/https://pdfs.semanticscholar.org/9bab/627065e943e1508057231c865569bf20f5d3.pdf | archive-date = 2 March 2019 }}</ref><ref name="pmid31291212">{{cite journal | vauthors = Martinez GM, Olabisi J, Ruekert L, Hasan S | title = A Call for Caution in Prescribing Gabapentin to Individuals With Concurrent Polysubstance Abuse: A Case Report | journal = Journal of Psychiatric Practice | volume = 25 | issue = 4 | pages = 308–312 | date = July 2019 | pmid = 31291212 | doi = 10.1097/PRA.0000000000000403 | s2cid = 195878855 }}</ref> Also known on the streets as "Gabbies",<ref>{{cite book | title = Oxford Textbook of Correctional Psychiatry | vauthors = Trestman RL, Appelbaum KL, Metzner JL | publisher = Oxford University Press | date = April 2015 | page = 167 | isbn= 978-0-19-936057-4}}</ref> gabapentin was reported in 2017 to be increasingly abused and misused for these euphoric effects.<ref>{{cite journal | vauthors = Goodman CW, Brett AS | title = Gabapentin and Pregabalin for Pain - Is Increased Prescribing a Cause for Concern? | journal = The New England Journal of Medicine | volume = 377 | issue = 5 | pages = 411–414 | date = August 2017 | pmid = 28767350 | doi = 10.1056/NEJMp1704633 | title-link = doi | doi-access = free }}</ref><ref>{{cite journal | vauthors = Evoy KE, Morrison MD, Saklad SR | title = Abuse and Misuse of Pregabalin and Gabapentin | journal = Drugs | volume = 77 | issue = 4 | pages = 403–426 | date = March 2017 | pmid = 28144823 | doi = 10.1007/s40265-017-0700-x | s2cid = 24396685 }}</ref> 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.<ref name="pmid26721643" /><ref name="pmid29179227">{{cite journal | vauthors = Bonnet U, Scherbaum N | title = [On the risk of dependence on gabapentinoids] | language = de | journal = Fortschritte der Neurologie-Psychiatrie | volume = 86 | issue = 2 | pages = 82–105 | date = February 2018 | pmid = 29179227 | doi = 10.1055/s-0043-122392 }}</ref> Gabapentin misuse, toxicity, and use in suicide attempts among adults in the US increased from 2013 to 2017.<ref>{{cite journal | vauthors = Reynolds K, Kaufman R, Korenoski A, Fennimore L, Shulman J, Lynch M | title = Trends in gabapentin and baclofen exposures reported to U.S. poison centers | journal = Clinical Toxicology | volume = 58 | issue = 7 | pages = 763–772 | date = July 2020 | pmid = 31786961 | doi = 10.1080/15563650.2019.1687902 | s2cid = 208537638 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Faryar KA, Webb AN, Bhandari B, Price TG, Bosse GM | title = Trending gabapentin exposures in Kentucky after legislation requiring the use of the state prescription drug monitoring program for all opioid prescriptions | journal = Clinical Toxicology | volume = 57 | issue = 6 | pages = 398–403 | date = June 2019 | pmid = 30676102 | doi = 10.1080/15563650.2018.1538518 | s2cid = 59226292 }}</ref>

Withdrawal symptoms, often resembling those of [[Benzodiazepine withdrawal syndrome|benzodiazepine withdrawal]], play a role in the physical dependence some users experience.<ref name="Bonnet_2017" /> Its misuse predominantly coincides with the usage of other [[CNS depressant]] drugs, namely opioids, benzodiazepines, and alcohol.<ref>{{cite journal | vauthors = Smith RV, Havens JR, Walsh SL | title = Gabapentin misuse, abuse and diversion: a systematic review | journal = Addiction | volume = 111 | issue = 7 | pages = 1160–1174 | date = July 2016 | pmid = 27265421 | pmc = 5573873 | doi = 10.1111/add.13324 }}</ref>

==Veterinary use==
In cats, gabapentin can be used as an analgesic in multi-modal pain management,<ref name="pmid21831060">{{cite journal | vauthors = Vettorato E, Corletto F | title = Gabapentin as part of multi-modal analgesia in two cats suffering multiple injuries | journal = Veterinary Anaesthesia and Analgesia | volume = 38 | issue = 5 | pages = 518–520 | date = September 2011 | pmid = 21831060 | doi = 10.1111/j.1467-2995.2011.00638.x }}</ref> anxiety medication to reduce stress during travel or vet visits,<ref name="pmid29099247">{{cite journal | vauthors = van Haaften KA, Forsythe LR, Stelow EA, Bain MJ | title = Effects of a single preappointment dose of gabapentin on signs of stress in cats during transportation and veterinary examination | journal = Journal of the American Veterinary Medical Association | volume = 251 | issue = 10 | pages = 1175–1181 | date = November 2017 | pmid = 29099247 | doi = 10.2460/javma.251.10.1175 | s2cid = 7780988 }}</ref> and anticonvulsant.<ref name=plumbs>{{cite web |title=Gabapentin |url=https://www.plumbsveterinarydrugs.com/#!/veterinarymedicationguides |website=Plumb's Veterinary Drugs |access-date=2 April 2021}}</ref>

Veterinarians may prescribe gabapentin as an anticonvulsant and pain reliever in dogs.<ref name="Coile_2022" /><ref name="plumbs" /> It has beneficial effects for treating [[Epilepsy in animals|epilepsy]], different kinds of pain ([[Chronic pain|chronic]], [[Neuropathic pain|neuropathic]], and post-operative pain), and anxiety, lip-licking behaviour, storm phobia, fear-based aggression.<ref>{{cite journal | vauthors = Di Cesare F, Negro V, Ravasio G, Villa R, Draghi S, Cagnardi P | title = Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses | journal = Animals | volume = 13 | issue = 12 | pages = 2045 | date = June 2023 | pmid = 37370556 | pmc = 10295034 | doi = 10.3390/ani13122045 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kirby-Madden T, Waring CT, Herron M | title = Effects of Gabapentin on the Treatment of Behavioral Disorders in Dogs: A Retrospective Evaluation | journal = Animals | volume = 14 | issue = 10 | pages = 1462 | date = May 2024 | pmid = 38791679 | pmc = 11117262 | doi = 10.3390/ani14101462 | doi-access = free }}</ref>

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.<ref name="Coile_2022">{{cite web | vauthors = Coile C | date = 31 October 2022 |title=Gabapentin for Dogs: Uses and Side Effects |url=https://www.akc.org/expert-advice/health/gabapentin-for-dogs/ |access-date=12 May 2023 |website=American Kennel Club |archive-url=https://web.archive.org/web/20221206075825/https://www.akc.org/expert-advice/health/gabapentin-for-dogs/ |archive-date=6 December 2022 |url-status=live }}</ref><ref name="plumbs" />

== See also ==
* {{Portal inline| Medicine}}

== References ==
{{Reflist}}

== External links ==
{{Scholia|topic}}

{{Navboxes
| title = [[Medicine|Medical uses]]
| titlestyle = background:#ccccff
| list1 = 
{{Anticonvulsants}}
{{Anxiolytics}}
{{Neuropathic pain and fibromyalgia pharmacotherapies}}
}}
{{Navboxes
| title = [[Recreational drug use|Recreational uses]]
| titlestyle = background:#ccccff
| list1 = 
{{Euphoriants}}
{{Recreational drug use}}
}}
{{Ion channel modulators}}
{{Chemical classes of psychoactive drugs}}
{{Authority control}}

[[Category:Analgesics]]
[[Category:Anticonvulsants]]
[[Category:Anxiolytics]]
[[Category:Calcium channel blockers]]
[[Category:Drugs developed by Pfizer]]
[[Category:GABA analogues]]
[[Category:Gamma-Amino acids]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Aminomethyl compounds]]