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Topiramate
Indications
Topiramate is an antiepileptic drug (AED), a group of medications primarily indicated for treating seizure disorders, reflecting their designation as "antiepileptic." These drugs are also traditionally used as mood stabilizers in psychiatry, with expanding applications over time.[1] Topiramate, specifically, is an anticonvulsant that received FDA approval in 1996 for use as monotherapy and adjunctive therapy in epilepsy, as well as for treating migraine disorders.[2]
FDA-Approved Indications
Topiramate is approved as monotherapy for epilepsy for individuals aged 2 years and older with primary generalized onset tonic-clonic or partial-onset seizures.[3] Additionally, it is sanctioned for adjunctive therapy in adults and pediatric populations from ages 2 to 16 years with primary generalized onset tonic-clonic seizures, partial-onset seizures, and for those aged 2 years or older with seizures associated with Lennox-Gastaut syndrome.[4][5] Topiramate is approved for migraine prevention in adults. Furthermore, it is approved for chronic weight management in individuals with a body mass index over 30 kg/m2 and as part of a fixed-dose combination with phentermine for obesity management.[6][7][8]
Off-Label Uses
Topiramate has numerous off-label applications, including the treatment of neuropathic pain, psychotropic drug-induced weight gain, alcohol and tobacco dependence, prevention of cluster headaches, binge eating disorder, bulimia nervosa, and obesity with hypertension. Topiramate is also used in preventing neuralgiform attacks, adjunctive therapy in bipolar disorder, and managing unipolar depression, borderline personality disorder, obsessive-compulsive disorder, posttraumatic stress disorder, Tourette syndrome, Prader-Willi syndrome, and essential tremor.[9][10] Topiramate has shown efficacy in treating alcohol use disorder in individuals unresponsive to naltrexone/acamprosate and is considered as effective and safe as naltrexone for reducing heavy alcohol consumption, irrespective of genetic polymorphisms.[11] Additionally, topiramate is utilized for binge eating disorders.[12][13] An emerging drug-device combination using the SipNose intranasal delivery platform, which facilitates direct nose-to-brain transport, is being developed for binge eating disorder treatment. However, it has not yet received FDA approval.[14]
Mechanism of Action
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Mechanism of Action
Although topiramate's precise mechanism of action remains unclear, sufficient evidence explains its anticonvulsant activity.[15][16] Topiramate blocks voltage-gated sodium channels, likely leading to sustained depolarization control during seizures.[17] Topiramate reduces membrane depolarization via AMPA/Kainate receptors and enhances GABA-A receptor activity, strengthening inhibitory effects.[6] Additionally, topiramate acts as a weak carbonic anhydrase inhibitor; acidosis in the brain partially protects against seizures by downregulating NMDA receptor activity. Overall, the influence of topiramate on these channels is the primary explanation for its antiepileptic effects.[18][19] The efficacy of topiramate in migraine is likely due to inhibitory effects on AMPA and kainate subtypes of glutamate receptors and, to a lesser extent, voltage-gated calcium channels. Calcitonin gene-related peptide (CGRP) has emerged as a therapeutic target for migraine. Topiramate inhibits the release of CGRP and glutamate from trigeminal neurovascular nerve endings, effectively disrupting cortical spreading depression and demonstrating efficacy in managing both epilepsy and migraine.[20] In individuals with frequent episodic migraines, topiramate may prevent the transition to chronic migraine.[21]
Pharmacokinetics
Absorption: Topiramate is well absorbed from the gastrointestinal tract, with peak plasma levels typically achieved in 2 to 3 hours. The bioavailability exceeds 80%. Concomitant ingestion of food delays the time to reach peak plasma concentration but does not significantly alter the extent of absorption. Thus, topiramate can be administered without regard to meals. Topiramate follows linear and predictable pharmacokinetics over the recommended dose range (15 to 400 mg/d).
Distribution: Topiramate displays plasma protein binding ranging from 15% to 41%. The fraction of bound topiramate decreases as blood concentration increases.
Metabolism: Topiramate undergoes metabolism through hydroxylation, hydrolysis, and glucuronidation.
Excretion: Topiramate is eliminated primarily through renal excretion, both unchanged and as metabolites. Clearance in adults is 20 to 30 mL/min. The mean plasma elimination half-life is approximately 21 hours, varying with age and the concomitant use of enzyme-inducing or inhibiting drugs. Clearance increases in patients taking concomitant enzyme-inducing drugs such as phenytoin, barbiturates, and carbamazepine.[22]
Administration
Available Dosage Forms and Strengths
Topiramate is available for both adult and pediatric populations in 2 oral preparations: immediate-release (taken twice daily) and extended-release (taken once daily). Patients should not crush the tablets due to their bitter taste. There is also a sprinkle capsule formulation that may be added to a small amount of soft food; administration of topiramate may occur without regard to meals. The oral solution is available at a concentration of 25 mg/mL. Alcohol should be avoided for 6 hours before and after administering topiramate.[22] Importantly, some extended-release formulations of topiramate are not bioequivalent.
Adult Dosage
Monotherapy for partial-onset seizures and primary generalized tonic-clonic seizures: The suggested dose for topiramate in adults and pediatric patients 10 years and older is 400 mg/d in 2 divided doses. A slow titration schedule of 25 to 50 mg/d in weekly increments is preferred to decrease the frequency of adverse effects.[23]
Adjunctive therapy for primary generalized tonic-clonic seizures, partial-onset seizures, or Lennox-Gastaut Syndrome: The suggested total daily dose of topiramate as an adjunctive treatment in adults with partial onset seizures is 200 to 400 mg/d in 2 divided doses for primary generalized tonic-clonic seizures. Treatment should be initiated at a lower dose (25 to 50 mg/d) followed by an up-titration of 25 to 50 mg/d weekly.[24][25]
Migraine prevention: According to guidelines from the American Academy of Neurology, topiramate is an effective therapy for migraine prevention (level A), significantly decreasing the frequency and severity of migraine attacks. The recommended dose range is 25 to 50 mg. Patients with a favorable response to topiramate pharmacotherapy within 4 to 8 weeks should continue treatment for at least 6 months to achieve maximum benefit. Dose escalation up to 200 mg may be required in selected patients.[26] According to consensus from the American Academy of Neurology and American Headache Society, children and adolescents receiving topiramate experience a decrease in headache days and migraine attacks.[27]
Specific Patient Populations
Hepatic impairment: Topiramate plasma concentrations may be increased in patients with hepatic impairment. However, the increase is not significant, and no dose adjustment is generally suggested.
Renal impairment: Half the standard dose is recommended for moderate to severe renal impairment and ESRD. As topiramate is removed by dialysis, a supplemental dose may be required during hemodialysis.[28]
Pregnancy considerations: A topiramate dose of less than 200 mg daily does not affect the pharmacokinetic levels of oral contraceptive pills containing 35 μg of ethinyl estradiol. The dose of topiramate used for migraine prevention (25 to 50 mg) is not supposed to reduce contraceptive efficacy.[29] According to clinical data from the NAAED pregnancy registry, there may be an increased risk of oral cleft (1.4%) when infants are exposed to topiramate. First-trimester exposure to topiramate monotherapy is associated with an increased frequency of cleft lip with or without cleft palate and small for gestational age. A study indicates an increased risk of autism spectrum disorders and intellectual disability due to prenatal exposure to topiramate.[30] Topiramate should be considered in pregnancy only after a comprehensive risk-benefit evaluation.[26]
Breastfeeding considerations: Maternal doses of topiramate up to 200 mg daily produce a low concentration in infant serum. Sedation and diarrhea have been reported in breastfed infants, but most infants tolerate the drug in milk well. The infant should be monitored for diarrhea, drowsiness, irritability, weight gain, and developmental milestones. Caution is required in exclusively breastfed infants and simultaneous use of antiepileptics or psychotropic drugs.[31]
Pediatric patients: The meta-analysis aimed to evaluate the efficacy and safety of topiramate in pediatric migraine. Topiramate was associated with higher rates of adverse drug reactions such as weight loss and paresthesia. Topiramate is effective in reducing the number of monthly headache days in patients under the age of 18 who experience migraines, thus alleviating the burden of migraine-related symptoms.[32] Oligohidrosis, hyperthermia, and reduction in bone mineral density have been reported in pediatric patients.
Older patients: Dosage adjustment of topiramate may be required for patients with creatinine clearance <70 mL/min/1.73 m2.
Adverse Effects
Adverse effects are dose-dependent and vary between patients with epilepsy and migraine, as the trials use different doses based on the condition.[22]
The most common adverse effects in epilepsy trials included central nervous system involvement (paresthesia, fatigue, cognitive problems, dizziness, somnolence, psychomotor slowing, memory/concentration difficulties, nervousness, confusion), endocrine/metabolism issues (weight loss, anorexia), respiratory problems (infection), and miscellaneous effects (fever, flushing).[33][34] In trials involving patients with migraine, the most common adverse effects are paresthesia and dysgeusia.[35]
Severe adverse drug reactions include:
- Acute myopia and secondary angle-closure glaucoma [36]
- Oligohidrosis and hyperthermia (uncommon, reversible with cessation of the drug) [37]
- Metabolic acidosis: Due to inhibition of carbonic anhydrase isoenzymes, topiramate can lead to metabolic acidosis secondary to type II renal tubular acidosis, elevated urine pH, reduced urine citrate, hypercalciuria, calcium phosphate stone formation, bone mineralization defects.[38]
- Suicidal behavior and ideation [39]
- Cognitive/neuropsychiatric adverse reactions: The influence of topiramate on the hippocampus-related memory processes influences spatial memory but does not significantly affect the learning process.[40]
- Fetal toxicity: Exposure during pregnancy is associated with congenital malformations and developmental delay. Increased risk of recurrent malformations in future pregnancies.[41]
- Hyperammonemia and encephalopathy: One case report describes a young patient developing metabolic encephalopathy with hypoxic respiratory failure, most likely due to concurrent use of valproic acid and topiramate. Clinicians should be cautious of possible hyperammonemia encephalopathy in patients taking these medications presenting with impaired consciousness and cognitive decline.[4]
- Kidney stones: Long-term topiramate administration could induce urolithiasis; therefore, blood testing for acid-base balance, urinary pH, and citrate is recommended in patients with kidney stones.[42]
- Paresthesia is the most common cause of discontinuation.[43]
- Adjustment of dose in renal failure: Dose adjustment is necessary for patients with moderate-to-severe renal impairment.[44]
- Hepatotoxicity: A literature review indicates that <1% of subjects have increased serum aminotransferase levels during long-term topiramate therapy. The hepatotoxicity is believed to be due to a toxic intermediate formation. Cases with lactic acidosis and hyperammonemia may be caused by mitochondrial dysfunction.[45]
Drug-Drug Interactions
- Concurrent use of topiramate and metformin increases the risk of metabolic acidosis. Simultaneous use is contraindicated.[46]
- Topiramate increases the oral clearance of high-dose estrogen contraceptives and can lead to contraception failure (>200 mg/d).[47]
- Clearance of topiramate may be reduced when used with amitriptyline. Use with caution.[47]
- Concurrent administration of topiramate with carbamazepine requires dose adjustments due to reduced topiramate concentrations.[48]
- Concurrent use of carbonic anhydrase inhibitors like acetazolamide, dorzolamide, and brinzolamide with topiramate may increase the risk of metabolic acidosis and nephrolithiasis. Avoid co-administration.[16]
- Concurrent use of topiramate with benzodiazepines, alcohol, thalidomide, and bromperidol can cause sedation and excessive CNS depression.
- An increase in systemic exposure to lithium may occur with high doses of topiramate (600 mg/d). Therefore, it is advisable to monitor lithium levels when co-administering high-dose topiramate.
Contraindications
Topiramate is a relatively safe drug, and the list of absolute contraindications is minimal. As a carbonic anhydrase inhibitor, topiramate can precipitate the development of metabolic acidosis and is, therefore, contraindicated in individuals currently with (or prone to) metabolic acidosis. Other contraindications include those with a history of a proven allergy to topiramate or individuals who have consumed (or will consume) alcohol within 6 hours.[26]
Warnings and Precautions
Acute myopia and secondary angle-closure glaucoma: Ophthalmologic findings associated with topiramate may include myopia, increased intraocular pressure, ocular hyperemia, macular striae, choroidal detachment, anterior chamber shallowing, mydriasis, and retinal pigment epithelial detachment. Supraciliary effusion can precipitate anterior displacement of the lens and iris, leading to secondary angle-closure glaucoma. Symptoms typically emerge within one month of initiating topiramate. Unlike primary narrow-angle glaucoma, secondary-angle closure glaucoma induced by topiramate can occur in pediatric and adult populations. Discontinuation of topiramate may be required.[36] Drug-induced choroidal effusion syndrome should be considered as a possible cause of bilateral acute angle-closure glaucoma in patients with myopia and a shallow anterior chamber.[49]
Negative effects on growth: According to product labeling, topiramate can reduce body weight in pediatric populations. Additionally, a reduction in height velocity and height change has been noted with topiramate use. Adverse effects on weight and height are evident across all age subgroups of topiramate users. Therefore, careful growth monitoring is essential in children receiving prolonged topiramate treatment.
Other warnings related to topiramate use are covered in adverse drug reactions.
Monitoring
Baseline and periodic serum bicarbonate levels are required for individuals on topiramate due to concerns about metabolic acidosis. Healthcare professionals should also monitor renal function tests. The American Epilepsy Society states that antiepileptic drug-level testing, including for topiramate, is not routinely necessary when seizures are controlled without adverse effects. However, monitoring topiramate levels is advisable in special cases, such as weight-based dose adjustments for young children, assessing patient adherence, managing polypharmacy, and detecting suspected toxicity. Due to variability in topiramate plasma concentration with concomitant antiepileptic drug use, monitoring plasma concentration may be beneficial for optimizing drug dosage.[19][50] Healthcare professionals should also obtain serum prolactin levels to differentiate between psychogenic nonepileptic seizures (PNES) and generalized tonic-clonic or complex partial seizures.[51]
Healthcare professionals should monitor for a reduction in the frequency of the most debilitating seizures, such as drop attacks and tonic-clonic seizures when using topiramate for Lennox-Gastaut syndrome (LGS).[25]
They should also monitor for a reduction in the frequency and severity of headaches. A decrease in the frequency of migraine days is a key measure of the efficacy of migraine prevention.[52] A network meta-analysis reported that topiramate increases the proportion of patients achieving a reduction of 50% or more in monthly migraine days compared to those receiving a placebo.[53]
Toxicity
Signs and Symptoms of Overdose
Symptoms of toxicity include sedation, speech disturbances, blurred vision, agitation, ataxia, convulsions, and abdominal pain. Arterial blood gas analysis in a topiramate overdose usually shows hyperchloremic normal anion gap metabolic acidosis.[54]
In 7 cases of topiramate toxicity observed by Poison Control Centers in Poland, somnolence was the most common symptom (66.7%), along with agitation, mydriasis, and vertigo (33.4%). One individual experienced 3 tonic-clonic seizures. There were no fatalities or long-term consequences.[55]
Management of Overdose
Currently, no specific antidote is available. If symptoms are refractory to ongoing treatment, hemodialysis can reduce topiramate concentrations.[28] A recent case report involved a 32-year-old woman who presented following the intentional ingestion of 36 g of topiramate. Following hemodialysis, significant neurological improvement occurred, including the resolution of encephalopathic features and cessation of myoclonic jerking. Gas chromatography/mass spectrometry showed a marked reduction in topiramate levels, underscoring the effectiveness of hemodialysis in managing severe topiramate toxicity by facilitating rapid clearance of the drug.[56]
Enhancing Healthcare Team Outcomes
Topiramate is FDA-approved for various types of epilepsy, migraine, and Lennox-Gastaut syndrome; however, it has numerous off-label uses and a significant adverse drug reaction profile. Therefore, healthcare professionals must continually educate themselves on the most up-to-date information regarding new medical information. Clinicians prescribe topiramate for specific indications. Neurologist and epileptologist consultations are required for refractory seizures and seizures associated with Lennox-Gastaut syndrome. For various off-label uses, consultation with other specialties may be essential. Nurses monitor for any adverse events and patient compliance. Pharmacists are crucial in verifying medication reconciliation and reporting significant interactions to the prescriber.
The brand name of topiramate may be confused with the brand name of a commonly used extended-release β-blocker. Consequently, pharmacists must be careful while dispensing the drug.[57] Emergency medicine physicians and nurses rapidly stabilize the patient in an overdose. Critical care physicians and medical toxicologists are crucial in managing patients with massive overdoses. Once the patient is stable, a psychiatric evaluation and support are necessary. Interprofessional coordination between clinicians (MDs, DOs, NPs, PAs), nurses, pharmacists, specialists, and other healthcare workers is essential to decrease adverse events and improve patient outcomes related to topiramate therapy.
References
Lieb K, Völlm B, Rücker G, Timmer A, Stoffers JM. Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials. The British journal of psychiatry : the journal of mental science. 2010 Jan:196(1):4-12. doi: 10.1192/bjp.bp.108.062984. Epub [PubMed PMID: 20044651]
Level 1 (high-level) evidenceCohen JB, Gadde KM. Weight Loss Medications in the Treatment of Obesity and Hypertension. Current hypertension reports. 2019 Feb 12:21(2):16. doi: 10.1007/s11906-019-0915-1. Epub 2019 Feb 12 [PubMed PMID: 30747357]
Kazerooni R, Lim J. Topiramate-Associated Weight Loss in a Veteran Population. Military medicine. 2016 Mar:181(3):283-6. doi: 10.7205/MILMED-D-14-00636. Epub [PubMed PMID: 26926755]
Raru Y, Zeid F. Hypoxic respiratory failure due to hyperammonemic encephalopathy induced by concurrent use of valproic acid and topiramate, a case report and review of the literature. Respiratory medicine case reports. 2018:25():1-3. doi: 10.1016/j.rmcr.2018.05.026. Epub 2018 May 30 [PubMed PMID: 29872630]
Level 3 (low-level) evidenceCastle D, Bosanac P, Rossell S. Treating OCD: what to do when first-line therapies fail. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists. 2015 Aug:23(4):350-3. doi: 10.1177/1039856215590027. Epub 2015 Jun 23 [PubMed PMID: 26104775]
Minton GC, Miller AD, Bookstaver PB, Love BL. Topiramate: safety and efficacy of its use in the prevention and treatment of migraine. Journal of central nervous system disease. 2011:3():155-68. doi: 10.4137/JCNSD.S4365. Epub 2011 Jun 23 [PubMed PMID: 23861645]
Kim A, Nguyen J, Babaei M, Kim A, Geller DH, Vidmar AP. A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity. Adolescent health, medicine and therapeutics. 2023:14():125-140. doi: 10.2147/AHMT.S383454. Epub 2023 Aug 23 [PubMed PMID: 37641650]
Level 3 (low-level) evidenceSmith SM, Meyer M, Trinkley KE. Phentermine/topiramate for the treatment of obesity. The Annals of pharmacotherapy. 2013 Mar:47(3):340-9 [PubMed PMID: 23482732]
Arnone D. Review of the use of Topiramate for treatment of psychiatric disorders. Annals of general psychiatry. 2005 Feb 16:4(1):5 [PubMed PMID: 15845141]
Soyka M, Müller CA. Pharmacotherapy of alcoholism - an update on approved and off-label medications. Expert opinion on pharmacotherapy. 2017 Aug:18(12):1187-1199. doi: 10.1080/14656566.2017.1349098. Epub 2017 Jul 24 [PubMed PMID: 28658981]
Level 3 (low-level) evidenceMorley KC, Kranzler HR, Luquin N, Jamshidi N, Adams C, Montebello M, Tremonti C, Dali G, Logge W, Baillie A, Teesson M, Trent R, Haber PS. Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial. The American journal of psychiatry. 2024 May 1:181(5):403-411. doi: 10.1176/appi.ajp.20230666. Epub [PubMed PMID: 38706338]
Level 1 (high-level) evidenceMcElroy SL, Hudson JI, Capece JA, Beyers K, Fisher AC, Rosenthal NR, Topiramate Binge Eating Disorder Research Group. Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study. Biological psychiatry. 2007 May 1:61(9):1039-48 [PubMed PMID: 17258690]
Himmerich H, Lewis YD, Conti C, Mutwalli H, Karwautz A, Sjögren JM, Uribe Isaza MM, Tyszkiewicz-Nwafor M, Aigner M, McElroy SL, Treasure J, Kasper S, WFSBP Task Force on Eating Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2023 Apr 24:():1-64. doi: 10.1080/15622975.2023.2179663. Epub 2023 Apr 24 [PubMed PMID: 37350265]
Kobo-Greenhut A, Zohar-Beja A, Hadar L, Itzhaki L, Karasik A, Caraco Y, Frankenthal H, Shahaf D, Ekstein D, Shichor I, Gur E. SipNose-topiramate: a potential novel approach to binge eating management. Journal of eating disorders. 2023 Jun 26:11(1):102. doi: 10.1186/s40337-023-00825-9. Epub 2023 Jun 26 [PubMed PMID: 37365668]
Parikh SK, Silberstein SD. Current Status of Antiepileptic Drugs as Preventive Migraine Therapy. Current treatment options in neurology. 2019 Mar 18:21(4):16. doi: 10.1007/s11940-019-0558-1. Epub 2019 Mar 18 [PubMed PMID: 30880369]
Supuran CT. Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors. Expert opinion on drug metabolism & toxicology. 2016:12(4):423-31. doi: 10.1517/17425255.2016.1154534. Epub 2016 Mar 3 [PubMed PMID: 26878088]
Level 3 (low-level) evidenceLauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2011 Jan:31(1):17-35. doi: 10.1038/jcbfm.2010.191. Epub 2010 Nov 3 [PubMed PMID: 21045864]
Vega D, Maalouf NM, Sakhaee K. Increased propensity for calcium phosphate kidney stones with topiramate use. Expert opinion on drug safety. 2007 Sep:6(5):547-57 [PubMed PMID: 17877442]
Level 3 (low-level) evidenceContin M, Riva R, Albani F, Avoni P, Baruzzi A. Topiramate therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Therapeutic drug monitoring. 2002 Jun:24(3):332-7 [PubMed PMID: 12021622]
Level 1 (high-level) evidenceHu C, Zhang Y, Tan G. Advances in topiramate as prophylactic treatment for migraine. Brain and behavior. 2021 Oct:11(10):e2290. doi: 10.1002/brb3.2290. Epub 2021 Sep 2 [PubMed PMID: 34472696]
Level 3 (low-level) evidenceKowacs PA, Sampaio Rocha-Filho PA, Peres MFP, Edvinsson L. The history and rationale of the development of new drugs for migraine treatment. Arquivos de neuro-psiquiatria. 2023 Dec:81(12):1084-1097. doi: 10.1055/s-0043-1777723. Epub 2023 Dec 29 [PubMed PMID: 38157876]
Khalil NY, AlRabiah HK, Al Rashoud SS, Bari A, Wani TA. Topiramate: Comprehensive profile. Profiles of drug substances, excipients, and related methodology. 2019:44():333-378. doi: 10.1016/bs.podrm.2018.11.005. Epub 2019 Jan 14 [PubMed PMID: 31029222]
Alfaris N, Minnick AM, Hopkins CM, Berkowitz RI, Wadden TA. Combination phentermine and topiramate extended release in the management of obesity. Expert opinion on pharmacotherapy. 2015 Jun:16(8):1263-74. doi: 10.1517/14656566.2015.1041505. Epub [PubMed PMID: 25958964]
Level 3 (low-level) evidenceCoppola G, Caliendo G, Veggiotti P, Romeo A, Tortorella G, De Marco P, Pascotto A. Topiramate as add-on drug in children, adolescents and young adults with Lennox-Gastaut syndrome: an Italian multicentric study. Epilepsy research. 2002 Sep:51(1-2):147-53 [PubMed PMID: 12350390]
Level 1 (high-level) evidenceAsadi-Pooya AA. Lennox-Gastaut syndrome: a comprehensive review. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018 Mar:39(3):403-414. doi: 10.1007/s10072-017-3188-y. Epub 2017 Nov 9 [PubMed PMID: 29124439]
Silberstein SD. Topiramate in Migraine Prevention: A 2016 Perspective. Headache. 2017 Jan:57(1):165-178. doi: 10.1111/head.12997. Epub 2016 Nov 30 [PubMed PMID: 27902848]
Level 3 (low-level) evidenceOskoui M, Pringsheim T, Billinghurst L, Potrebic S, Gersz EM, Gloss D, Holler-Managan Y, Leininger E, Licking N, Mack K, Powers SW, Sowell M, Victorio MC, Yonker M, Zanitsch H, Hershey AD. Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2019 Sep 10:93(11):500-509. doi: 10.1212/WNL.0000000000008105. Epub 2019 Aug 14 [PubMed PMID: 31413170]
Level 1 (high-level) evidenceManitpisitkul P, Curtin CR, Shalayda K, Wang SS, Ford L, Heald DL. Pharmacokinetics of topiramate in patients with renal impairment, end-stage renal disease undergoing hemodialysis, or hepatic impairment. Epilepsy research. 2014 Jul:108(5):891-901. doi: 10.1016/j.eplepsyres.2014.03.011. Epub 2014 Mar 26 [PubMed PMID: 24725807]
. Gynecologic Management of Adolescents and Young Women With Seizure Disorders: ACOG Committee Opinion, Number 806. Obstetrics and gynecology. 2020 May:135(5):e213-e220. doi: 10.1097/AOG.0000000000003827. Epub [PubMed PMID: 32332416]
Level 3 (low-level) evidenceBjørk MH, Zoega H, Leinonen MK, Cohen JM, Dreier JW, Furu K, Gilhus NE, Gissler M, Hálfdánarson Ó, Igland J, Sun Y, Tomson T, Alvestad S, Christensen J. Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability. JAMA neurology. 2022 Jul 1:79(7):672-681. doi: 10.1001/jamaneurol.2022.1269. Epub [PubMed PMID: 35639399]
. Topiramate. Drugs and Lactation Database (LactMed®). 2006:(): [PubMed PMID: 30000318]
Wu X, Zhang Y, Lu M, Yu X, Ye X, Wang X, Shan P. The Efficacy and Safety of Topiramate in the Prevention of Pediatric Migraine: An Update Meta-Analysis. Frontiers in pediatrics. 2020:8():28. doi: 10.3389/fped.2020.00028. Epub 2020 Feb 27 [PubMed PMID: 32175291]
Level 1 (high-level) evidenceNovotny E, Renfroe B, Yardi N, Nordli D, Ness S, Wang S, Weber T, Kurland CL, Yuen E, Eerdekens M, Venkatraman L, Nye JS, Ford L. Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures. Neurology. 2010 Mar 2:74(9):714-20. doi: 10.1212/WNL.0b013e3181d1cd4c. Epub 2010 Jan 20 [PubMed PMID: 20089937]
Level 1 (high-level) evidenceKanner AM, Ashman E, Gloss D, Harden C, Bourgeois B, Bautista JF, Abou-Khalil B, Burakgazi-Dalkilic E, Llanas Park E, Stern J, Hirtz D, Nespeca M, Gidal B, Faught E, French J. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018 Jul 10:91(2):74-81. doi: 10.1212/WNL.0000000000005755. Epub 2018 Jun 13 [PubMed PMID: 29898971]
Level 1 (high-level) evidencePulman J, Jette N, Dykeman J, Hemming K, Hutton JL, Marson AG. Topiramate add-on for drug-resistant partial epilepsy. The Cochrane database of systematic reviews. 2014 Feb 25:(2):CD001417. doi: 10.1002/14651858.CD001417.pub3. Epub 2014 Feb 25 [PubMed PMID: 24570033]
Level 1 (high-level) evidenceSierra-Rodríguez MA, Rodríguez-Vicente L, Chavarri-García JJ, Del Río-Mayor JL. Acute narrow-angle glaucoma induced by topiramate with acute myopia and macular striae: A case report. Archivos de la Sociedad Espanola de Oftalmologia. 2019 Mar:94(3):130-133. doi: 10.1016/j.oftal.2018.11.005. Epub 2018 Dec 24 [PubMed PMID: 30591244]
Level 3 (low-level) evidenceKarachristianou S, Papamichalis E, Sarantopoulos A, Boura P, Georgiadis G. Hypohidrosis induced by topiramate in an adult patient. Epileptic disorders : international epilepsy journal with videotape. 2013 Jun:15(2):203-6. doi: 10.1684/epd.2013.0568. Epub [PubMed PMID: 23773932]
Level 3 (low-level) evidenceGupta S, Gao JJ, Emmett M, Fenves AZ. Topiramate and metabolic acidosis: an evolving story. Hospital practice (1995). 2017 Dec:45(5):192-195. doi: 10.1080/21548331.2017.1370969. Epub 2017 Sep 1 [PubMed PMID: 28828886]
Abraham G. Topiramate-induced suicidality. Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2003 Mar:48(2):127-8 [PubMed PMID: 12655915]
Level 3 (low-level) evidencePietrzak B, Konopka A, Wojcieszak J. Effect of topiramate on hippocampus-dependent spatial memory in rats. Pharmacological reports : PR. 2013:65(5):1152-62 [PubMed PMID: 24399711]
Level 3 (low-level) evidenceCampbell E, Devenney E, Morrow J, Russell A, Smithson WH, Parsons L, Robertson I, Irwin B, Morrison PJ, Hunt S, Craig J. Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero. Epilepsia. 2013 Jan:54(1):165-71. doi: 10.1111/epi.12001. Epub 2012 Nov 21 [PubMed PMID: 23167802]
Salek T, Andel I, Kurfurstova I. Topiramate induced metabolic acidosis and kidney stones - a case study. Biochemia medica. 2017 Jun 15:27(2):404-410. doi: 10.11613/BM.2017.042. Epub [PubMed PMID: 28694730]
Level 3 (low-level) evidenceGolpayegani M, Salari F, Gharagozli K. Newer Antiepileptic Drugs Discontinuation due to Adverse Effects: An Observational Study. Annals of Indian Academy of Neurology. 2019 Jan-Mar:22(1):27-30. doi: 10.4103/aian.AIAN_25_18. Epub [PubMed PMID: 30692756]
Level 2 (mid-level) evidenceYamamoto Y, Usui N, Nishida T, Mori M, Takahashi Y, Imai K, Kagawa Y, Inoue Y. Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment. Therapeutic drug monitoring. 2018 Feb:40(1):144-147. doi: 10.1097/FTD.0000000000000461. Epub [PubMed PMID: 29095797]
. Topiramate. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012:(): [PubMed PMID: 31643944]
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. The Cochrane database of systematic reviews. 2010 Apr 14:2010(4):CD002967. doi: 10.1002/14651858.CD002967.pub4. Epub 2010 Apr 14 [PubMed PMID: 20393934]
Level 2 (mid-level) evidenceBialer M, Doose DR, Murthy B, Curtin C, Wang SS, Twyman RE, Schwabe S. Pharmacokinetic interactions of topiramate. Clinical pharmacokinetics. 2004:43(12):763-80 [PubMed PMID: 15355124]
Mack CJ, Kuc S, Mulcrone SA, Pilley A, Grünewald RA. Interaction of topiramate with carbamazepine: two case reports and a review of clinical experience. Seizure. 2002 Oct:11(7):464-7 [PubMed PMID: 12237076]
Level 3 (low-level) evidenceLobo S, Lobo GJ. Topiramate-induced ocular complications: case series. Romanian journal of ophthalmology. 2024 Jan-Mar:68(1):72-74. doi: 10.22336/rjo.2024.14. Epub [PubMed PMID: 38617722]
Level 2 (mid-level) evidenceBourgeois BF. Pharmacokinetics and metabolism of topiramate. Drugs of today (Barcelona, Spain : 1998). 1999 Jan:35(1):43-8 [PubMed PMID: 12973408]
Chen DK, So YT, Fisher RS, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2005 Sep 13:65(5):668-75 [PubMed PMID: 16157897]
Di Tanna GL, Porter JK, Lipton RB, Brennan A, Palmer S, Hatswell AJ, Sapra S, Villa G. Migraine day frequency in migraine prevention: longitudinal modelling approaches. BMC medical research methodology. 2019 Jan 23:19(1):20. doi: 10.1186/s12874-019-0664-5. Epub 2019 Jan 23 [PubMed PMID: 30674285]
Lampl C, MaassenVanDenBrink A, Deligianni CI, Gil-Gouveia R, Jassal T, Sanchez-Del-Rio M, Reuter U, Uluduz D, Versijpt J, Zeraatkar D, Sacco S. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. The journal of headache and pain. 2023 May 19:24(1):56. doi: 10.1186/s10194-023-01594-1. Epub 2023 May 19 [PubMed PMID: 37208596]
Level 1 (high-level) evidenceMirza N, Marson AG, Pirmohamed M. Effect of topiramate on acid-base balance: extent, mechanism and effects. British journal of clinical pharmacology. 2009 Nov:68(5):655-61. doi: 10.1111/j.1365-2125.2009.03521.x. Epub [PubMed PMID: 19916989]
Wiśniewski M, Łukasik-Głebocka M, Anand JS. Acute topiramate overdose--clinical manifestations. Clinical toxicology (Philadelphia, Pa.). 2009 Apr:47(4):317-20. doi: 10.1080/15563650601117954. Epub [PubMed PMID: 19514879]
. 2023 ACMT Annual Scientific Meeting Abstracts - San Diego, CA. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2023 Mar 23:19(2):63-168. doi: 10.1007/s13181-023-00930-w. Epub 2023 Mar 23 [PubMed PMID: 36952114]
Cheng CM, Salazar A, Amato MG, Lambert BL, Volk LA, Schiff GD. Using drug knowledgebase information to distinguish between look-alike-sound-alike drugs. Journal of the American Medical Informatics Association : JAMIA. 2018 Jul 1:25(7):872-884. doi: 10.1093/jamia/ocy043. Epub [PubMed PMID: 29800453]