Topiramate, sold under the brand name Topamax among others, is a medication used to treat epilepsy and prevent migraines.[ It has also been used for alcohol dependence and essential tremor.][ It is taken orally (by mouth).][
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Common side effects include paresthesia, feeling tired, loss of appetite, abdominal pain, weight loss,[ Topiramate can cause birth defects, including cleft lip and palate.][
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Topiramate was approved for medical use in the United States in 1996.[ It is available as a generic medication.]
Medical uses
Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant.
Pain
A 2018 review found topiramate of no use in chronic low back pain.
Other
One common off-label use for topiramate is in the treatment of bipolar disorder.
Topiramate has been used as a treatment for alcoholism.
Other uses include treatment of obesity
Adverse effects
People taking topiramate should be aware of the following risks:
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Avoid activities requiring mental alertness and coordination until drug effects are realized.
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Topiramate may impair heat regulation,
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Topiramate may cause visual field defects.
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Topiramate may decrease the effectiveness of oestrogen-containing oral contraceptives.
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Taking topiramate in the first trimester of pregnancy may increase the risk of cleft lip/cleft palate in infants.
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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.
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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.
Frequency
Adverse effects by incidence:
Very common (>10% incidence) adverse effects include:
Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.
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.
Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.
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 suicide,
Overdose
Symptoms of acute and acute on chronic exposure to topiramate range from asymptomatic to status epilepticus, including in patients with no seizure history.[ Topiramate has been deemed the primary substance that led to fatal overdoses in cases that were complicated by polydrug exposure.][
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Interactions
Topiramate has many drug-drug interactions. Some of the most common are listed below:
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As topiramate inhibits carbonic anhydrase, use with other inhibitors of carbonic anhydrase (e.g. acetazolamide) increases the risk of kidney stones.
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(e.g. carbamazepine) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.
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Topiramate may increase the plasma levels of phenytoin.
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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.
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Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure.
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As topiramate may result in acidosis, other treatments that also do so may worsen this effect.
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Anhidrosis and hyperthermia were reported in post-marketing reports about topiramate; antimuscarinic drugs (like trospium) can aggravate these disorders.
Pharmacology
The topiramate molecule is a sulfamic acid 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.
Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.
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.
While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is one of the very few anticonvulsants that do not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.
Detection in body fluids
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.
History
Topiramate was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceuticals.
Research
Topiramate is being studied as a potential treatment for post-traumatic stress disorder (PTSD).
There is some evidence for the use of topiramate in the management of cravings related to withdrawal from dextromethorphan.
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.
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