Gabapentin

Gabapentin is recommended for use in focal seizures and neuropathic pain.{{cite web |url=https://www.nice.org.uk/guidance/cg173/chapter/1-Recommendations |title=1 Recommendations | Neuropathic pain in adults: pharmacological management in non-specialist settings | Guidance |website=National Institute for Health and Care Excellence (NICE) |date=20 November 2013 |access-date=14 December 2020}} Gabapentin is prescribed off-label in the US and the UK,{{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 }}{{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 }} for example, for the treatment of non-neuropathic pain, anxiety disorders, sleep problems and bipolar disorder.{{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 }} In recent years, gabapentin has seen increased use, particularly in the elderly.{{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}} 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.{{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 }} 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.{{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 }}

Gabapentin is approved for the treatment of focal seizures;{{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 }} however, it is not effective for generalized epilepsy.{{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 }}

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

Regarding the specific diagnoses, a systematic review has found evidence for gabapentin to provide pain relief for some people with postherpetic neuralgia and diabetic neuropathy.{{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 }} Gabapentin is approved for the former indication in the US. In addition to these two neuropathies, European Federation of Neurological Societies guideline notes gabapentin effectiveness for central pain. A combination of gabapentin with an opioid or nortriptyline may work better than either drug alone.

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.

Evidence finds little or no benefit and significant risk in those with chronic low back pain or sciatica.{{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 }}{{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 }} Gabapentin is not effective in HIV-associated sensory neuropathy{{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 }} and neuropathic pain due to cancer.{{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 }}

There is a small amount of research on the use of gabapentin for the treatment of anxiety disorders.{{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 }}{{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 }}

Gabapentin is effective for the long-term treatment of social anxiety disorder and in reducing preoperative anxiety.{{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 }}{{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 }}

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

For panic disorder, gabapentin has produced mixed results.

Gabapentin is effective in treating sleep disorders such as insomnia and restless legs syndrome that are the result of an underlying illness, but comes with some risk of discontinuation and withdrawal symptoms after prolonged use at higher doses.{{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 }}

Gabapentin enhances slow-wave sleep in people with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal.{{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 }}

Gabapentin is moderately effective in reducing the symptoms of alcohol withdrawal and associated craving.{{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 }}{{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 }}{{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 }} 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.{{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 }}

Gabapentin is ineffective in cocaine dependence and methamphetamine use,{{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 }} and it does not increase the rate of smoking cessation.{{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 }} While some studies indicate that gabapentin does not significantly reduce the symptoms of opiate withdrawal, there is increasing evidence that gabapentinoids are effective in controlling some of the symptoms during opiate detoxification. A clinical study in Iran, where heroin dependence is a significant social and public health problem, showed gabapentin produced positive results during an inpatient therapy program, particularly by reducing opioid-induced hyperalgesia and drug craving.{{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 }} There is insufficient evidence for its use in cannabis dependence.{{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 }}

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.{{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 }}{{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 }}{{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 }}

Gabapentin decreases the frequency of hot flashes in both menopausal women and people with breast cancer. However, antidepressants have similar efficacy, and treatment with estrogen more effectively prevents hot flashes.{{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 }}

Gabapentin reduces spasticity in multiple sclerosis and is prescribed as one of the first-line options.{{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/ }} It is an established treatment of restless legs syndrome.{{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)^§ | journal = Movement Disorders | volume = 33 | issue = 7 | pages = 1077–1091 | date = July 2018 | pmid = 29756335 | doi = 10.1002/mds.27260 | s2cid = 21669996 }} Gabapentin alleviates itching in kidney failure (uremic pruritus){{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 }}{{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 }} and itching of other causes.{{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 }} It may be an option in essential or orthostatic tremor.{{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 }}{{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 }}{{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 }}

Gabapentin does not appear to provide benefit for bipolar disorder,{{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 }} complex regional pain syndrome,{{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 }} post-surgical pain,{{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 }} or tinnitus,{{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) }} or prevent episodic migraine in adults.{{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 }}

Gabapentin should be used carefully and at lower doses in people with kidney problems due to possible accumulation and toxicity. It is unclear if it is safe during pregnancy or breastfeeding.

File:Gabapentin Orion bottle.jpg

Dizziness and somnolence are the most frequent side effects. Fatigue, ataxia, peripheral edema (swelling of extremities), and nystagmus are also common. A 2017 meta-analysis found that gabapentin also increased the risk of difficulties in mentation and visual disturbances as compared to a placebo. Gabapentin is associated with a weight gain of {{convert|2.2|kg|lb|abbr=on}} after 1.5 months of use.{{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 }} Case studies indicate that it may cause anorgasmia and erectile dysfunction,{{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 }} as well as myoclonus{{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 }}{{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 }} that disappear after discontinuing gabapentin or replacing it with other medication. Fever, swollen glands that do not go away, eyes or skin turning yellow, unusual bruises or bleeding, unexpected muscle pain or weakness, rash, long-lasting stomach pain which may indicate an inflamed pancreas, hallucinations, anaphylaxis, respiratory depression, and increased suicidal ideation are rare but serious side effects.{{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}}

As with all antiepileptic drugs approved in the US, gabapentin label contains a warning of an increased risk of suicidal thoughts and behaviors.{{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}} This warning is based on a meta-analysis of all approved antiepileptic drugs in 2008, and not with gabapentin alone. According to an experimental meta-analysis of insurance claims 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.{{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 = }} 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.{{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 }} 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.{{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 }} On the other hand, a study published by the Harvard Data Science Review found that gabapentin was associated with a significantly reduced rate of suicide.Gibbons, R., Hur, K., Lavigne, J., Wang, J., & Mann, J. J. (2019). Medications and Suicide: High Dimensional Empirical Bayes Screening (iDEAS). Harvard Data Science Review, 1(2). https://doi.org/10.1162/99608f92.6fdaa9de

Serious breathing suppression, potentially fatal, may occur when gabapentin is taken together with opioids, benzodiazepines, or other depressants, or by people with underlying lung problems such as COPD.{{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}} Gabapentin and opioids are commonly prescribed or abused together, and research indicates that the breathing suppression they cause is additive. For example, gabapentin use before joint replacement or laparoscopic surgery increased the risk of respiratory depression by 30–60%. A Canadian study showed that use of gabapentin and other gabapentinoids, whether for epilepsy, neuropathic pain or other chronic pain was associated with a 35–58% increased risk for severe exacerbation of pre-existing chronic obstructive pulmonary disease.{{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 }}

Withdrawal symptoms typically occur 1–2 days after abruptly stopping gabapentin (almost unambiguously due to extended use and during a very short-term rebound phenomenon) {{emdash}} similar to, albeit less intense than most benzodiazepines.{{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 }} Agitation, confusion and disorientation are the most frequently reported, followed by gastrointestinal complaints and sweating, and more rare tremor, tachycardia, hypertension and insomnia. In some cases, users experience withdrawal seizures after chronic or semi-chronic use in the absence of periodic cycles or breaks during repeating and consecutive use.{{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 }} All these symptoms subside when gabapentin is re-instated or 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. In these persons, gabapentin can boost the opioid "high" as well as decrease commonly experienced opioid-withdrawal symptoms such as anxiety.{{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 }}

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, irritability, mood instability, and suicidal ideation, with some cases noting the emergence of mania, hallucinations, and psychosis, particularly in pediatric populations and individuals with preexisting psychiatric conditions.{{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 = }}{{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}}{{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}}

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.{{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 = }} 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.{{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 = }}{{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 = }}

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 or opioids.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}}.

Gabapentin, prevents seizures in a dose-related manner in several laboratory animal models.{{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 }} 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 "kindled" to produce focal seizures by repeated prior electrical stimulation of the hippocampus. Gabapentin slightly increased spontaneous 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 for producing ataxia.

Gabapentin also has been tested in a wide variety of animal models that are relevant for analgesic actions.{{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 }} Generally, gabapentin is not active to prevent pain-related behaviors in models of acute nociceptive pain, but it prevents pain-related behaviors when animals are made sensitive by prior peripheral inflammation or peripheral nerve damage (inflammatory or neuropathic conditions).

Gabapentin is a ligand of the α₂δ calcium channel subunit.{{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 }}{{cite journal | vauthors = Calandre EP, Rico-Villademoros F, Slim M | title = Alpha₂delta 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 }} The α₂δ-1 protein is coded by the CACNA2D1 gene. α₂δ was first described as an auxiliary protein connected to the main α₁ subunit (the channel-forming protein) of high voltage activated voltage-dependent calcium channels (L-type, N-type, P/Q type, and R-type).{{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 }} The same α₂δ protein has more recently been shown to interact directly with some NMDA-type and AMPA-type glutamate receptors at presynaptic sites and also with thrombospondin (an extracellular matrix protein secreted by astroglial cells).{{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 }}

Gabapentin is not a direct calcium channel blocker: it exerts its actions by disrupting the regulatory function of α₂δ and its interactions with other proteins. Gabapentin reduces delivery of intracellular calcium channels to the cell membrane, reduces the activation of the channels by the α₂δ subunit, decreases signaling leading to neurotransmitters release, and disrupts interactions of α₂δ with voltage gated calcium channels but also with NMDA receptors, neurexins, and thrombospondin.{{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 }}{{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 }} 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 neurotransmitters from presynaptic vesicles into the synaptic space.{{citation needed|date=February 2025}}

Out of the four known isoforms of α₂δ protein, gabapentin binds with similar high affinity to two: α₂δ-1 and α₂δ-2. All of the pharmacological properties of gabapentin tested to date are explained by its binding to just one isoform – α₂δ-1.

The endogenous α-amino acids L-leucine and L-isoleucine, which resemble gabapentin in chemical structure, bind α₂δ with similar affinity to gabapentin and are present in human cerebrospinal fluid at micromolar concentrations.{{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 }} They may be the endogenous ligands of the α₂δ subunit, and they competitively antagonize the effects of gabapentin.{{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 }} Accordingly, while gabapentin has nanomolar affinity for the α₂δ subunit, its potency in vivo is in the low micromolar range, and competition for binding by endogenous L-amino acids is likely to be responsible for this discrepancy.

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.{{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 }}

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

Even though gabapentin is a structural GABA analogue, and despite its name, it does not bind to the GABA receptors, does not convert into {{abbrlink|GABA|γ-aminobutyric acid}} or another GABA receptor agonist in vivo, and does not modulate GABA transport or metabolism within the range of clinical dosing. In vitro gabapentin has been found to very weakly inhibit the GABA aminotransferase enzyme (K_i = 17–20 mM), however, this effect is so weak it is not clinically relevant at prescribed doses.

Gabapentin is absorbed from the intestines by an active transport process mediated via an amino acid transporter, presumably, LAT2.{{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 }} As a result, the pharmacokinetics of gabapentin is dose-dependent, with diminished bioavailability and delayed peak levels at higher doses.

The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule.{{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 }} 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 mg dose of gabapentin increased by 50%.

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

Gabapentin can cross the blood–brain barrier and enter the central nervous system. Gabapentin concentration in cerebrospinal fluid is approximately 9–14% of its blood plasma concentration. Due to its low lipophilicity, gabapentin requires active transport across the blood–brain barrier.{{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 }}{{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 }}{{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 }} The LAT1 is highly expressed at the blood–brain barrier{{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 }} and transports gabapentin across into the brain. As with intestinal absorption mediated by an amino acid transporter, the transport of gabapentin across the blood–brain barrier by LAT1 is saturable. Gabapentin does not bind to other drug transporters such as P-glycoprotein (ABCB1) or OCTN2 (SLC22A5). It is not significantly bound to plasma proteins (<1%).

Gabapentin undergoes little or no metabolism.

Gabapentin is generally safe in people with liver cirrhosis.{{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 }}

Gabapentin is eliminated renally in the urine. It has a relatively short elimination half-life, with the reported average value of 5 to 7 hours. Because of its short elimination half-life, gabapentin must be administered 3 to 4 times per day to maintain therapeutic levels.{{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 }} Gabapentin XR (brand name Gralise) is taken once a day.{{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–}}

File:gaba and gabapentin.png

Gabapentin is a 3,3-disubstituted derivative of GABA. Therefore, it is a GABA analogue, as well as a γ-amino acid.{{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}}{{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}} It is similar to several other compounds that collectively are called gabapentinoids. Specifically, it is a derivative of GABA with a pentyl disubstitution at 3 position, hence, the name - gabapentin, in such a way as to form a six-membered ring. After the formation of the ring, the amine and carboxylic groups are not in the same relative positions as they are in the GABA;{{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}} they are more conformationally constrained.{{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 }}

Although it has been known for some time that gabapentin must bind to the α₂δ-1 protein in order to act pharmacologically (see Pharmacodynamics), the three-dimensional structure of the α₂δ-1 protein with gabapentin bound (or alternatively, the native amino acid, L-Isoleucine bound) has only recently been obtained by cryo-electron microscopy.{{cite journal | vauthors = Chen Z, Mondal A, Minor DL | title = Structural basis for Ca_Vα₂δ: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 }} 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 α1 subunit) on the calcium channel and chemotaxis (Cache1) domain of α₂δ-1.

File:synthesis of gabapentin.png

A process for chemical synthesis and isolation of gabapentin with high yield and purity{{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 }} 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.

GABA is the principal inhibitory neurotransmitter in mammalian brain. By the early 1970s, it was appreciated that there are two main classes of GABA receptors, GABA_A and GABA_B and also that baclofen was an agonist of GABA_B receptors. Gabapentin was designed, synthesized and tested in mice by researchers at the pharmaceutical company Goedecke AG in Freiburg, Germany (a subsidiary of Parke-Davis). It was meant to be an 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{{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}} by Satzinger and Hartenstein.{{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–}}

The first pharmacology findings published were sedating properties and prevention of seizures in mice evoked by the GABA antagonist, thiosemicarbazide. Shortly after, gabapentin was shown in vitro to reduce the release of the neurotransmitter dopamine from slices of rat caudate nucleus (striatum).{{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 }} This study provided evidence that the action of gabapentin, unlike baclofen, did not arise from the GABA_B receptor.

Initial clinical trials utilizing small numbers of subjects were for treatment of spasticity{{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 }} and migraine{{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}} 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.{{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 }} 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.{{cite web | title = Drug Profile: Gabapentin | url = https://adisinsight.springer.com/drugs/800002421 | work = Adis Insight }} 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.{{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 }} Subsequently, gabapentin was approved in the United States for the treatment of pain from postherpetic neuralgia in 2002.{{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 }} A generic version of gabapentin first became available in the United States in 2004.{{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–}} 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.{{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 }}{{cite web | title = Gabapentin controlled release – Depomed | url = http://adisinsight.springer.com/drugs/800019682 | work = Adis Insight }}

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.{{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}}

Effective April 2019, the United Kingdom reclassified the drug as a class C controlled substance.{{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}}{{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 }}{{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}}{{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 }}{{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}}

Gabapentin is not a controlled substance under the federal Controlled Substances Act.{{cite web|url=https://www.deadiversion.usdoj.gov/drug_chem_info/gabapentin.pdf|publisher=Drug Enforcement Administration|title=Gabapentin (Neurontin)|date=January 2023}} Effective 1 July 2017, Kentucky classified gabapentin as a schedule V controlled substance statewide.{{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}} Gabapentin is scheduled V drug in other states such as West Virginia,{{cite web|title=WV Code 212|url=http://www.wvlegislature.gov/WVCODE/ChapterEntire.cfm?chap=60a&art=2§ion=212|website=West Virginia Legislature |access-date=30 May 2020}} Tennessee,{{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}} Alabama,{{cite web|title=Pharmacy Division |url=http://www.alabamapublichealth.gov/pharmacy/|website=Alabama Department of Public Health (ADPH) |access-date=30 May 2020}} Utah,{{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}} and Virginia.{{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}}

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,{{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 }} the preponderance of evidence suggests that it is not effective.{{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 }}

{{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. In 2004, Warner-Lambert (which subsequently was acquired by Pfizer) agreed to plead guilty for activities of its Parke-Davis subsidiary, and to pay $430 million in fines to settle civil and criminal charges regarding the marketing of Neurontin for off-label purposes. The 2004 settlement was one of the largest in U.S. history up to that point, and the first off-label promotion case brought successfully under the False Claims Act.{{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 }}

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).{{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 }}{{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 }}{{cite news |title = Pfizer Told to Pay $142.1 Million for Neurontin Marketing Fraud | vauthors = Van Voris B, Lawrence J |url = https://www.bloomberg.com/apps/news?pid=email_en&sid=a_9aVylZQGjU |website = Bloomberg News |date = 26 March 2010 |access-date = 13 January 2012 |url-status=dead |archive-url = https://web.archive.org/web/20130513232138/http://www.bloomberg.com/apps/news?pid=email_en&sid=a_9aVylZQGjU |archive-date = 13 May 2013 }} In 2010, a federal jury in Massachusetts ruled in Kaiser's favor, finding that Pfizer violated the federal Racketeer Influenced and Corrupt Organizations (RICO) Act and was liable for {{US$|47.36 million}} in damages, which was automatically trebled to just under $142.1 million. Aetna, Inc. and a group of employer health plans prevailed in their similar Neurontin-related claims against Pfizer.{{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}} Pfizer appealed, but the U.S. Court of Appeals for the First Circuit upheld the verdict, and in 2013, the US Supreme Court declined to hear the case.{{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}}{{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}}

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 dependence on alcohol or cocaine. It was marketed as PROMETA. While the individual drugs had been approved by the FDA, their off-label use for addiction treatment has not.{{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 }} 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.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.{{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}}{{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}}{{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 }} Hythiam charges up to $15,000 per patient to license its use (of which half goes to the prescribing physician, and half to Hythiam).{{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 }}

In a November 2005 article entitled "Curb Your Cravings For This Stock", Barrons wrote: "If the venture works out for patients and the investing public, it'll be a rare success for Peizer, who's promoted a series of disappointing small-cap medical or technology stocks ... since his days at Drexel".{{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}} 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.{{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 }}{{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}}{{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}} 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."{{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}} Journalist Adam Feuerstein opined: "most of what Peizer says is dubious-sounding hype".{{cite web | vauthors = 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 }}

In November 2011, the results of a double-blind, placebo-controlled study (financed by Hythiam and carried out at UCLA) were published in the peer-reviewed 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."{{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 }}

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.{{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 }}

Gabapentin was originally marketed under the brand name Neurontin. Since it became generic, it has been marketed worldwide using over 300 different brand names.{{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 }} An extended-release formulation of gabapentin for once-daily administration was introduced in 2011, for postherpetic neuralgia under the brand name Gralise.{{cite web | title = Gralise Approval History | url = https://www.drugs.com/history/gralise.html | publisher = Drugs.com }}

In the US, Neurontin is marketed by Viatris after Upjohn was spun off from Pfizer.{{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}}{{cite web | title=Neurontin | website=Pfizer | url=https://www.pfizer.com/products/product-detail/neurontin | access-date=17 June 2024}}{{cite web | title=Brands | website=Viatris | date=16 November 2020 | url=https://www.viatris.com/en/products/brands | access-date=17 June 2024}}

Parke-Davis developed a drug called pregabalin, which is related in structure to gabapentin, as a successor to gabapentin.{{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 }} Another similar drug atagabalin has been unsuccessfully tried by Pfizer as a treatment for insomnia.{{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 }} A prodrug form (gabapentin enacarbil){{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 }} was approved by the U.S. Food and Drug Administration (FDA).

{{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.{{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 }}{{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 }}{{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 }} Also known on the streets as "Gabbies",{{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}} gabapentin was reported in 2017 to be increasingly abused and misused for these euphoric effects.{{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 }}{{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 }} 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.{{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 }} Gabapentin misuse, toxicity, and use in suicide attempts among adults in the US increased from 2013 to 2017.{{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 }}

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.{{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 }}

Withdrawal symptoms, often resembling those of benzodiazepine withdrawal, play a role in the physical dependence some users experience. Its misuse predominantly coincides with the usage of other CNS depressant drugs, namely opioids, benzodiazepines, and alcohol.{{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 }}

In cats, gabapentin can be used as an analgesic in multi-modal pain management,{{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 }} anxiety medication to reduce stress during travel or vet visits,{{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 }} and anticonvulsant.{{cite web |title=Gabapentin |url=https://www.plumbsveterinarydrugs.com/#!/veterinarymedicationguides |website=Plumb's Veterinary Drugs |access-date=2 April 2021}}

Veterinarians may prescribe gabapentin as an anticonvulsant and pain reliever in dogs. It has beneficial effects for treating epilepsy, different kinds of pain (chronic, neuropathic, and post-operative pain), and anxiety, lip-licking behaviour, storm phobia, fear-based aggression.{{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 }}{{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 }}

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.{{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 }}

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