Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease

Michael Raymond Binder

doi:doi:10.11648/j.ajcem.20210904.15

| Peer-Reviewed

Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease

Michael Raymond Binder

Published in American Journal of Clinical and Experimental Medicine (Volume 9, Issue 4)

Received: 13 August 2021 Accepted: 24 August 2021 Published: 31 August 2021

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Abstract

Originally marketed under the brand name Neurontin, the anticonvulsant drug gabapentin has become one of the most widely prescribed—and one of the most controversial—drugs in America. On the market for nearly three decades, the drug has been prescribed for everything from chronic cough to chronic pain and hot flashes to bipolar disorder; but is it the real deal, or is it just the brain-child of aggressive marketing, false advertising, and wishful thinking? This critical review will dissect gabapentin down to its molecular roots and trace its wide-ranging effects to better understand the drug and the persons who use it. It will also discuss how gabapentin (and other anticonvulsant drugs) may be doing something more profound than just treating acute symptoms. An emerging hypothesis contends that psychiatric and related function symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain and that the same abnormality may, over time, be driving the development of a plethora of general medical conditions, including diabetes, high blood pressure, cardiovascular disease, autoimmune diseases, dementia, and cancer. Emerging evidence suggests that the underlying physiological abnormality—an inherent hyperexcitability of the neurological system—is very common, and clinical correlation suggests that it is inherited in a classic autosomal dominant distribution. There is also evidence that the abnormality may be reflected in one’s resting vital signs, an observation that could help carriers identify the trait themselves. Gabapentin, together with other pharmacological (and non-pharmacological) interventions that reduce neuronal excitability, may, in addition to their immediate effects, have the potential to prevent the long-term erosive effects of neuronal hyperexcitability by simply turning down the stress response. Recognition of this could usher in history’s greatest campaign in the fight against sickness and disease.

Published in	American Journal of Clinical and Experimental Medicine (Volume 9, Issue 4)
DOI	10.11648/j.ajcem.20210904.15
Page(s)	122-134
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Gabapentin, Anticonvulsants, Neuronal Hyperexcitability, Genetics of Psychiatric Disorders, Ionchannelopathies, Biomarkers of Disease, Preventive Health Strategies

References

[1]	Goodman CW, Brett AS. Gabapentin and pregabalin for pain — Is increased prescribing a cause for concern? N Engl J Med 2017; (377): 411-414.
[2]	Pauly NJ, Delcher C, Slavova S, et al. Trends in gabapentin prescribing in a commercially insured U.S. adult population, 2009-2016. J Manag Care Spec Pharm 2020; 26 (3): 246-252.
[3]	GoodRx: Top 10 prescription drugs in the U.S., Published August 2020.
[4]	Mikulic M. Number of gabapentin prescriptions in the U.S. from 2004 to 2018. Statista 2021.
[5]	Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. Br J Gen Pract 2012; 62 (601): 406–407.
[6]	Gentry JR, Hill C, Malcolm R. New anticonvulsants: a review of applications for the management of substance abuse disorders. Ann Clin Psychiatry 2002; 14 (4): 233-245.
[7]	Yasaei R, Katta S, Saadabadi A. Gabapentin. StatPearls Publishing 2021.
[8]	Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med 2006; 166 (9): 1021-1026.
[9]	Chadwick D, Leiderman DB, Sauermann W, Alexander J, Garofalo E. Gabapentin in generalized seizures. Epilepsy Res 1996; (3): 191-197.
[10]	Wiffen PJ, Derry S, Bell RF, Rice AS, Tölle TR, Phillips T, Moore RA. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017; 6 (6): CD007938.
[11]	Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients. Neurology 1998; (2): 611-614.
[12]	van de Vusse AC, Stomp-van den Berg SGM, Kessels AHF, Weber WEJ. Randomised controlled trial of gabapentin in complex regional pain syndrome type 1 [ISRCTN84121379] BMC Neurol 2004; 4: 13.
[13]	Paradowski B, Bilinska M. Gabapentyna w leczeniu bólowej neuropatii w przebiegu cukrzycy typu 2 [Gabapentin in the treatment of neuropathic pain in patients with type 2 diabetes mellitus]. Pol Merkur Lekarski 2003; (85): 61-64.
[14]	Peng PWH, Wijeysundera DN, Li CCF. Use of gabapentin for perioperative pain control – A meta-analysis. Pain Res Manag 2007; 12 (2): 85–92.
[15]	Perloff MD, Berlin RK, Gillette M, Petersile MJ, Kurowski D. Gabapentin in headache disorders: What is the evidence? Pain Medicine 2016; 17 (1): 162–171.
[16]	Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001; 41 (2): 119-128.
[17]	Arnold LM, Goldenberg DL, Stanford SB, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum 2007; 56 (4): 1336-1344.
[18]	Lee KJ, Kim JH, Cho SW. Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2005; 22 (10): 981-988.
[19]	Yasmin S, Carpenter LL, Leon Z, Siniscalchi JM, Price LH. Adjunctive gabapentin in treatment-resistant depression: a retrospective chart review. J Affect Disord 2001; 63 (1-3): 243-247.
[20]	Sokolski KN, Green C, Maris DE, DeMet EM. Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology. Ann Clin Psychiatry 1999; 11 (4): 217-222.
[21]	Singh L, Field MJ, Ferris P, et al. The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine. Psychopharmacology (Berl) 1996; 127 (1): 1-9.
[22]	Markota M, Morgan RJ. Treatment of generalized anxiety disorder with gabapentin. Case Rep Psychiatry 2017; 2017: 6045017.
[23]	Pande AC, Pollack MH, Crockatt J, et al. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol 2000; 20 (4): 467-471.
[24]	Pande AC, Davidson JR, Jefferson JW, et al. Treatment of social phobia with gabapentin: a placebo-controlled study. J Clin Psychopharmacol 1999; 19 (4): 341-348.
[25]	Hamner MB, Brodrick PS, Labbate LA. Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy. Ann Clin Psychiatry 2001; 13 (3): 141-146.
[26]	Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med 2014; 174 (1): 70-77.
[27]	Myrick H et al. A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res 2009; 33: 1582.
[28]	Salehi M, Kheirabadi GR, Maracy MR, Ranjkesh M. Importance of gabapentin dose in treatment of opioid withdrawal. J Clin Psychopharmacol 2011; 31 (5): 593-596.
[29]	Sanders NC, Mancino MJ, Gentry WB, et al. Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure. Exp Clin Psychopharmacol 2013; 21 (4): 294-302.
[30]	Mariani JJ, Malcolm RJ, Mamczur AK, et al. Pilot trial of gabapentin for the treatment of benzodiazepine abuse or dependence in methadone maintenance patients. Am J Drug Alcohol Abuse 2016; 42 (3): 333-340.
[31]	Mason BJ, Crean R, Goodell V, et al. A proof-of-concept randomized controlled study of gabapentin: Effects on cannabis use, withdrawal, and executive function deficits in cannabis-dependent adults. Neuropsychopharmacology 2012; 37 (7): 1689–1698.
[32]	Sherman BJ, McRae-Clark AL. Treatment of cannabis use disorder: Current science and future outlook. Pharmacotherapy 2016; 36 (5): 511-535.
[33]	Bisaga A, Aharonovich E, Garawi F, et al. A randomized placebo-controlled trial of gabapentin for cocaine dependence. Drug Alcohol Depend 2006; 28; 81 (3): 267-274.
[34]	Myrick H, Henderson S, Brady KT, Malcolm R. Gabapentin in the treatment of cocaine dependence: a case series. J Clin Psychiatry 2001; 62 (1): 19-23.
[35]	Urschel HC 3rd, Hanselka LL, Gromov I, White L, Baron M. Open-label study of a proprietary treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in methamphetamine dependence. Mayo Clin Proc 2007; 82 (10): 1170-1178.
[36]	Allameh Z, Rouholamin S, Valaie S. Comparison of gabapentin with estrogen for treatment of hot flashes in post-menopausal women. J Res Pharm Pract 2013; 2 (2): 64–69.
[37]	Gironell A, Kulisevsky J, Barbanoj M, et al. A randomized placebo-controlled Comparative Trial of Gabapentin and Propranolol in Essential Tremor. Arch Neurol 1999; 56 (4): 475-480.
[38]	Guttuso T Jr. Gabapentin's anti-nausea and anti-emetic effects: a review. Exp Brain Res. 2014; 232 (8): 2535-2539.
[39]	Hansen HC. Interstitial cystitis and the potential role of gabapentin. South Med J 2000; 93 (2): 238-242.
[40]	Antonio C, Giovanni P, Conte A, et al. Gabapentin treatment of neurogenic overactive bladder. Clin Neuropharmacology 2006; 29 (4): 206-214.
[41]	Rayner H, Baharani J, Smith S, Suresh V, Dasgupta I. Uraemic pruritis: Relief of itching by gabapentin and pregabalin. Nephron Clin Pract 2012; 122: 75-79.
[42]	Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomized, double-blind, placebo-controlled trial. Lancet 2012; 380 (9853): 1583-1589.
[43]	Menon M. Gabapentin in the treatment of persistent hiccups in advanced malignancy. Indian J Palliat Care 2012; 18 (2): 138–140.
[44]	Taylor CP, Gee NS, Su TZ, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res. 1998; 29 (3): 233-249.
[45]	Fink K, Meder W, Dewey DJ, Gothert M. Inhibition of neuronal Ca (2+) influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. British Journal of Pharmacology 2000; 130: 900-906.
[46]	Catterall WA. Calcium Channels. In: Encyclopedia of neuroscience, 2009. Squire LR, Editor-in-Chief. pp. 543-550.
[47]	Dong L, Crosby ND, Winkelstein BA. Gabapentin alleviates facet-mediated pain in the rat through reduced neuronal hyperexcitability and astrocyte activation in the spinal cord. Journal of Pain 2013; 14 (12): 1564-1572.
[48]	Sills GJ. Mechanism of action of gabapentin and pregabalin. Current Opinions in Pharmacology 2006; 6 (1): 108-113.
[49]	Brainstorm Consortium; Anttila V, Bulik-Sullivan B, Finucane HK, et al. Analysis of shared heritability in common disorders of the brain. Science 2018; 360 (6395): eaap8757.
[50]	Uher R, Zwicker A. Etiology in psychiatry: embracing the reality of poly-gene-environmental causation of mental illness. World Psychiatry 2017; 16 (2).
[51]	Ferreira, MAR, O’Donovan MC, [...], Sklar P. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40 (9): 1056-1058.
[52]	Green EK, Grozeva D, Jones I, et al. Wellcome Trust Case Control Consortium, Holmans, PA, Owen, MJ, O'Donovan, MC, Craddock N. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 2010; 15 (10): 1016-1022.
[53]	Nieratschker V, Brückmann C, Plewnia C. CACNA1C risk variant affects facial emotion recognition in healthy individuals. Sci Rep 2015; 5: 17349.
[54]	Liu Y, Blackwood DH, Caesar S, et al. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol Psychiatry 2011; 16 (1).
[55]	Iqbal Z, Vandeweyer G, van der Voet M, et al. Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders. Human Molecular Genetics 2013; 22: 1960-1970.
[56]	Santos M, D'Amico D, Spadoni O, et al. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse model. Journal of Neuroscience 2013; 33 (38): 15259-15271.
[57]	Contractor A, Klyachko VA, Portera-Cailliau C. Altered neuronal and circuit excitability in Fragile X syndrome. Neuron 2015; 87 (4): 699-715.
[58]	O’Brien NL, Way MJ, Kandaswamy R, et al. The functional GRM3 Kozak sequence variant rs148754219 affects the risk of schizophrenia and alcohol dependence as well as bipolar disorder. Psychiatric Genetics 2014; 24: 277–278.
[59]	Schizophrenia Working Group of the Psychiatric Genomics Consortium: Ripke S, Neale BM, [...], O’Donovan MC. Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014; 511 (7510): 421-427.
[60]	Freedman R, Coon H, Myles-Worsley M, et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. PNAS 1997; 94 (2): 587–592.
[61]	Andrade A, Brennecke A, Mallat S, et al. Genetic associations between voltage-gated calcium channels and psychiatric disorders. Int J Mol Sci 2019; 20 (14): 3537.
[62]	Kim J-B. Channelopathies. Korean J of Pediatr 2014; 57 (1): 1-18.
[63]	Brunklaus A, Ellis R, Reavey E, Semsarian C, Zuberi SM. Genotype phenotype associations across the voltage-gated sodium channel family. J Med Genet 2014; 51 (10): 650-658.
[64]	D’Agnelli S, Arendt-Nielsen L, Gerra MC, et al. Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers. Molecular Pain 2019; 15.
[65]	Bahremand A, Ziai P, Khodadad TK, et al. Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole-induced seizures in mice: Involvement of L-arginine/nitric oxide pathway. Epilepsy & Behavior 2010; 18 (3): 186-192.
[66]	Brown P, Kashiviswanath S, Huynh A, et al. Lithium therapy in comorbid temporal lobe epilepsy and cycloid psychosis. Oxf Med Case Reports 2016 (12): omw089.
[67]	Shukla S, Mukherjee S, and Decina P. Lithium in the treatment of bipolar disorders associated with epilepsy: an open study. J Clin Psychopharmacol 1988: 8 (3): 201-204.
[68]	Binder MR. FLASH Syndrome: tapping into the root of chronic illness. AJCEM 2020; 8 (6): 101-109.
[69]	Blom EH, Serlachius E, Chesney MA, Olsson EMG. Adolescent girls with emotional disorders have a lower end-tidal CO₂ and increased respiratory rate compared with healthy controls. Psychophysiology 2014; 51 (5): 412-418.
[70]	Alvares GA, Quintana DS, Hickie IB, Guastella AJ. Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis. J Psychiatry Neurosci 2016; 41 (2): 89-104.
[71]	Carney RM, Freedland KE, Veith RC. Depression, the autonomic nervous system, and coronary heart disease. Psychosom Med 2005; 67 (suppl 1): S29-S33.
[72]	Clamor A, Lincoln TM, Thayer JF, Koenig J. Resting vagal activity in schizophrenia: meta-analysis of heart rate variability as a potential endophenotype. Br J Psychiatry 2016; 208 (1): 9-16.
[73]	Erlangsen A, Andersen PK, Toender A, et al. Cause-specific life-years lost in people with mental disorders: a nationwide, register-based cohort study. The Lancet 2017.
[74]	Binder MR. The multi-circuit neuronal hyperexcitability hypothesis of psychiatric disorders. AJCEM 2019; 7 (1): 12-30.
[75]	Patorno E, Bonn RL, Wahl PM, et al. Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA 2010; 303 (14): 1401-1409.
[76]	Vollmer KO, Anhut H, Thomann P, Wagner F, Jancken D. Pharmacokinetic model and absolute bioavailability of the new anticonvulsant gabapentin. Advances in Epileptology 1989; 17: 209-211.
[77]	Grunze HCR. The effectiveness of anticonvulsants in psychiatric disorders. Dialogues Clin Neurosci 2008; 10 (1): 77-89.
[78]	Binder MR. Introducing the term “Neuroregulator” in Psychiatry. AJCEM 2019; 7 (3): 66-70.
[79]	Kahn DA, Sachs GS, Printz DJ, Carpenter D. Medication treatment of bipolar disorder 2000: A summary of the expert consensus guidelines. Journal of Psychiatric Practice 2000; 6 (4): 197-211.
[80]	Kingston REF, Marel C, Mills KL. A systematic review of the prevalence of comorbid mental health disorders in people presenting for substance use treatment in Australia. Drug Alcohol Rev 2017; 36 (4): 527-539.
[81]	Smith RV, Lofwall MR, Havens JR. Abuse and diversion of gabapentin among nonmedical prescription opioid users in Appalachian Kentucky. Am J Psychiatry 2015; 172 (5): 487-488.
[82]	Reccoppa L, Malcolm R, Ware M. Gabapentin abuse in inmates with prior history of cocaine dependence. Am J Addict 2004; 13 (3): 321-323.
[83]	Pierre JM, Shnayder I, Wirshing DA, Wirshing WC. Intranasal quetiapine abuse. Am J Psychiatry 2004; 161 (9): 1718.
[84]	Waters BM, Joshi KG. Intravenous quetiapine-cocaine use ("Q-ball"). Am J Psychiatry 2007; 164 (1): 173-174.
[85]	Pinta ER, Taylor RE. Quetiapine addiction? Am J Psychiatry 2007; 164 (1): 174-175.
[86]	Del Paggio D. Psychotropic medication abuse by inmates in correctional facilities. Mental Health Clinician 2012; 1 (8): 187–188.
[87]	Bronson J, Berzofsky M. U.S. Department of Justice Special Report: Indicators of mental health problems reported by prisoners and jail inmates, 2011-2012.
[88]	McGovern PE, Zhang J, Tang J, et al. Fermented beverages of pre- and proto-historic China. PNAS 2004; 101 (51): 17593-17598.
[89]	Cavalieri D, McGovern PE, Hartl DL, Mortimer R, Polsinelli M. Evidence for S. cerevisiae fermentation in ancient wine (PDF). Journal of Molecular Evolution 2003; 57 (Suppl 1): S226–32.
[90]	Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and epilepsy. Neurotherapeutics 2015; 12 (4): 747–768.
[91]	Karst A. Weighing the benefits and risks of medical marijuana use: A brief review. Pharmacy 2018; 6: 128.
[92]	Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. British Journal of Pharmacology 2008; 153 (2): 199–215.
[93]	Silvestro S, Mammana S, Cavalli E, Bramanti P, Amazon E. Use of cannabidiol in the treatment of epilepsy: Efficacy and security in clinical trials. Molecules 2019; 24 (8): 1459.
[94]	Du Q, Liao Q, Chen C, et al. The Role of transient receptor potential vanilloid 1 in common diseases of the digestive tract and the cardiovascular and respiratory system. Front Physiol 2019.
[95]	Arnone D. Review of the use of topiramate for treatment of psychiatric disorders. Annals of General Psychiatry 2005; 4 (5): C.
[96]	Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000; 41 (suppl 1): S3-S9.
[97]	Kramer CK, Leitão CB, Pinto LC, et al. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev 2011; 12 (5): e338-347.
[98]	Hoopes SP, Reimherr FW, Hedges DW, et al. Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures. J Clin Psychiatry 2003; 64 (11): 1335-1341.
[99]	McElroy SL, Arnold LM, Shapira NA, et al. Topiramate in the treatment of binge eating disorder associated with obesity: A randomized, placebo-controlled trial. Am J Psychiatry 2003; 160 (2): 255-261.
[100]	Shapira NA, Goldsmith TD, McElroy S: Treatment of binge disorder with topiramate: a clinical case series. J Clin Psychiatry 2000; 61: 368-372.
[101]	Sachs G, Koslow GC, Orsini C, et al. Topiramate shows efficacy in the treatment of refractory bipolar mood disorder. 22nd Congress of the Collegium of Internationale Psychopharmacologieum. Brussels, Belgium, 2000.
[102]	DelBello MP, Kowatch RA, Warner J, et al. Adjunctive topiramate treatment for paediatric bipolar disorder: a retrospective chart review. J Child Adolesc Psychopharmacol 2002; 12 (4): 323-330.
[103]	McIntyre RS: An open trial to document the safety and optimal dosing of topiramate as add-on therapy to mood stabilizers in the treatment of subjects with bipolar I or II disorder with unstable mood. American Neuropharmacology Association 2002.
[104]	McIntyre RS, Mancini DA, McCann S, et al. Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: A preliminary single blind study. Bipolar Disor 2002; 4: 207-213.
[105]	Hussain MZ, Chaudhry ZA, Hussain S: Topiramate in treatment of refractory bipolar depression. Bipolar Disord 2001; 3: 43.
[106]	Vieta E, Torrent C, Garcia-Ribas G, et al. Use of topiramate in treatment-resistant bipolar spectrum disorders. J Clin Psychopharmacol 2002; 22 (4): 431-435.
[107]	Kusumakar V, Lakshmi N, Yatham MB, O'Donovan CA, Kutcher SP: Topiramate in rapid cycling bipolar women. 152nd Annual Meeting of the American Psychiatric Association. 1999, Washington, DC.
[108]	McElroy SL, Suppes T, Keck PE, et al. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 2000; 15; 47 (12): 1025-33.
[109]	Ghaemi SN, Manwani SG, Katzow JJ, Ko JY, Goodwin FK. Topiramate treatment of bipolar spectrum disorders: a retrospective chart review. Ann Clin Psychiatry 2001; 13 (4): 185-189.
[110]	Drapalski AL, Rosse RB, Peebles RR, Schwartz BL, Marvel CL, Deutsch SI: Topiramate improves deficit symptoms in a patient with schizophrenia when added to a stable regimen of antipsychotic medication. Clinical Neuropharmacology 2001; 24 (5): 290-294.
[111]	Millson RC, Owen JA, Lorberg GW, Tackaberry L: Topiramate for refractory schizophrenia. A J Psychiatry 2002; 159 (4): 67.
[112]	Mowla A, Khajeian AM, Sahraian A, Chohedri AH, Kashkoli F. Topiramate augmentation in resistant OCD: A double-blind placebo-controlled clinical trial. CNS Spectr 2010; 15 (11): 613-617.
[113]	Berlant JL, Van Kammen DP: Open label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry 2002; 63 (1): 15-20.
[114]	Abuzzahab FS, Brown VL: Control of Tourette's syndrome with topiramate. A J Psychiatry 2001; 158 (6): 968.
[115]	Johnson BA, Ait-Daoud, Bowden CL, DiClemente C, Roache JD, Lawson K, Javors MA, MA JZ: Oral topiramate in the treatment of alcohol dependence: A randomised controlled trial. Lancet 2003; 361: 1677-85.
[116]	Siniscalchi A, Bonci AB, Mercuri NB, et al. The role of topiramate in the management of cocaine addiction: A possible therapeutic option. Curr Neuropharmacol 2015; 13 (6): 815–818.
[117]	Cassano P, Lattanzi L, Pini S, Dell'Osso L, Battistini G, Cassano GB: Topiramate for self mutilation in a patient with borderline personality disorder. Bipolar Disorders 2001; 3 (3): 161.
[118]	Gregory NS, Sluka KA. Anatomical and physiological factors contributing to chronic muscle pain. Curr Top Behav Neurosci 2014; 20: 327-348.
[119]	Mense S. Muscle pain: Mechanisms and clinical significance. tsch Arztebl Int 2008; 105 (12): 214–219.
[120]	Fleming KC and Volcheck MM. Central sensitization syndrome and the initial evaluation of a patient with fibromyalgia: a review. Rambam Maimonides Med J 2015; 6 (2): e0020.
[121]	Dantzer R. Neuroimmune Interactions: From the brain to the Immune system and vice versa. Physiol Rev 2018; 98 (1): 477–504.
[122]	Wick G, Cole R, Dietrich H, et al. Chapter 7 - The obese strain of chickens with spontaneous autoimmune thyroiditis as a model for Hashimoto disease. In: Autoimmune Disease Models: A Guide Book. Elsevier, Inc. 1994 pp 107-122.
[123]	McEwen BA. Stress, adaptation, and disease allostasis and allostatic load. Annals of the New York Academy of Sciences 1998; 840 (1): 33-44.
[124]	Narkiewicz K, van de Borne P, Montano N, et al. Sympathetic neural outflow and chemoreflex sensitivity are related to spontaneous breathing rate in normal men. Hypertension 2005; 47 (1): 51-55.
[125]	Moraes DJA, Machado BH, Paton JFR. Specific respiratory neuron types have Increased excitability that drive presympathetic neurones in neurogenic hypertension. Hypertension 2014; 63: 1309-1318.
[126]	Griner T. What's really wrong with you? A revolutionary look at how muscles affect your health. Avery Publishing. New York, NY., 1995.
[127]	Binder M. The golden Book of muscle health and restoration. Lightningsource Publishing, 2016.
[128]	Huang S-W, Wang W-T, Lin L-F, et al. Association between psychiatric disorders and osteoarthritis: a nationwide longitudinal population-based study. Medicine (Baltimore) 2016; 95 (26): e4016.
[129]	Friedman M, Rosenman R. Association of specific overt behaviour pattern with blood and cardiovascular findings. Journal of the American Medical Association 1959; 169 (12): 1286–1296.
[130]	Friedman HS and Booth-Kewley S. Personality, Type A behavior, and coronary heart disease: the role of emotional expression. Journal of Personality and Social Psychology 1987; 53 (4): 783-792.
[131]	Friedman M, Thoresen CE, Gill JJ, et al. Alteration of type A behavior and its effect on cardiac recurrences in post heart attack patients: Summary results of the recurrent coronary prevention project. American Heart Journal 1986; 112 (4): 653–665.
[132]	Cherry D, Albert M, McCaig LF. Mental health-related physician office visits by adults aged 18 and over: United States, 2012-2014. NCHS Data Brief 2018; 311.
[133]	Ricky C, Siobhan, Nawaf M. Elliot G. Factors associated with delayed diagnosis of mood and/or anxiety disorders. Health Promot Chronic Dis Prev Can. 2017; 37 (5): 137–148.
[134]	Dossett ML, Fricchione GL, Benson H. A new era for mind-body medicine. N Engl J Med 2020; 382 (15): 1390-1391.
[135]	Dusek JA, Hibberd PL, Buczynski B, et al. Stress management versus lifestyle modification on systolic hypertension and medication elimination: a randomized trial. J Altern Complement Med 2008; 14 (2): 129-138.
[136]	Bonadonna R. Meditation's impact on chronic illness. Holist Nurs Pract 2003; 17 (6): 309-319.
[137]	Dimsdale JE. Psychological stress and cardiovascular disease. J Am Coll Cardiol 2008; 51 (13): 1237-1246.
[138]	Anderson KN, Bradley AJ. Sleep disturbance in mental health problems and neurodegenerative disease. Nat Sci Sleep 2013; 5: 61-75.
[139]	Nofzinger EA. Functional neuroimaging of sleep. Semin Neurol 2005; 25 (1): 9-18.
[140]	Cappuccio FP, D'Elia L, Strazzullo P, Miller MA. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep 2010; 33 (5): 585-592.
[141]	Weissman MM, Greenwald S, Niño-Murcia G, Dement WC. The morbidity of insomnia uncomplicated by psychiatric disorders. Gen Hosp Psychiatry 1997; 19 (4): 245-50.
[142]	Vgontzas AN, Pejovic S, Zoumakis E, Lin HM, Bixler EO, Basta M, Fang J, Sarrigiannidis A, Chrousos GP. Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion. Am J Physiol Endocrinol Metab 2007.
[143]	Warburton DER, Nicol CW, Bredin SSD. Health benefits of physical activity: the evidence. CMAJ 2006; 174 (6): 801–809.
[144]	Reiner M, Niermann C, Jekauc D, Woll A. Long-term health benefits of physical activity – a systematic review of longitudinal studies. BMC Public Health 2013; 13: 813.
[145]	Anderson E, Durstine JL. Physical activity, exercise, and chronic diseases: A brief review. Sports Medicine and Health Science 2019; 1 (1): 3-10.
[146]	Kerkhofs A, Xavier AC, da Silva BS, et al. Caffeine controls glutamatergic synaptic transmission and pyramidal neuron excitability in human neocortex. Front Pharmacol 2017; 8: 899.
[147]	Magalhães R, Picó-Pérez M, Esteves M, et al. Habitual coffee drinkers display a distinct pattern of brain functional connectivity. Molecular Psychiatry 2021.
[148]	Masino, SA, Kawamura Jr, M, Wasser, CD, Pomeroy, LT, Ruskin, DN. Adenosine, ketogenic diet and epilepsy: The emerging therapeutic relationship between metabolism and brain activity. Curr. Neuropharmacol 2009; 7 (3): 257-268.
[149]	Lutas A, Yellen G. The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends Neurosci 2013; 36 (1): 32-40.
[150]	Youngson NA, Morris MJ, Ballard JWO. The mechanisms mediating the antiepileptic effects of the ketogenic diet, and potential opportunities for improvement with metabolism-altering drugs. Seizure 2017; 52: 15-19.
[151]	Zhang Y, Xu J, Zhang K, Yang W, Li B. The anticonvulsant effects of ketogenic diet on epileptic seizures and potential mechanisms. Curr Neuropharmacol. 2018; 16 (1): 66-70.

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Michael Raymond Binder. (2021). Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease. American Journal of Clinical and Experimental Medicine, 9(4), 122-134. https://doi.org/10.11648/j.ajcem.20210904.15

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Michael Raymond Binder. Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease. Am. J. Clin. Exp. Med. 2021, 9(4), 122-134. doi: 10.11648/j.ajcem.20210904.15

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Michael Raymond Binder. Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease. Am J Clin Exp Med. 2021;9(4):122-134. doi: 10.11648/j.ajcem.20210904.15

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@article{10.11648/j.ajcem.20210904.15,
  author = {Michael Raymond Binder},
  title = {Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {9},
  number = {4},
  pages = {122-134},
  doi = {10.11648/j.ajcem.20210904.15},
  url = {https://doi.org/10.11648/j.ajcem.20210904.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20210904.15},
  abstract = {Originally marketed under the brand name Neurontin, the anticonvulsant drug gabapentin has become one of the most widely prescribed—and one of the most controversial—drugs in America. On the market for nearly three decades, the drug has been prescribed for everything from chronic cough to chronic pain and hot flashes to bipolar disorder; but is it the real deal, or is it just the brain-child of aggressive marketing, false advertising, and wishful thinking? This critical review will dissect gabapentin down to its molecular roots and trace its wide-ranging effects to better understand the drug and the persons who use it. It will also discuss how gabapentin (and other anticonvulsant drugs) may be doing something more profound than just treating acute symptoms. An emerging hypothesis contends that psychiatric and related function symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain and that the same abnormality may, over time, be driving the development of a plethora of general medical conditions, including diabetes, high blood pressure, cardiovascular disease, autoimmune diseases, dementia, and cancer. Emerging evidence suggests that the underlying physiological abnormality—an inherent hyperexcitability of the neurological system—is very common, and clinical correlation suggests that it is inherited in a classic autosomal dominant distribution. There is also evidence that the abnormality may be reflected in one’s resting vital signs, an observation that could help carriers identify the trait themselves. Gabapentin, together with other pharmacological (and non-pharmacological) interventions that reduce neuronal excitability, may, in addition to their immediate effects, have the potential to prevent the long-term erosive effects of neuronal hyperexcitability by simply turning down the stress response. Recognition of this could usher in history’s greatest campaign in the fight against sickness and disease.},
 year = {2021}
}

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TY  - JOUR
T1  - Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease
AU  - Michael Raymond Binder
Y1  - 2021/08/31
PY  - 2021
N1  - https://doi.org/10.11648/j.ajcem.20210904.15
DO  - 10.11648/j.ajcem.20210904.15
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 122
EP  - 134
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20210904.15
AB  - Originally marketed under the brand name Neurontin, the anticonvulsant drug gabapentin has become one of the most widely prescribed—and one of the most controversial—drugs in America. On the market for nearly three decades, the drug has been prescribed for everything from chronic cough to chronic pain and hot flashes to bipolar disorder; but is it the real deal, or is it just the brain-child of aggressive marketing, false advertising, and wishful thinking? This critical review will dissect gabapentin down to its molecular roots and trace its wide-ranging effects to better understand the drug and the persons who use it. It will also discuss how gabapentin (and other anticonvulsant drugs) may be doing something more profound than just treating acute symptoms. An emerging hypothesis contends that psychiatric and related function symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain and that the same abnormality may, over time, be driving the development of a plethora of general medical conditions, including diabetes, high blood pressure, cardiovascular disease, autoimmune diseases, dementia, and cancer. Emerging evidence suggests that the underlying physiological abnormality—an inherent hyperexcitability of the neurological system—is very common, and clinical correlation suggests that it is inherited in a classic autosomal dominant distribution. There is also evidence that the abnormality may be reflected in one’s resting vital signs, an observation that could help carriers identify the trait themselves. Gabapentin, together with other pharmacological (and non-pharmacological) interventions that reduce neuronal excitability, may, in addition to their immediate effects, have the potential to prevent the long-term erosive effects of neuronal hyperexcitability by simply turning down the stress response. Recognition of this could usher in history’s greatest campaign in the fight against sickness and disease.
VL  - 9
IS  - 4
ER  -

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Michael Raymond Binder

North Shore University Health System, Highland Park Hospital, Highland Park, USA

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Michael Raymond Binder. (2021). Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease. American Journal of Clinical and Experimental Medicine, 9(4), 122-134. https://doi.org/10.11648/j.ajcem.20210904.15

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ACS Style

Michael Raymond Binder. Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease. Am. J. Clin. Exp. Med. 2021, 9(4), 122-134. doi: 10.11648/j.ajcem.20210904.15

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AMA Style

Michael Raymond Binder. Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease. Am J Clin Exp Med. 2021;9(4):122-134. doi: 10.11648/j.ajcem.20210904.15

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@article{10.11648/j.ajcem.20210904.15,
  author = {Michael Raymond Binder},
  title = {Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {9},
  number = {4},
  pages = {122-134},
  doi = {10.11648/j.ajcem.20210904.15},
  url = {https://doi.org/10.11648/j.ajcem.20210904.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20210904.15},
  abstract = {Originally marketed under the brand name Neurontin, the anticonvulsant drug gabapentin has become one of the most widely prescribed—and one of the most controversial—drugs in America. On the market for nearly three decades, the drug has been prescribed for everything from chronic cough to chronic pain and hot flashes to bipolar disorder; but is it the real deal, or is it just the brain-child of aggressive marketing, false advertising, and wishful thinking? This critical review will dissect gabapentin down to its molecular roots and trace its wide-ranging effects to better understand the drug and the persons who use it. It will also discuss how gabapentin (and other anticonvulsant drugs) may be doing something more profound than just treating acute symptoms. An emerging hypothesis contends that psychiatric and related function symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain and that the same abnormality may, over time, be driving the development of a plethora of general medical conditions, including diabetes, high blood pressure, cardiovascular disease, autoimmune diseases, dementia, and cancer. Emerging evidence suggests that the underlying physiological abnormality—an inherent hyperexcitability of the neurological system—is very common, and clinical correlation suggests that it is inherited in a classic autosomal dominant distribution. There is also evidence that the abnormality may be reflected in one’s resting vital signs, an observation that could help carriers identify the trait themselves. Gabapentin, together with other pharmacological (and non-pharmacological) interventions that reduce neuronal excitability, may, in addition to their immediate effects, have the potential to prevent the long-term erosive effects of neuronal hyperexcitability by simply turning down the stress response. Recognition of this could usher in history’s greatest campaign in the fight against sickness and disease.},
 year = {2021}
}

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TY  - JOUR
T1  - Gabapentin — The Popular but Controversial Anticonvulsant Drug May Be Zeroing in on the Pathophysiology of Disease
AU  - Michael Raymond Binder
Y1  - 2021/08/31
PY  - 2021
N1  - https://doi.org/10.11648/j.ajcem.20210904.15
DO  - 10.11648/j.ajcem.20210904.15
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 122
EP  - 134
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20210904.15
AB  - Originally marketed under the brand name Neurontin, the anticonvulsant drug gabapentin has become one of the most widely prescribed—and one of the most controversial—drugs in America. On the market for nearly three decades, the drug has been prescribed for everything from chronic cough to chronic pain and hot flashes to bipolar disorder; but is it the real deal, or is it just the brain-child of aggressive marketing, false advertising, and wishful thinking? This critical review will dissect gabapentin down to its molecular roots and trace its wide-ranging effects to better understand the drug and the persons who use it. It will also discuss how gabapentin (and other anticonvulsant drugs) may be doing something more profound than just treating acute symptoms. An emerging hypothesis contends that psychiatric and related function symptoms are driven by pathological hyperactivity in symptom-related circuits in the brain and that the same abnormality may, over time, be driving the development of a plethora of general medical conditions, including diabetes, high blood pressure, cardiovascular disease, autoimmune diseases, dementia, and cancer. Emerging evidence suggests that the underlying physiological abnormality—an inherent hyperexcitability of the neurological system—is very common, and clinical correlation suggests that it is inherited in a classic autosomal dominant distribution. There is also evidence that the abnormality may be reflected in one’s resting vital signs, an observation that could help carriers identify the trait themselves. Gabapentin, together with other pharmacological (and non-pharmacological) interventions that reduce neuronal excitability, may, in addition to their immediate effects, have the potential to prevent the long-term erosive effects of neuronal hyperexcitability by simply turning down the stress response. Recognition of this could usher in history’s greatest campaign in the fight against sickness and disease.
VL  - 9
IS  - 4
ER  -

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