topiramate

File:Topimax 25mg.jpg

Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant. In children, it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is most frequently prescribed for the prevention of migraines,{{cite web|title=Topamax Prescribing Information|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020505s055,020844s046lbl.pdf|website=United States Food and Drug Administration|access-date=11 April 2016|archive-date=24 April 2016|archive-url=https://web.archive.org/web/20160424132704/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020505s055,020844s046lbl.pdf|url-status=dead}} as it decreases the frequency of attacks.{{cite journal | vauthors = Linde M, Mulleners WM, Chronicle EP, McCrory DC | title = Topiramate for the prophylaxis of episodic migraine in adults | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD010610 | date = June 2013 | pmid = 23797676 | pmc = 7388931 | doi = 10.1002/14651858.CD010610 }}{{cite journal | vauthors = Ferrari A, Tiraferri I, Neri L, Sternieri E | title = Clinical pharmacology of topiramate in migraine prevention | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 7 | issue = 9 | pages = 1169–1181 | date = September 2011 | pmid = 21756204 | doi = 10.1517/17425255.2011.602067 | s2cid = 207491096 }} Topiramate is used to treat medication overuse headache and is recommended by the European Federation of Neurological Societies as one of the few medications showing effectiveness for this indication.{{cite journal | vauthors = Evers S, Jensen R | title = Treatment of medication overuse headache--guideline of the EFNS headache panel | journal = European Journal of Neurology | volume = 18 | issue = 9 | pages = 1115–1121 | date = September 2011 | pmid = 21834901 | doi = 10.1111/j.1468-1331.2011.03497.x | s2cid = 2698885 | doi-access = free }}

A 2018 review found topiramate of no use in chronic low back pain.{{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 }} Topiramate has not been shown to work as a pain medicine in diabetic neuropathy, the only neuropathic condition for which it has been adequately tested.{{cite journal | vauthors = Wiffen PJ, Derry S, Lunn MP, Moore RA | title = Topiramate for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD008314 | date = August 2013 | volume = 2013 | pmid = 23996081 | pmc = 8406931 | doi = 10.1002/14651858.CD008314.pub3 | url = http://summaries.cochrane.org/CD008314/topiramate-for-treating-neuropathic-pain-or-fibromyalgia#sthash.QswJ7Tr9.dpuf | access-date = 6 September 2013 | url-status = live | veditors = Derry S | archive-url = https://web.archive.org/web/20140331085009/http://summaries.cochrane.org/CD008314/topiramate-for-treating-neuropathic-pain-or-fibromyalgia#sthash.QswJ7Tr9.dpuf | archive-date = 31 March 2014 }}

One common off-label use for topiramate is in the treatment of bipolar disorder.{{cite journal | vauthors = Arnone D | title = Review of the use of Topiramate for treatment of psychiatric disorders | journal = Annals of General Psychiatry | volume = 4 | issue = 1 | pages = 5 | date = February 2005 | pmid = 15845141 | pmc = 1088011 | doi = 10.1186/1744-859X-4-5 | doi-access = free }}{{cite journal | vauthors = Vasudev K, Macritchie K, Geddes J, Watson S, Young A | title = Topiramate for acute affective episodes in bipolar disorder | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003384 | date = January 2006 | pmid = 16437453 | doi = 10.1002/14651858.CD003384.pub2 | veditors = Young AH }}{{cite journal | vauthors = Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR | title = Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis | journal = Lancet | volume = 378 | issue = 9799 | pages = 1306–1315 | date = October 2011 | pmid = 21851976 | doi = 10.1016/s0140-6736(11)60873-8 | s2cid = 25512763 }} A review published in 2010 suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder; however, the authors noted that this was based only on one randomized controlled trial and requires replication.{{cite journal | vauthors = Lieb K, Völlm B, Rücker G, Timmer A, Stoffers JM | title = Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials | journal = The British Journal of Psychiatry | volume = 196 | issue = 1 | pages = 4–12 | date = January 2010 | pmid = 20044651 | doi = 10.1192/bjp.bp.108.062984 | doi-access = free }}

Topiramate has been used as a treatment for alcoholism.{{cite journal | vauthors = Johnson BA, Ait-Daoud N | title = Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients | journal = Current Pharmaceutical Design | volume = 16 | issue = 19 | pages = 2103–2112 | date = 2010 | pmid = 20482511 | pmc = 3063512 | doi = 10.2174/138161210791516404 }} The U.S. Veterans Affairs and Department of Defense 2015 guidelines on substance use disorders list topiramate as a "strong for" in its recommendations for alcohol use disorder.{{Cite web|url=https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf|title=VA/DoD Clinical Practice Guideline for the management of substance use disorders|date=31 December 2015|website=healthquality.va.gov|access-date=30 August 2017|archive-date=31 August 2017|archive-url=https://web.archive.org/web/20170831041618/https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf|url-status=live}}

Other uses include treatment of obesity{{cite journal | vauthors = Verrotti A, Scaparrotta A, Agostinelli S, Di Pillo S, Chiarelli F, Grosso S | title = Topiramate-induced weight loss: a review | journal = Epilepsy Research | volume = 95 | issue = 3 | pages = 189–199 | date = August 2011 | pmid = 21684121 | doi = 10.1016/j.eplepsyres.2011.05.014 | s2cid = 30103553 }}{{cite journal | vauthors = Kramer CK, Leitão CB, Pinto LC, Canani LH, Azevedo MJ, Gross JL | title = Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials | journal = Obesity Reviews | volume = 12 | issue = 5 | pages = e338–e347 | date = May 2011 | pmid = 21438989 | doi = 10.1111/j.1467-789X.2010.00846.x | s2cid = 24358798 | doi-access = free }} and binge eating disorder,{{Cite web|title=Topiramate for Binge Eating Disorder|url=https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=ty7109|access-date=3 August 2021|website=wa.kaiserpermanente.org|archive-date=3 August 2021|archive-url=https://web.archive.org/web/20210803095925/https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=ty7109|url-status=live}} and off-setting weight gain induced by taking antipsychotic medications.{{cite journal | vauthors = Mahmood S, Booker I, Huang J, Coleman CI | title = Effect of topiramate on weight gain in patients receiving atypical antipsychotic agents | journal = Journal of Clinical Psychopharmacology | volume = 33 | issue = 1 | pages = 90–94 | date = February 2013 | pmid = 23277264 | doi = 10.1097/JCP.0b013e31827cb2b7 | s2cid = 26085987 }} In 2012, the combination of phentermine/topiramate was approved in the United States for weight loss.

People taking topiramate should be aware of the following risks:

• Avoid activities requiring mental alertness and coordination until drug effects are realized.
• Topiramate may impair heat regulation, especially in children. Use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat, or dehydration.
• Topiramate may cause visual field defects.{{cite web|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm195797.htm|title=Topamax (topiramate) tablets and sprinkle capsules|publisher=Fda.gov|access-date=17 October 2014|archive-date=12 January 2017|archive-url=https://web.archive.org/web/20170112172852/http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm195797.htm|url-status=dead}}
• Topiramate may decrease the effectiveness of oestrogen-containing oral contraceptives.
• Taking topiramate in the first trimester of pregnancy may increase the risk of cleft lip/cleft palate in infants.
• As is the case for all antiepileptic drugs, it is advisable not to suddenly discontinue topiramate, as there is a theoretical risk of rebound seizures.
• Some studies have attributed loss of appetite and upper respiratory tract infection to topiramate, but studies have concluded these adverse events are not difficult to tolerate for most individuals.{{Cite web |date=8 August 2021 |title=Seizures and Epilepsy in Children |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/epilepsy/seizures-and-epilepsy-in-children |access-date=19 July 2023 |website=www.hopkinsmedicine.org }}

Adverse effects by incidence:{{cite web|title=Topamax Tablets and Sprinkle Capsules PRODUCT INFORMATION|work=TGA eBusiness Services|publisher=JANSSEN-CILAG Pty Ltd|date=30 May 2013|access-date=18 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-02205-3|format=PDF|archive-date=29 March 2019|archive-url=https://web.archive.org/web/20190329054936/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-02205-3|url-status=live}}{{cite web|title=topiramate (Rx) - Topamax, Trokendi XR|work=Medscape Reference|publisher=WebMD|access-date=18 November 2013|url=http://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023|archive-date=19 May 2019|archive-url=https://web.archive.org/web/20190519021543/https://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023|url-status=live}}{{cite web|title=Topiramate 100 mg film-coated Tablets|work=electronic Medicines Compendium|publisher=Sandoz Limited|date=6 March 2013|access-date=18 November 2013|url=http://www.medicines.org.uk/emc/medicine/22416/SPC/Topiramate+100+mg+film-coated+Tablets/|archive-url= https://web.archive.org/web/20140521031853/http://www.medicines.org.uk/emc/medicine/22416/SPC/Topiramate+100+mg+film-coated+Tablets/ |archive-date=21 May 2014 |url-status=dead}}{{cite web|title=TOPIRAMATE ( topiramate ) tablet TOPIRAMATE ( topiramate ) tablet [Torrent Pharmaceuticals Limited]|work=DailyMed|publisher=Torrent Pharmaceuticals Limited|date=August 2011|access-date=18 November 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a4ff77b8-04bc-4edb-a085-8d6d8687f8d1|archive-date=20 May 2014|archive-url=https://web.archive.org/web/20140520220544/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a4ff77b8-04bc-4edb-a085-8d6d8687f8d1|url-status=live}}

Very common (>10% incidence) adverse effects include:

{{Columns-list|

• Dizziness
• Weight loss
• Paraesthesia – e.g., pins and needles
• Somnolence
• Nausea
• Diarrhea
• Fatigue
• Nasopharyngitis
• Depression

}}

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.{{cite journal | vauthors = Mirza N, Marson AG, Pirmohamed M | title = Effect of topiramate on acid-base balance: extent, mechanism and effects | journal = British Journal of Clinical Pharmacology | volume = 68 | issue = 5 | pages = 655–661 | date = November 2009 | pmid = 19916989 | pmc = 2791971 | doi = 10.1111/j.1365-2125.2009.03521.x }}

The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly.{{cite web|url=https://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM173936.pdf|title=IMPORTANT DRUG WARNING| vauthors = Hulihan J |date=2001|website=FDA MedWatch|publisher=Ortho-McNeil Pharmaceutical|archive-url=https://wayback.archive-it.org/7993/20170113165159/https://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM173936.pdf|archive-date=13 January 2017|url-status=dead|access-date=11 June 2018}} The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage and may reverse the visual impairment.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.{{cite journal | vauthors = Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J | title = Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register | journal = Neurology | volume = 71 | issue = 4 | pages = 272–276 | date = July 2008 | pmid = 18645165 | doi = 10.1212/01.wnl.0000318293.28278.33 | s2cid = 13562052 }} This might be particularly important for women who take topiramate to prevent migraine attacks. In March 2011, the FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in Pregnancy Category D.{{cite web |url=https://www.fda.gov/Drugs/DrugSafety/ucm245085.htm | work = FDA Drug Safety Communication | title = Risk of oral clefts in children born to mothers taking Topamax (topiramate) |publisher=Fda.gov |date=6 January 2011 |access-date=11 July 2013 |archive-date=24 April 2019 |archive-url=https://web.archive.org/web/20190424012653/https://www.fda.gov/Drugs/DrugSafety/ucm245085.htm |url-status=dead }}

Cognitive and word-finding difficulties, which may occur in some patients, may respond to piracetam.Berthier, M.L. and Dávila, G., 2023. Pharmacotherapy for post-stroke aphasia: what are the options?. Expert Opinion on Pharmacotherapy, (just-accepted).Cumbo, E. and Ligori, L.D., 2010. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease. Epilepsy & Behavior, 17(4), pp.461-466.

Carbonation dysgeusia (distortion of the sense of taste-sensation of carbonation) may respond to and/or be prevented with zinc.Charbonneau, M., Doyle-Campbell, C., Laskey, C. and Capoccia, K., 2020. Carbonation dysgeusia associated with topiramate. American Journal of Health-System Pharmacy, 77(14), pp.1113-1116.

Topiramate has been associated with a statistically significant increase in suicidality,{{cite web |url=https://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4344s1_09_01_Trileptal%20slides.pdf |title=Suicidality and Antiepileptic Drugs |website=Food and Drug Administration |access-date=11 July 2013 |archive-date=10 May 2017 |archive-url=https://web.archive.org/web/20170510065536/https://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4344s1_09_01_Trileptal |url-status=dead }} and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500."{{cite web|url=http://www.topamax.com/how-topamax-may-help--what-to-expect.html|archive-url=https://web.archive.org/web/20110128083201/http://www.topamax.com/how-topamax-may-help--what-to-expect.html|url-status=dead|archive-date=28 January 2011|title=Possible Side Effects - Topamax (topiramate)|publisher=Topamax.xom|access-date=17 October 2014}}{{cite web | title = Topiramate | url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000998/ | archive-url = https://web.archive.org/web/20100805062310/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000998/ | archive-date=5 August 2010 | work = PubMed Health | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine }}

Symptoms of acute and acute on chronic exposure to topiramate range from asymptomatic to status epilepticus, including in patients with no seizure history.{{cite journal | vauthors = Wiśniewski M, Łukasik-Głebocka M, Anand JS | title = Acute topiramate overdose--clinical manifestations | journal = Clinical Toxicology | volume = 47 | issue = 4 | pages = 317–320 | date = April 2009 | pmid = 19514879 | doi = 10.1080/15563650601117954 | s2cid = 205901501 }}{{cite journal | vauthors = Wills B, Reynolds P, Chu E, Murphy C, Cumpston K, Stromberg P, Rose R | title = Clinical outcomes in newer anticonvulsant overdose: a poison center observational study | journal = Journal of Medical Toxicology | volume = 10 | issue = 3 | pages = 254–260 | date = September 2014 | pmid = 24515527 | pmc = 4141920 | doi = 10.1007/s13181-014-0384-5 }} In children, overdose may also result in hallucinations. Topiramate has been deemed the primary substance that led to fatal overdoses in cases that were complicated by polydrug exposure.{{cite journal | vauthors = Lofton AL, Klein-Schwartz W | title = Evaluation of toxicity of topiramate exposures reported to poison centers | journal = Human & Experimental Toxicology | volume = 24 | issue = 11 | pages = 591–595 | date = November 2005 | pmid = 16323576 | doi = 10.1191/0960327105ht561oa | bibcode = 2005HETox..24..591L | s2cid = 37784043 }} The most common signs of overdose are dilated pupils, somnolence, dizziness, psychomotor agitation, and abnormal, uncoordinated body movements.

Topiramate has many drug-drug interactions. Some of the most common are listed below:

• As topiramate inhibits carbonic anhydrase, use with other inhibitors of carbonic anhydrase (e.g. acetazolamide) increases the risk of kidney stones.{{citation needed|date=April 2016}}
• Enzyme inducers (e.g. carbamazepine) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.{{citation needed|date=April 2016}}
• Topiramate may increase the plasma levels of phenytoin.
• Topiramate itself is a weak inhibitor of CYP2C19 and induces CYP3A4; a decrease in plasma levels of estrogens and digoxin has been noted during topiramate therapy. This can reduce the effectiveness of oral contraceptives (birth control pills); use of alternative birth control methods is recommended.{{cite book| veditors = Sweetman SC |chapter=Sex hormones and their modulators|title=Martindale: The complete drug reference |edition=36th |year=2009 |page=2068 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|title-link=Martindale: The complete drug reference}} Neither intrauterine devices (IUDs) nor Depo-Provera are affected by topiramate.
• Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure.
• As topiramate may result in acidosis, other treatments that also do so may worsen this effect.{{cite web | title = TOPAMAX (topiramate) Tablets Approved Labeling Text | date = 29 June 2005 | work = Ortho-McNeil Pharmaceutical | publisher = U.S. Food and Drug Administration | url = https://www.fda.gov/cder/foi/label/2005/020505s018lbl.pdf | archive-url = https://web.archive.org/web/20070205092259/https://www.fda.gov/cder/foi/label/2005/020505s018lbl.pdf | archive-date=5 February 2007 |page=14}}
• Oligohidrosis and hyperthermia were reported in post-marketing reports about topiramate; antimuscarinic drugs (like trospium) can aggravate these disorders.{{citation needed|date=April 2016}}

File:Topiramate (chair style).svg

The topiramate molecule is a sulfamate modified sugar – more specifically, fructose diacetonide, an unusual chemical structure for a pharmaceutical.

Topiramate is quickly absorbed after oral use. It has a half-life of 21 hours and a steady state of the drug is reached in 4 days in patients with normal renal function.{{Cite web|title=FDA Data on Topamax|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020505s038s039,020844s032s034lbl.pdf|url-status=dead|access-date=6 August 2021|archive-date=6 August 2021|archive-url=https://web.archive.org/web/20210806051822/https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020505s038s039,020844s032s034lbl.pdf}} Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.

Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.{{cite book |vauthors= Porter RJ, Dhir A, Macdonald RL, Rogawski MA |chapter= Mechanisms of action of antiseizure drugs |title= Handb Clin Neurol |year= 2012 |volume= 108 |pages= 663–681 |doi= 10.1016/B978-0-444-52899-5.00021-6 |pmid= 22939059 |chapter-url= http://works.bepress.com/michael_rogawski/41/ |series= Handbook of Clinical Neurology |isbn= 9780444528995 |access-date= 22 May 2014 |archive-date= 22 June 2017 |archive-url= https://web.archive.org/web/20170622140812/https://works.bepress.com/michael_rogawski/41/ |url-status= dead }} These include (1) voltage-gated sodium channels; (2) high-voltage-activated calcium channels; (3) GABA-A receptors; (4) AMPA/kainate receptors; and (5) carbonic anhydrase isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by direct action.{{cite journal | vauthors = Meldrum BS, Rogawski MA | title = Molecular targets for antiepileptic drug development | journal = Neurotherapeutics | volume = 4 | issue = 1 | pages = 18–61 | date = January 2007 | pmid = 17199015 | pmc = 1852436 | doi = 10.1016/j.nurt.2006.11.010 }} The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit high-voltage-activated calcium channels, its relevance to clinical activity is uncertain. Effects on specific GABA-A receptor isoforms could also contribute to the antiseizure activity of the drug. Topiramate selectively inhibits cytosolic (type II) and membrane-associated (type IV) forms of carbonic anhydrase. Its action on carbonic anhydrase isoenzymes may contribute to the drug's side effects, including its propensity to cause metabolic acidosis and calcium phosphate kidney stones.

Topiramate inhibits maximal seizure activity in electroconvulsive therapy and in pentylenetetrazol-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on mitochondrial permeability transition pores has been proposed as a mechanism.{{cite journal | vauthors = Kudin AP, Debska-Vielhaber G, Vielhaber S, Elger CE, Kunz WS | title = The mechanism of neuroprotection by topiramate in an animal model of epilepsy | journal = Epilepsia | volume = 45 | issue = 12 | pages = 1478–1487 | date = December 2004 | pmid = 15571505 | doi = 10.1111/j.0013-9580.2004.13504.x | s2cid = 7067509 | doi-access = free }}

While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is one of the very few anticonvulsants [see: levetiracetam, carbamazepine, lamotrigine] that do not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.{{cite journal | vauthors = Czuczwar K, Czuczwar M, Cieszczyk J, Gawlik P, Luszczki JJ, Borowicz KK, Czuczwar SJ | title = [Neuroprotective activity of antiepileptic drugs] | journal = Przeglad Lekarski | volume = 61 | issue = 11 | pages = 1268–1271 | year = 2004 | pmid = 15727029 }}

Blood, serum, or plasma topiramate concentrations may be measured using immunoassay or chromatographic methods to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, or assist in a medicolegal death investigation. Plasma levels are usually less than 10 mg/L during therapeutic administration, but can range from 10 to 150 mg/L in overdose victims.{{cite journal | vauthors = Goswami D, Kumar A, Khuroo AH, Monif T, Rab S | title = Bioanalytical LC-MS/MS method validation for plasma determination of topiramate in healthy Indian volunteers | journal = Biomedical Chromatography| volume = 23 | issue = 11 | pages = 1227–41 | date = November 2009 | pmid = 19593736 | doi = 10.1002/bmc.1273 }}{{cite journal | vauthors = Brandt C, Elsner H, Füratsch N, Hoppe M, Nieder E, Rambeck B, Ebner A, May TW | title = Topiramate overdose: a case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticus | journal = Epilepsia | volume = 51 | issue = 6 | pages = 1090–1093 | date = June 2010 | pmid = 19889015 | doi = 10.1111/j.1528-1167.2009.02395.x | s2cid = 35752877 | doi-access = }}{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1567–1569 }}

Topiramate was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceuticals.{{cite journal | vauthors = Maryanoff BE, Nortey SO, Gardocki JF, Shank RP, Dodgson SP | title = Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds | journal = Journal of Medicinal Chemistry | volume = 30 | issue = 5 | pages = 880–887 | date = May 1987 | pmid = 3572976 | doi = 10.1021/jm00388a023 }}{{cite journal | vauthors = Maryanoff BE, Costanzo MJ, Nortey SO, Greco MN, Shank RP, Schupsky JJ, Ortegon MP, Vaught JL | title = Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 8 | pages = 1315–1343 | date = April 1998 | pmid = 9548821 | doi = 10.1021/jm970790w }} Topiramate was first sold

in 1996.{{cite book| vauthors = Pitkänen A, Schwartzkroin PA, Moshé SL |title=Models of Seizures and Epilepsy |date=2005 |publisher=Elsevier |location=Burlington |isbn=9780080457024 |page=539 |url= https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539|access-date=17 September 2017|archive-date=8 September 2017|archive-url=https://web.archive.org/web/20170908192246/https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539|url-status=live}} Mylan Pharmaceuticals was granted final approval by the FDA for the sale of generic topiramate in the United States and the generic version was made available in September 2006.{{cite web | vauthors = Waknine Y | date = 22 September 2006 |url=http://www.medscape.com/viewarticle/544994 |title=First-Time Generic Approvals: Seasonale, Imodium Advanced, and Topamax |publisher=Medscape.com |access-date=11 July 2013 |archive-date=20 May 2013 |archive-url= https://web.archive.org/web/20130520134911/http://www.medscape.com/viewarticle/544994 |url-status=live }} The last patent for topiramate in the U.S. was for use in children and expired on 28 February 2009.{{cite web |url= http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020844&Product_No=002&table1=OB_Rx |title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|publisher=Accessdata.fda.gov|access-date=17 October 2014|archive-date=25 April 2016|archive-url= https://web.archive.org/web/20160425045412/http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020844&Product_No=002&table1=OB_Rx|url-status=dead}}

Topiramate is being studied as a potential treatment for post-traumatic stress disorder (PTSD).{{cite journal | vauthors = Andrus MR, Gilbert E | title = Treatment of civilian and combat-related posttraumatic stress disorder with topiramate | journal = The Annals of Pharmacotherapy | volume = 44 | issue = 11 | pages = 1810–1816 | date = November 2010 | pmid = 20923947 | doi = 10.1345/aph.1P163 | s2cid = 12137726 }}

There is some evidence for the use of topiramate in the management of cravings related to withdrawal from dextromethorphan.{{cite journal | vauthors = Roy AK, Hsieh C, Crapanzano K | title = Dextromethorphan Addiction Mediated Through the NMDA System: Common Pathways With Alcohol? | journal = Journal of Addiction Medicine | volume = 9 | issue = 6 | pages = 499–501 | date = 2015 | pmid = 26441400 | doi = 10.1097/ADM.0000000000000152 }}

A 2023 systematic review of seizure treatment for infants aged 1 to 36 months identified three studies that evaluated the use of topiramate. Though its adverse effects, including upper respiratory tract infection and loss of appetite, were rarely severe enough for the medication to be discontinued in this age group, its effectiveness in reducing seizures was inconclusive. The available research suffers from small sample sizes, inconsistent findings, and inadequate comparison groups.{{Cite report | vauthors = Treadwell JR, Wu M, Tsou AY |date=25 October 2022 |title=Management of Infantile Epilepsies |doi=10.23970/ahrqepccer252 | doi-access= | title-link=doi | publisher=Agency for Healthcare Research and Quality }}

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