Anticonvulsants/Anti-epileptics For Neuropathy

Today's post from painhq.org (see link below) looks at the main anticonvulsants or anti-epileptic drugs that are prescribed for neuropathic pain. Many people are prescribed anti-convulsants after other pain killers and anti-depressive drugs have failed and many wonder why. The implications of being prescribed drugs that are essentially meant for a totally different condition, can be alarming, so this sort of article is useful in explaining which drugs are involved and what they do. If you are prescribed an anti-convulsant, it's also worthwhile discussing any possible side effects with your doctor, so that you're fully aware of any future complications.

What are Anticonvulsants?

Anticonvulsants are a group of drugs that were designed to help manage seizures, but have since been used in the treatment and management of neuropathic pain. It is a fairly large and diverse family of drugs, sometimes referred to as ‘anti-seizure medications’ or ‘antiepileptics’. These drugs are thought to work through a number of different mechanisms: some may block different neurotransmitters; others may affect nerve signalling and ‘firing’ through binding to different receptors; altering ion channels in the brain; or ‘stabilizing’ some of the nerve cell membranes to ‘quiet’ pain signalling. On balance, it is thought that through these various mechanisms anticonvulsants affect pain communication pathways for patients with neuropathic pain.

How do they work?

Anticonvulsants were first used in pain management because it was thought that the nature of pain was somewhat similar to that of epileptic seizures – too much nerve cell firing. A number of these drugs have been shown to block the signals from damaged neurons which would normally communicate pain within the body.

What kinds are there?

Gabapentin (Neurontin): Gabapentin works by binding to the calcium channels in neurons. These calcium channels help communicate pain within the body and, when blocked, help to dull the signal. Gabapentin is one of the only drugs used to treat neuropathic pain that is solely metabolized through the kidney (most are metabolized through the liver). It is considered one of the ‘first line’ medication treatments for most neuropathic pain syndromes. It is often used for treating post-herpetic neuralgia and diabetic neuropathy. 

Pregabalin (Lyrica): Developed as a more potent follow-up to Gabapentin, Pregabalin has been prescribed for postherpetic neuralgia, diabetic peripheral neuropathy and central neuropathic pain. Pregabalin is also associated with a lower risk for dependency and potential abuse.

Carbamazepine (Tegretol) / Oxcarbazepine (Trileptal): Carbamazepine works by binding to sodium channels in neurons and limiting pain signals. Used It is frequently used to treat trigeminal neuralgia, but also diabetic neuropathy and potentially other forms of neuropathic pain (though more research is necessary). 

Valproate (Sodium valproate, valproic acid): Valproate helps block calcium channels and increases the levels of GABA in the brain. The calcium channels help to communicate pain while GABA helps to black dull pain signals in the brain by blocking communication channels and affecting nerve transmission. More evidence is needed to determine the use of Valproate in the treatment of neuropathic pain. 

Lamotrigine (Lamictal): Lamotrigine helps to block sodium channels and helps to regulate signals between neurons. Used it is sometimes used in the treatment of trigeminal neuralgia, diabetic neuropathy and central neuropathic pain. There are increased risks of side effects in woman using Lamotrigine, which also poses certain risks for pregnancies.

Topiramate (Topamax): Topiramate has a number of mechanisms of action including sodium channels, calcium channels, GABA receptors, AMPA receptors and carbonic anhydrases. More evidence is needed to determine the use of Topiramate in the treatment of neuropathic pain.

Levetiracetam (Keppra): Levetiracetam works by binding to calcium channels in neurons, though it’s mechanisms aren’t fully understood. It can be used in the treatment of peripheral neuropathic pain. 

Lacosamide (Vimpat): Lacosamide works by binding to sodium channels in neurons, which prevents them from firing. Lacosamide also targets the cell which have been active for a longer period of time; in other words, damaged, over-active nerve cells that are sending pain signals (versus healthy cells). Lacosamide is used in the treatment of diabetic peripheral neuropathy.

Related evidence

Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012 Feb 15;2:CD009318. doi: 10.1002/14651858.CD009318.pub2.

Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007076. DOI: 10.1002/14651858.CD007076.pub2

Moore R, Wiffen PJ, Derry S, Toelle T, Rice AS C. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD007938. DOI: 10.1002/14651858.CD007938.pub3

Price MJ. Levetiracetam in the treatment of neuropathic pain: three case studies. Clin J Pain. 2004 Jan-Feb;20(1):33-6.

Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice AS, Lunn MP, Hamunen K, Haanpaa M, Kalso EA. Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013 Nov 11;11:CD010567. doi: 10.1002/14651858.CD010567.pub2.

Wiffen PJ, Derry S, Lunn MPT, Moore R. Topiramate for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD008314. DOI: 10.1002/14651858.CD008314.pub3

 http://www.painhq.org/learning/knowledge-base/category/treatments/traditional-medicine-and-surgery/anticonvulsants