Topiramate

Definition

Topiramate is an anticonvulsant indicated for the control of seizures in the treatment of epilepsy (a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain) and Lennox-Gastaut syndrome (a disorder which causes seizures and developmental delays).

In psychiatry, topiramate may also be used in the treatment of bipolar affective disorders.

Purpose

Topiramate is thought to decrease and balance the abnormal electrical activity within the brain that may trigger seizures. While topiramate controls some types of seizures associated with epilepsy, there is no known cure for the disorder.

In patients with bipolar disorders, topiramate stabilizes mood without producing a euphoric feeling or inducing manic episodes.

Description

In the United States, topiramate is sold under the brand name Topamax.

Topiramate is most commonly prescribed to treat patients who do not respond to other anticonvulsant medications, or is part of a combination of anticonvulsant medications used to treat intractable seizures. Although the precise mechanisms by which it exerts its therapeutic effects in epilepsy and other seizure disorders are unknown, topiramate has three specific seizure-reducing actions:

• topiramate decreases nerve-cell excitation by blocking targeted neurotransmitters from binding to certain receptors in the brain.
• topiramate blocks sodium channels in nerve cells, thus decreasing excessive nerve-cell firing.
• topiramate increases the availability of GABA, (gammaaminobutyric acid), a neurotransmitter that inhibits nerve-cell excitation in the brain.

Recommended dosage

Topiramate is taken by mouth in tablet or sprinkle form. Topiramate is available in strengths of 25 mg, 100 mg, and 200 mg tablets, along with 15 mg and 25 mg sprinkle capsules. Patients usually take topiramate twice daily. Typical total daily doses are usually between 200 milligrams (mg) to 400 mg for treatment of seizure disorders. For the treatment of bipolar disorders, dosages vary.

Beginning a course of treatment which includes topiramate requires a gradual dose-increasing regimen. The prescribing physician determines the proper beginning dosage and may raise a patient's daily dosage gradually over the course of several weeks. It may take several weeks to realize the full seizure-reducing benefits of topiramate.

A double dose of topiramate should not be taken to make up for a missed or forgotten dose. If a daily dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose is skipped. When discontinuing treatment with topiramate, physicians typically direct patients to gradually taper their daily dosages. Stopping the medicine suddenly may cause seizures to return or occur more frequently.

In the treatment of bipolar disorders, persons should not stop taking topiramate without consulting the prescribing physician. Stopping the medicine suddenly may cause seizures, or severely and suddenly alter a patient's mood.

Precautions

Topiramate is not habit-forming. A physician should be consulted before combining topiramate with certain non-prescription medications. Patients should avoid alcohol and CNS depressants (medicines that can make one drowsy or less alert, such as antihistimines, sleep medications, and some pain medications) while taking topiramate. Because topiramate may cause drowsiness, persons should not drive or operate heavy machinery until they know how they will react to the drug.

Persons taking topiramate, particularly those with predisposing factors, should maintain an adequate fluid intake in order to minimize the risk of kidney stone formation. Approximately 1.5% of people taking topiramate develop kidney stones.

Topiramate may not be suitable for persons with a history of liver or kidney disease, mental illness, high blood presure, angina (chest pain), irregular heartbeats, or other heart problems. Before beginning treatment with topiramate, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are pregnant or planning on becoming pregnant.

Topiramate may inhibit perspiration, causing body temperature to increase. Persons taking topiramate are at a greater risk for heat stroke, and should use caution during strenuous exercise, prolonged exposure during hot weather, and while using saunas or hot tubs.

Topiramate may cause birth defects. Use effective birth control while taking topiramate. Patients who become pregnant while taking topiramate should contact their physician immediately.

Side effects

Patients and their physicians should weigh the risks and benefits of topiramate before beginning treatment. Topiramate is usually well tolerated, but may cause a variety of usually mild side effects. Dizziness and drowsiness are the most frequently reported side effects of topiramate. Other possible side effects include:

• double vision
• tingling or prickly feeling of the extremeties
• language problems described as "trouble finding the right word"
• loss of appetite and nervousness (in children)

Many of these side effects disappear or occur less frequently during treatment as the body adjusts to the medication. However, if any symptoms persist or become too uncomfortable, the prescribing physician should be consulted.

Other, uncommon side effects of topiramate can lead to serious complications. A person taking topiramate who experiences any of the following symptoms should immediately contact their physician:

• blurred vision and eye pain
• extreme mood or mental changes
• shakiness or unsteady walking
• kidney stones
• difficulty breathing
• chest pain
• irregular heartbeat
• faintness or loss of consciousness

Interactions

Topiramate may have negative interactions with some antihistimines, antidepressants, antibiotics, and monoamine oxidase inhibitors (MAOIs). Other medications such as diazepam (Valium), phenobarbital (Luminal, Solfoton), nefazodone, metronidazole, acetazolamide (Diamox), lanoxin (Digoxin, Digitek), phenytoin (Dilantin), primidone, and propranolol (Inderal) may also need to be adjusted and closely monitored if taken with topiramate. Topiramate, like many other anticonvulsant medications, may decrease the effectiveness of oral contraceptives (birth control pills).

Resources

BOOKS

Devinsky, Orrin. Epilepsy: Patient and Family Guide, 2nd. ed. Philadelphia: F. A. Davis Co., 2001.

Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Toronto: Firefly Books, 2001.

OTHER

Ortho-McNeil Pharmaceuticals. "Information for People Taking TOPAMAX®." Topamax. (April 4, 2004). http://www.topamax.com/patients/index.htm.

"Topiramate." Medline Plus. National Library of Medicine. (April 4, 2004). http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a697012.html.

ORGANIZATIONS

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. http://www.aesnet.org.

Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. http://www.epilepsyfoundation.org.

Adrienne Wilmoth Lerner

Brand names: Topamax®

Chemical formula:

Drug Forms:
• Topiramate tablets or sprinkle capsules (below)
• Topiramate Oral capsule, sprinkles
• Topiramate Oral tablet

Español:
• Tabletas o cápsulas para espolvorear de topiramato
• Topiramato, Cápsula oral para espolvorear
• Topiramato, Tableta oral

Topiramate tablets or sprinkle capsules

What are topiramate tablets or sprinkle capsules?

TOPIRAMATE (Topamax®) is effective in helping to control seizures (convulsions) in adults or children with various forms of epilepsy. Topiramate may also be prescribed for other conditions, such as prevention of migraine headaches. Generic topiramate tablets or sprinkle-capsules are not yet available.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• cirrhosis of the liver or other liver disease
• depression
• diarrhea
• glaucoma
• kidney stones
• kidney disease
• lung disease
• metabolic acidosis
• on a ketogenic diet
• suicidal thoughts, plans, or attempt; a previous suicide attempt by you or a family member
• an unusual or allergic reaction to topiramate, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Take topiramate tablets and capsules by mouth. Swallow the tablets whole with a drink of water; do not crush or chew. The capsules can be swallowed whole or opened carefully and the contents sprinkled on about on a small amount of soft food, such as applesauce, pudding, ice cream, oatmeal, or yogurt. This mixture must be swallowed immediately; do not chew or store the sprinkles on the food for later use. Be sure to take the entire dose. You may take topiramate with meals. Take your doses at regular intervals. Do not take your medicine more often than directed.

Topiramate should be taken on a daily basis as prescribed by your health care professional for the prevention of migraine headaches. Topiramate should not be used to 'abort' or stop a migraine once it has started.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed. Topiramate has been used in children for the treatment of various seizure disorders.

What drug(s) may interact with topiramate?

• acetazolamide
• birth control pills or other hormones for birth control, including implants or injections
• bosentan
• carbamazepine
• dichlorphenamide
• digoxin
• ethanol
• hydrochlorothiazide
• medications for pain, sleep, or muscle relaxation
• methazolamide
• phenobarbital or primidone
• phenytoin
• pioglitazone
• probenecid
• sevelamer
• valproic acid

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking topiramate?

Visit your prescriber or health care professional for a regular check on your progress. Do not stop taking this medicine suddenly. This increases the risk of seizures if you are using this medicine to control epilepsy. Wear a Medic Alert bracelet or necklace. Carry an identification card with information about your condition, medications, and prescriber or health care professional.

You should drink plenty of fluids while taking this medicine. If you have had kidney stones in the past, this will help to reduce your chances of forming kidney stones.

If you have stomach pain, with nausea or vomiting and yellowing of your eyes or skin, call your health care provider immediately.

You may get drowsy, dizzy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. To reduce dizziness, do not sit or stand up quickly, especially if you are an older patient. Alcohol can increase drowsiness and dizziness. Avoid alcoholic drinks.

If you take birth control pills, this medicine may reduce their effectiveness at preventing pregnancy. Notify your prescriber or health care professional if you notice changes in your monthly cycles or bleeding patterns. You may want to discuss birth control options with your health care provider.

The use of this medicine may increase the chance of suicidal thoughts or actions. Pay special attention to how you are responding while on this medicine. Any worsening of mood, or thoughts of suicide or dying should be reported to your health care professional right away.

If you notice blurred vision, eye pain, or other eye problems, seek medical attention at once for an eye exam.

If you are going to have surgery, tell your prescriber or health care professional that you are taking this medicine.

What side effects may I notice from taking topiramate?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• agitation, restlessness, irritability, or other changes in mood
• decreased sweating and/or rise in body temperature
• difficulty breathing
• difficulty speaking
• difficulty walking or controlling muscle movements
• eye pain, redness or swelling
• hearing impairment
• kidney stones (severe pain in the side or back, or on urination)
• nose bleeds
• redness, blistering, peeling or loosening of the skin, including inside the mouth
• skin rash, itching
• stomach pain with nausea or vomiting
• swelling of the face, lips or tongue
• tingling, pain or numbness in the hands or feet
• unusual weakness or tiredness
• vision problems, like blurred vision
• vomiting
• worsening of mood, thoughts or actions of suicide or dying
• yellowing of the skin or eyes

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• back pain, joint aches and pains
• breast pain
• diarrhea, or constipation
• difficulty sleeping
• dizziness, drowsiness
• dry mouth
• headache
• heartburn or stomach acid reflux
• hot flashes
• loss of appetite
• menstrual disorder
• muscle aches or pains
• nausea
• swelling of the gums
• stomach upset, indigestion
• stuffy, runny nose
• sweating
• tiredness or weakness
• taste altered
• tremor

Where can I keep my medicine?

Keep out of reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F) in a tightly closed container. Protect from moisture. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Topiramate
Systematic (IUPAC) name
2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
Identifiers
CAS number	97240-79-4
ATC code	N03AX11
PubChem	5284627
DrugBank	APRD00237
ChemSpider	4447672
Chemical data
Formula	C12H21NO8S
Mol. mass	339.363 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	80%
Metabolism	30% hepatic, 70% is excreted unchanged
Half life	19 to 23 hours
Excretion	70% renal (in urine) in unchanged form
Therapeutic considerations
Pregnancy cat.	B3(AU) C(US)
Legal status	POM(UK) ℞-only(US)
Routes	Oral
Y(what is this?)  (verify)

Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics and Noramco, Inc., both being divisions of Johnson & Johnson. It was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceutical.^[1][2][3] 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.^[4] The last patent for topiramate in the U.S. was for pediatric use; this patent expired on February 28, 2009.^[5]

Contents 1 Uses 2 Pharmacology 3 Side effects 4 Interactions 5 Dosage 6 Overdose 7 References 8 External links

Uses

Topiramate treats epilepsy in children and adults. It is sometimes used as an antidepressant. In children it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is also Food and Drug Administration (FDA) approved for, and most frequently prescribed for, the prevention of migraines. Psychiatrists have used topiramate to treat bipolar disorder,^[6] but it is not FDA approved for this purpose. This drug has been investigated for use in treating alcoholism^[7][8] and obesity,^[9][10] especially to reduce binge eating.^[11][12]

The drug is also used in clinical trials to treat Post Traumatic Stress Disorder.^[13] A pilot study suggested that topiramate is effective against infantile spasms.^[14] Another study recommends topiramate as an effective treatment in the prevention of periventricular leukomalacia in preterm infants after an hypoxic-ischemic injury.^[15] Other off-label and investigational uses of topiramate include the treatment of bulimia nervosa,^[16] obsessive-compulsive disorder, alcoholism,^[8] smoking cessation,^[17] idiopathic intracranial hypertension, neuropathic pain,^[18] cluster headache,^[19] and cocaine dependence.^[20]

Pharmacology

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 has a complex mechanism of action ^[21] The drug enhances GABA-activated chloride channels. In addition, it inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors (but not NMDA receptors). There is evidence that topiramate has a specific effect on GluK1 (GluR5) kainate receptors ^[22]. 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.^[23]

Side effects

A GlaxoSmithKline-sponsored Phase IV study suggested that cognitive side effects may be more common with topiramate than with lamotrigine.^[24] In studies of healthy volunteers, 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.^{[citation needed]}

The side-effects reported by > 10% of subjects in at least 1 clinical study^[25] 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 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%)

Blood clots have occurred in people given topamax, but it has not been proved that these were caused by the drug. Drug withdrawal convulsions (fits) have been reported very rarely. Psychosis (often with paranoid delusions and prominent visual hallucinations) has also been reported.

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

The Food and Drug Administration (FDA) has notified prescribes that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly. 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. 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.

In other postmarketing research, a risk of decreased sweating and hyperthermia was discovered. Pediatric patients (children) are especially prone to this side-effect.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.^[26] This might be particularly important for women who take topiramate to prevent migraine attacks.

Most antiepileptic drugs have been associated with a statistically significant increase in suicidality, including Topamax.^[27]

Interactions

• As topiramate inhibits carbonic anhydrase, use with other inhibitors of carbonic anhydrase (e.g. acetazolamide) increases the risk of kidney stones.
• Enzyme inductors (e.g. carbamazepine) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.
• 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'.^[28]
• Oligohydrosis and hyperthermia were reported in post-marketing reports about topiramate; antimuscarinic drugs (like trospium) can aggravate these disorders.

Dosage

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. Common dosages for maintenance treatment are 100 to 200 mg daily. The highest dosage possible is 400 mg daily in divided doses.

Overdose

Symptoms of overdose may include but are not limited to:

• 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^{[citation needed]}
• 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.

References

1. ^ Maryanoff, Be; Nortey, So; Gardocki, Jf; Shank, Rp; Dodgson, Sp (May 1987). "Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds". Journal of medicinal chemistry 30 (5): 880–7. doi:10.1021/jm00388a023. ISSN 0022-2623. PMID 3572976.  edit
2. ^ Maryanoff, E.; Costanzo, J.; Nortey, O.; Greco, N.; Shank, P.; Schupsky, J.; Ortegon, P.; Vaught, L. (Apr 1998). "Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives". Journal of medicinal chemistry 41 (8): 1315–1343. doi:10.1021/jm970790w. ISSN 0022-2623. PMID 9548821.  edit
3. ^ B. E. Maryanoff and J. F. Gardocki, "Anticonvulsant sulfamate derivatives", U.S. Patent 4,513,006 (1985)
4. ^ http://www.medscape.com/viewarticle/544994
5. ^ http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020844&Product_No=002&table1=OB_Rx
6. ^ Arnone, D (Feb 2005). "Review of the use of Topiramate for treatment of psychiatric disorders". Annals of general psychiatry 4 (1): 5. doi:10.1186/1744-859X-4-5. PMID 15845141.  edit
7. ^ Johnson, B. (2003). "Oral topiramate for treatment of alcohol dependence: a randomised controlled trial". The Lancet 361: 1677–1685. doi:10.1016/S0140-6736(03)13370-3.  edit
8. ^ ^{a b} Johnson, B. A.; Rosenthal, N.; Capece, J. A.; Wiegand, F.; Mao, L.; Beyers, K.; McKay, A.; Ait-daoud, N. et al. (Oct 2007). "Topiramate for treating alcohol dependence: a randomized controlled trial" (Free full text). JAMA : the journal of the American Medical Association 298 (14): 1641–1651. doi:10.1001/jama.298.14.1641. ISSN 0098-7484. PMID 17925516. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=17925516.  edit
9. ^ Van, Ameringen; Mancini, C; Pipe, B; Campbell, M; Oakman, J (Nov 2002). "Topiramate treatment for SSRI-induced weight gain in anxiety disorders". The Journal of clinical psychiatry 63 (11): 981–4. ISSN 0160-6689. PMID 12444810.  edit
10. ^ Wilding, J.; Van Gaal, L.; Rissanen, A.; Vercruysse, F.; Fitchet, M.; Obes-002 Study, P. (Nov 2004). "A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects". International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 28 (11): 1399–1410. doi:10.1038/sj.ijo.0802783. ISSN 0307-0565. PMID 15486569.  edit
11. ^ Shapira NA, Goldsmith TD, McElroy SL (May 2000). "Treatment of binge-eating disorder with topiramate: a clinical case series". The Journal of Clinical Psychiatry 61 (5): 368–72. PMID 10847312.  edit
12. ^ McElroy, Sl; Arnold, Lm; Shapira, Na; Keck, Pe; Rosenthal, Nr; Karim, Mr; Kamin, M; Hudson, Ji (Feb 2003). "Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial" (Free full text). The American journal of psychiatry 160 (2): 255–61. doi:10.1176/appi.ajp.160.2.255. ISSN 0002-953X. PMID 12562571. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=.  edit
13. ^ Berlant, J; Van, Kammen (Jan 2002). "Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report" (Free full text). The Journal of clinical psychiatry 63 (1): 15–20. ISSN 0160-6689. PMID 11838620. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+7660-25-5.  edit
14. ^ Glauser, Ta; Clark, Po; Strawsburg, R (Dec 1998). "A pilot study of topiramate in the treatment of infantile spasms". Epilepsia 39 (12): 1324–8. doi:10.1111/j.1528-1157.1998.tb01331.x. ISSN 0013-9580. PMID 9860068.  edit
15. ^ Follett, L.; Deng, W.; Dai, W.; Talos, M.; Massillon, J.; Rosenberg, A.; Volpe, J.; Jensen, E. (May 2004). "Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate" (Free full text). The Journal of neuroscience : the official journal of the Society for Neuroscience 24 (18): 4412–4420. doi:10.1523/JNEUROSCI.0477-04.2004. ISSN 0270-6474. PMID 15128855. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=15128855.  edit
16. ^ Hoopes, Sp; Reimherr, Fw; Hedges, Dw; Rosenthal, Nr; Kamin, M; Karim, R; Capece, Ja; Karvois, D (Nov 2003). "Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures". The Journal of clinical psychiatry 64 (11): 1335–41. ISSN 0160-6689. PMID 14658948.  edit
17. ^ Khazaal, Y.; Cornuz, J.; Bilancioni, R.; Zullino, F. (Jun 2006). "Topiramate for smoking cessation". Psychiatry and clinical neurosciences 60 (3): 384–388. doi:10.1111/j.1440-1819.2006.01518.x. ISSN 1323-1316. PMID 16732758.  edit
18. ^ Chong, Ms; Libretto, Se (Jan 2003). "The rationale and use of topiramate for treating neuropathic pain". The Clinical journal of pain 19 (1): 59–68. doi:10.1097/00002508-200301000-00008. ISSN 0749-8047. PMID 12514458.  edit
19. ^ Láinez, Mj; Pascual, J; Pascual, Am; Santonja, Jm; Ponz, A; Salvador, A (Jul 2003). "Topiramate in the prophylactic treatment of cluster headache". Headache 43 (7): 784–9. doi:10.1046/j.1526-4610.2003.03137.x. ISSN 0017-8748. PMID 12890134.  edit
20. ^ http://clinicaltrials.gov/ct2/show/NCT00685178?recr=Open&intr=%22Cocaine%22&rank=20
21. ^ Rogawski, A.; Löscher, W. (Jul 2004). "The neurobiology of antiepileptic drugs". Nature reviews. Neuroscience 5 (7): 553–564. doi:10.1038/nrn1430. ISSN 1471-003X. PMID 15208697.  edit
22. ^ Braga, F.; Aroniadou-Anderjaska, V.; Li, H.; Rogawski, A. (Aug 2009). "Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons". The Journal of pharmacology and experimental therapeutics 330 (2): 558–566. doi:10.1124/jpet.109.153908. ISSN 0022-3565. PMID 19417176.  edit
23. ^ Kudin, P.; Debska-Vielhaber, G.; Vielhaber, S.; Elger, E.; Kunz, S. (Dec 2004). "The mechanism of neuroprotection by topiramate in an animal model of epilepsy". Epilepsia 45 (12): 1478–1487. doi:10.1111/j.0013-9580.2004.13504.x. ISSN 0013-9580. PMID 15571505.  edit
24. ^ Blum, D.; Meador, K.; Biton, V.; Fakhoury, T.; Shneker, B.; Chung, S.; Mills, K.; Hammer, A. et al. (Aug 2006). "Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy". Neurology 67 (3): 400–406. doi:10.1212/01.wnl.0000232737.72555.06. ISSN 0028-3878. PMID 16894098.  edit
25. ^ Roy, Chengappa; Schwarzman, Lk; Hulihan, Jf; Xiang, J; Rosenthal, Nr; Clinical, Affairs (Nov 2006). "Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial". The Journal of clinical psychiatry 67 (11): 1698–706. ISSN 0160-6689. PMID 17196048.  edit
26. ^ Hunt, S.; Russell, A.; Smithson, H.; Parsons, L.; Robertson, I.; Waddell, R.; Irwin, B.; Morrison, J. et al. (Jul 2008). "Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register". Neurology 71 (4): 272–276. doi:10.1212/01.wnl.0000318293.28278.33. ISSN 0028-3878. PMID 18645165.  edit
27. ^ http://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4344s1_09_01_Trileptal%20slides.pdf
28. ^ FDA.gov

External links

Wikimedia Commons has media related to: Topiramate

• Topamax (topiramate): Treatment for Migraine Prevention
• 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
• RxList.com: Topiramate
• Focus on Topiramate - a new anti-epileptic, Ben Green, Priory Lodge Education Ltd., 1997-99. Version 1.1

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