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Anticonvulsants / Anti-Seizure Medications


What are Anticonvulsants?

Anticonvulsants represent a diverse class of drugs indicated for the treatment of various types of seizures associated with seizure disorders such as epilepsy, a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain, and other disorders.

The first effective anticonvulsant was potassium bromide, introduced in 1857. In 1910, phenobarbital, which then was used to induce sleep, was found to have antiseizure activity and became the drug of choice for many years. In 1940, phenytoin was found to be an effective for the treatment of epilepsy. The last ten years of the 20th century were called in neuroscience "decade of the brain". This period has brought many new antiepileptic drugs: vigabatrin, lamotrigine, topiramate, tiagabine, gabapentin, oxcarbazepine, levetiracetam and zonisamide.

Classification

  • Aldehydes
  • Bromides
  • Barbiturates
    • Mephobarbital (Mebaral)
    • Pentobarbital (Nembutal)
    • Phenobarbital (Luminol, Solfoton)
  • Benzodiazepines
    • Chlorazepate (Tranxene)
    • Clonazepam (Klonopin)
    • Diazepam (Valium)
  • Carbamates
    • Felbamate
  • Fructose derivatives
    • Topiramate (Topamax)
  • GABA Analogues
    • Gabapentin (Neurontin)
    • Pregabalin (Lyrica)
    • Tiagabine (Gabitril)
  • Hydantoins
    • Ethotoin (Peganone)
    • Fosphentyoin (Mesantoin)
    • Phenytoin (Dilantin)
  • Carboxamides (Oxazolidinediones)
    • Carbamazepine (Carbatrol, Tegretol)
    • Oxcarbazepine (Trileptal)
  • Phenyltriazines
    • Lamotrigine (Lamictal)
  • Pyrrolidines
    • Levetiracetam (Keppra)
  • Succinimides
    • Ethosuximide (Zarontin)
    • Methsuximide (Celontin)
    • Phensuximide (Milontin)
  • Miscellaneous
    • Acetazolamide (Diamox)
    • Felbamate (Felbatol)
    • Primidone (Mysoline)
    • Valproic acid (Depakene, Depakote)
    • Zonisamide (Zonegran)

How do Anticonvulsants work?

Anticonvulsants have different mechanisms of action on neuronal function, but they have the common property of functional blockade of voltage-gated Na+ channels.

Anticonvulsants depress abnormal neuronal discharges in the CNS that may result in seizures. They may work by preventing the spread of seizure activity, depressing the motor cortex, raising seizure threshold, or altering levels of neurotransmitters, depending on the type.

Anti-seizure medications are used as monotherapy or in combination with other medications depending on the medical condition.

Anticonvulsants for Bipolar Disorder

Anticonvulsants seem to act as mood stabilizers and may enhance the action of atypical antipsychotics. They help to even the highs and lows of mood to people suffering from bipolar disorder (manic depression).

At first, they were prescribed only for people who did not respond to lithium. Today, they are often taken alone, with lithium, or with an antipsychotic drug to control mania.

Anticonvulsants used to treat bipolar disorder include 6:

  • Divalproex sodium, valproic acid, or valproate sodium (Depakote, Depakene) - useful for acute mania, recommended first-line treatment in bipolar I with rapid cycling.
  • Carbamazepine (Tegretol) - useful for acute mania
  • Lamotrigine (Lamictal) - useful for bipolar depression, bipolar II with rapid cycling; does not trigger manic/hypomanic switches.
  • Oxcarbazepine (Trileptal) - sometimes used for acute episodes in bipolar disorder, but its efficacy is not well studied5.

Anticonvulsants for Pain management

Anticonvulsants have been used in pain management since the 1960s. They are effective mainly for neuropathic pain chronic syndromes like trigeminal neuralgia, diabetic neuropathy, and for migraine prophylaxis 2.

Carbamazepine was the first of anticonvulsants to be studied in clinical trials and has been longest in use for neuropathic pain. Clinical trial data support its use in treating trigeminal neuralgia, but data for treatment of painful diabetic neuropathy are less convincing.

Oxcarbazepine is used for trigeminal neuralgia and painful diabetic neuropathy.

Gabapentin is the most widely used anticinvulsant for the treatment of neuropathic pain, specifically for painful diabetic neuropathy and postherpetic neuralgia. This drug also reduces postoperative pain.

More information on Gabapentin for pain conditions

Pregabalin is very effective for neuropathic pain and fibromyalgia 7. Pregabalin also has utility in the management of pre-operative and post-operative pain.

Lamotrigine has been reported to be effective in relieving pain from trigeminal neuralgia refractory to other treatments, and central post-stroke pain.

Results from clinical trials of phenytoin are equivocal. Zonisamide's mechanisms of action suggest that it would be effective in controlling neuropathic pain symptoms. Other anticonvulsants, including lorazepam, valproate, topiramate, and tiagabine, have also been under investigation. Anecdotal experience provides support for oxcarbazepine and levetiracetam 4.

Several recent clinical trials have shown that anticonvulsants may reduce spontaneous and movement-evoked pain. Some early findings suggest further that anticonvulsant drugs may alleviate postoperative anxiety, accelerate postoperative functional recovery and reduce chronic postsurgical pain 1.

Anticonvulsants for Migraine

Anticonvulsant drugs seem to be useful for the prophylaxis of migraine. This might be explained by a variety of actions of these drugs in the central nervous system that are probably relevant to the pathophysiology of migraine. Anticonvulsants that have demonstrated their efficacy in clinical trials are divalproex sodium, topiramate, sodium valproate, gabapentin, carbamazepine. Topiramate is the only anticonvulsant approved by the FDA for migraine prophylaxis. Neither clonazepam nor lamotrigine was superior to placebo in the studies. 3

More information on Topiramate for weight loss

References

  • 1. Gilron I. The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective. Can J Anaesth. 2006 Jun;53(6):562-71.
  • 2. Tremont-Lukats IW, Megeff C, Backonja MM. Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. Drugs. 2000 Nov;60(5):1029-52.
  • 3. Shahien R, Beiruti K. Preventive agents for migraine: focus on the antiepileptic drugs. J Cent Nerv Syst Dis. 2012 Feb 26;4:37-49. PubMed
  • 4. Wiffen PJ, Derry S, Moore RA, Lunn MP. Levetiracetam for neuropathic pain in adults. Cochrane Database Syst Rev. 2014 Jul 7;(7):CD010943 PubMed
  • 5. Vasudev A, Macritchie K, Vasudev K, Watson S, Geddes J, Young AH. Oxcarbazepine for acute affective episodes in bipolar disorder. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD004857. PubMed
  • 6. Singh V, Muzina DJ, Calabrese JR. Anticonvulsants in bipolar disorder. Psychiatr Clin North Am. 2005 Jun;28(2):301-23. PubMed
  • 7. Verma V, Singh N, Singh Jaggi A. Pregabalin in neuropathic pain: evidences and possible mechanisms. Curr Neuropharmacol. 2014 Jan.

By HealthyStock Research Group, September 2009
Medical resources reviewed: August 2018


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