IUPAC_name = 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate

width = 191
CAS_number = 97240-79-4
ATC_prefix = N03
ATC_suffix = AX11
ATC_supplemental =
PubChem = 5284627
DrugBank = APRD00237
C = 12 | H = 21 | N = 1 | O = 8 | S = 1
molecular_weight = 339.363 g/mol
smiles = NS(=O)(=O)OC [C@@] 13OC(C)(C)O [C@H] 3C2OC(C)(C)OC2CO1
bioavailability = 80%
protein_bound =
metabolism = 30% hepatic, 70% is excreted unchanged
elimination_half-life = 19 to 23 hours
pregnancy_AU =
pregnancy_US = C
legal_UK = POM
legal_US = Rx-only
routes_of_administration = Oral
excretion = 70% renal (in urine) in unchanged form

Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics and Noramco, Inc., both being divisions of Johnson & Johnson. Generic versions are available in Canada and were FDA approved in September 2006 . Mylan Pharmaceuticals was recently granted final approval for generic topiramate 25, 100, and 200 mg tablets and sprinkle capsules by the FDA for sale in the US. 50 mg tablets were granted tentative approval. [] It was discovered in 1979 by Drs. Bruce E. Maryanoff and Joseph F. Gardocki during their research work in McNeil Pharmaceutical. [B. E. Maryanoff, S. O. Nortey, J. F. Gardocki, R. P. Shank, and S. P. Dodgson, "Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds", J. Med. Chem., 30, 880-887 (1987)] [B. E. Maryanoff, M. J. Costanzo, S. O. Nortey, M. N. Greco, R. P. Shank, J. J. Schupsky, M. E. Ortegon, and J. L. Vaught, "Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives", J. Med. Chem., 41, 1315-1343 (1998)] [B. E. Maryanoff and J. F. Gardocki, "Anticonvulsant sulfamate derivatives", U.S. Patent 4,513,006 (1985)]


This drug is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delay). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, [Kusumakar, V.;Lakshmi, N.;Yatham, MB.;O'Donovan, CA.; Kutcher, SP. 152nd Annual Meeting of the American Psychiatric Association. Washington, DC; 1999. Topiramate in rapid cycling bipolar women.] [Marcotte D. Longer term treatment with topiramate for bipolar disorders. Bipolar Disord. 2001;3:46.] [Sachs, G.;Koslow, GC.;Orsini, C.;Cosgrove, V.;Sambur, M.;Demopulos, C.; Ghaemi, S. Topiramate shows efficacy in the treatment of refractory bipolar mood disorder. 22nd Congress of the Collegium of Internationale Psychopharmacologieum. Brussels, Belgium. 2000.] although it is not FDA approved for this purpose. This drug has been investigated for use in treatment of obesity, [Van Ameringen M, Mancini C, Pipe B, Campbell M, Oakman J. Topiramate treatment for SSRI-induced weight gain in anxiety disorders. J Clin Psychiatry. 2002;63:981-984.] [Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M; OBES-002 Study Group. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes Relat Metab Disord. 2004 Nov;28(11):1399-410.] especially to aid in the reduction of binge eating, [Shapira NA, Goldsmith TD, McElroy S. Treatment of binge disorder with topiramate: a clinical case series. J Clin Psychiatry. 2000;61:368-372.] [McElroy SL, Arnold LM, Shapira NA, Keck PE, Rosenthal NR, Rezaul Karim M, Kamin M, Hudson JI. Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160:255-261.] and also as a possible treatment for alcoholism. [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.] cite journal |author=Johnson BA, Rosenthal N, Capece JA, "et al" |title=Topiramate for treating alcohol dependence: a randomized controlled trial |journal=JAMA |volume=298 |issue=14 |pages=1641–51 |year=2007 |month=October |pmid=17925516 |doi=10.1001/jama.298.14.1641 |url=] However, these uses are not actively promoted by the manufacturer, and like its use for bipolar disorder, are off-label uses.

The drug is also used in clinical trials to treat Post Traumatic Stress Disorder. [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;63:15-20.] A pilot study suggests that Topiramate is possibly effective against infantile spasms. [Glauser TA, Clark PO, Strawsburg R. A pilot study of topiramate in the treatment of infantile spasms. Epilepsia. 1998 Dec;39(12):1324-8.] A study by Harvard recommends topiramate as an effective treatment in the prevention of Periventricular leukomalacia in preterm infants after an hypoxic-ischemic injury. [Follett PL, Deng W, Dai W, Talos DM, Massillon LJ, Rosenberg PA, Volpe JJ, Jensen FE. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J Neurosci. 2004 May 5;24(18):4412-20. PMID 15128855] In May 2006 the U.S. National Institutes of Health web site listed several studies sponsored by Ortho-McNeil which propose to examine the use of topiramate on migraine, cluster, [La'inez MJ, Pascual J, Pascual AM, Santonja JM, Ponz A, Salvador A. Topiramate in the prophylactic treatment of cluster headache. Headache. 2003 Jul-Aug;43(7):784-9.] and severe headaches within various demographics. Other off-label and investigational uses of topiramate include: treatment of bulimia nervosa, [Hoopes SP, Reimherr FW, Hedges DW, Rosenthal NR, Kamin M, Karim R, Capece JA, Karvois D. 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;64:1335-41.] obsessive-compulsive disorder, treatment of alcoholism, [ [ Study: Migraine pill helps some alcoholics taper off - ] ] smoking cessation, [Khazaal Y, Cornuz J, Bilancioni R, Zullino DF. Topiramate for smoking cessation. Psychiatry Clin Neurosci. 2006 Jun;60(3):384-8.] Pseudotumor Cerebri, and treatment of neuropathic pain. [Chong MS, Libretto SE. The rationale and use of topiramate for treating neuropathic pain. Clin J Pain. 2003 Jan-Feb;19(1):59-68.]


Chemically, topiramate is a sulfamate-substituted monosaccharide, related to fructose, a rather unusual chemical structure for an anticonvulsant.

Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine as unchanged drug. 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.

Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particularly subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and 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 |author=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=1478–87 |year=2004 |month=December |pmid=15571505 |doi=10.1111/j.0013-9580.2004.13504.x |url=]

It also is a sodium channel blocker.cite web |url= |title=Topiramate in the Treatment of Sciatica - Full Text View - |format= |work= |accessdate=]

ide effects

A GlaxoSmithKline-sponsored Phase IV (post-marketing) study suggested that cognitive side effects may be more common with topiramate than with lamotrigine. [cite journal
author=Blum D, Meador K, Biton V, "et al"
title=Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy
] In studies of healthy volunteers, comparing the two medications, therapeutic doses of topiramate for bipolar disorder produced greater cognitive deficits than lamotrigine, including short term memory loss and word-finding difficulty. This effect has led to the occasional use of the name "dopamax" by some dissatisfied customers. A flat affect was reported in > 75% patients (n=60).Fact|date=May 2007

The Following side effects have been seen during clinical trials of topamax in preventing frequently recurring migrainnes: The most often reported effects were: tiredness, pins and needles in the fingers and toes, dizziness, lowered sense of feeling in the skin, difficulty with language, nausea, diarrhoea, indigestion, dry mouth, weight lost, decrease in appetite, drowsiness, forgetfulness, difficulty with concentration or attention, difficulty in sleeping (insomnia), anxiety, mood swings, depression, changes in taste and vision disorders.

General: Rarely, blood clots have occurred in patients given topamax. However, it has not been proven that these were caused by this medicine. Rarely, blurring of vision and eye pain have been reported. Rarely and mostly in children, reduced sweating has occurred, mainly during exercise or in warm conditions. If someone taking Topamax becomes flushed or overheated, they should relax in a cool place and drink plenty of water. Very rarely, drug withdrawal convulsions (fits) have been reported.

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.

The side-effects most frequently leading to discontinuation of therapy with topiramate were:
* Psychomotor slowing (4.1%)
* Memory problems (3.3%)
* Fatigue (3.3%)
* Confusion (3.2%)
* Somnolence (3.2%)

The side-effects reported by > 10% of subjects in at least 1 clinical study [cite journal
last = Chengappa
first = K. N. Roy
authorlink =
coauthors = LK Schwarzman, JF Hulihan, J Xiang, NR Rosenthal
title = Adjunctive Topiramate Therapy in Patients Receiving a Mood Stabilizer fo Bipolar I Disorder: A Randomized Placebo-Controlled Trial
journal = J Clin Psychiatry
volume = 67
issue = 11
pages = 1703
publisher = Physicians Postgraduate Press
month = November | year = 2006
url =
doi =
id = ISSN 0160-6689
accessdate =
] Listed by prevalence:(*indicates placebo rate [%] is the same or higher than side-effect rate)
* headache (23.8%) * [25.9%]
* paresthesia (numbness & tingling) (23.1%)
* upper respiratory tract infection (17.5%)
* diarrhea (16.8%)
* nausea (15.4%)
* somnolence (15.4%) * [16.1%]
* anorexia (loss of appetite) (13.3%) * [5.6%]
* insomnia (11.9%) * [11.2%]
* memory problems (11.2%)
* dizziness (10.5%) * [10.5]

The Food and Drug Administration (FDA) has issued a notification alerting physicians who prescribe topiramate, and their patients, to the risk of vision loss (blindness). Acute myopia and secondary angle closure glaucoma, in a small subset of patients who take topiramate regularly, may cause transient (reversible), or permanent, loss of vision. The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. If addressed early in its course, discontinuation of topiramate, along with other measures deemed prudent by the prescribing physician and/or ophthalmologist, may halt the progression of the ocular damage, and may reverse the visual impairment. Patients who take topiramate and who feel pain in or around their eyes, or notice a loss of vision, visual acuity, or blurred vision, are advised to seek consultation with their physician as soon as reasonably possible. According to the FDA: "in more than 825,000 patients...As of August 17, 2001 there have been 23 reported cases: 22 in adults and 1 in pediatric patients. It is generally recognized that postmarketing data are subject to substantial under-reporting."

Another serious side-effect is the development of osteoporosis in adults and children (bones affected break more easily) and rickets (abnormal, deformed growth of bones) in children. Topiramate may also slow the growth of children. All of these conditions should be detected early by performing regular clinical examinations of the patients.

In other postmarketing research, a risk of decreased sweating and hyperthermia was discovered. Pediatric patients (children) are especially prone to this side-effect. It is recommended that children treated with topiramate should be monitored closely for evidence of decreased sweating and increased body temperature, especially in hot weather. All patients, particularly those with other predisposing factors, should be instructed to maintain an adequate fluid intake in order to minimize the risk of kidney stone formation.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.cite journal |author=Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J |title=Preliminary experience from the UK Epilepsy and Pregnancy Register |journal=Neurology |volume=71 |issue=4 |pages=272-276 |year=2008 |pmid=18645165 |doi= |url=] This might be particularly important for women who take topiramate to prevent migraine attacks.


* As topiramate inhibits carbonic anhydrase, the concomitant use of other inhibitors of carbonic anhydrase (e.g. acetazolamide) may lead to an increased risk of renal stones.
* Enzyme inductors (e.g. carbamazepine): The elimination of topiramate may be increased, possibly requiring dose escalations of topiramate.
* Phenytoin: Topiramate may increase the plasma-levels of phenytoin.
* Topiramate itself is a weak inhibitor of CYP2C19 and induces CYP3A4. Under topiramate a decrease of plasma-levels of estrogens (e.g. 'the pill') and digoxin have been noted.
* Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure.
* As listed in the 06/29/2005 label posted at the Drugs@FDA website page 14,'conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of Topiramate'. Absent from this label is any direct discussion of narcotic (drugs known to promote respiratory acidosis) interactions. This discussion on page 14 is under the topic of Metabolic Acidosis, and is not repeated under the topic of interactions. [ [S] ]
* Oligohydrosis and hyperthermia were reported in post-marketing reports about topiramate, antimuscarinic drugs (like trospium) can aggravate these disorders.


In order to avoid early side-effects (e.g. cognitive dysfunction) the initial dosage normally is low and increased in slow steps. The usual initial dosage is 25 to 50 mg daily in 2 single doses. Recommended increments are 25 to 50mg every 1 or 2 weeks. Common dosages for maintenance treatment are 100 to 200 mg daily. The highest dosage possible is 1,000 mg daily in divided doses.


Symptoms of overdose may include but are not limited to:

* Seizures
* Dizziness, drowsiness, tiredness
* Agitation
* Depression
* Speech problems
* Blurred vision, double vision
* Troubled thinking
* Loss of coordination
* Inability to respond to things around you
* Loss of consciousness
* Confusion and coma
* Fainting
* Upset stomach and stomach pain
* Loss of appetite and vomiting
* Excessive hunger
* Shortness of breath; fast, shallow breathing
* Pounding or irregular heartbeat
* Muscle weakness
* Bone pain

A specific antidote is not available. Treatment is entirely symptomatic.


External links

* [ Topamax (topiramate): Treatment for Migraine Prevention]
* [ Topamax (topiramate): Break the Migraine Cycle; the FDA and Topamax (topiramate) as a psychotherapeutic agent in Bipolar Disorder.]
* [ Topamax: Treatment for Epilepsy]
* [ Currently listed clinical trials related to topiramate]
* [ FDA topiramate safety]
* [ MSN article]
* [ Effects of topiramate]
* [ Patient oriented article on Topiramate from a neurologist]
* [ MedlinePlus: Topiramate]
* [ FAQ: Topiramate (Topamax), Mood Disorders and PTSD]
* [ Topiramate]
* [ Focus on Topiramate - a new anti-epileptic] , Ben Green, Priory Lodge Education Ltd., 1997-99. Version 1.1

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Topiramate — Général Nom IUPAC sulfamate de [(3aS,5aR,8aR,8bS) 2,2,7,7 tétraméthyltétrahydro 3aH bis[1,3]dioxolo[4,5 b:4 ,5 d]pyran 3a yl]méthyle …   Wikipédia en Français

  • topiramate — noun An anticonvulsant drug used in the treatment of epilepsy …   Wiktionary

  • topiramate — n. see anticonvulsant * * * to·pi·ra·mate (to piґrə māt) a substituted monosaccharide used as an anticonvulsant in the treatment of partial seizures; administered orally …   Medical dictionary

  • topiramate — n.; see anticonvulsant …   The new mediacal dictionary

  • 97240-79-4 — Topiramate Topiramate Général No CAS …   Wikipédia en Français

  • C12H21NO8S — Topiramate Topiramate Général No CAS …   Wikipédia en Français

  • Topiramato — Nombre (IUPAC) sistemático …   Wikipedia Español

  • Топирамат — …   Википедия

  • Alcoholism — Classification and external resources …   Wikipedia

  • Mood stabilizer — A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, typically bipolar disorder. Contents 1 Uses 2 Examples 2.1 Anticonvulsants 2.2 …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.