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A to Z of MS Lamotrigine (Lamictal)

Product name

Lamictal

Lamotrigine is an anti-epileptic drug that has been used experimentally in multiple sclerosis to reduce the pain associated with trigeminal neuralgia and spasticity. Lamotrigine is not currently recommended in the NICE Guidelines for the treatment of pain in MS.

Lamotrigine has been studied in a phase II clinical trial to see if it can help stop further damage to the nerve cells (an approach known as neuroprotection), and therefore prevent the further accumulation of disability, in a group of people with secondary progressive MS. 120 people were randomly assigned to receive a target dose of 400mg/day of lamotrigine or placebo for two years. The primary measure used in the trial was the rate of change in the volume of the central area of the brain (known as the partial cerebral volume). In the first year of the study lamotrigine treatment appeared to be associated with greater partial (central) cerebral volume loss than treatment with placebo. This early volume loss reversed partially on discontinuation of treatment with lamotrigine and over 24 months the effect of lamotrigine on cerebral volume did not differ from that of placebo. Lamotrigine treatment reduced the deterioration of the timed 25-foot walk, but did not affect other secondary clinical outcome measures. More patients in the lamotrigine group than the placebo group experienced a rash and dose-related deterioration of gait and balance.

The researchers concluded that future trials of neuroprotection in MS should include investigation of complex early volume changes in different areas of the central nervous system (brain and spinal cord), effects unrelated to neurodegeneration and targeting of earlier and more inflammatory disease.

A phase II clinical trial to study the neuroprotective effects of lamotrigine in combination with interferon beta 1a (Avonex) in people with relapsing remitting MS is currently recruiting participants in Switzerland. This study is expected to conclude in 2011.

How lamotrigine works

Lamotrigine is a type of anticonvulsant drug that acts by blocking sodium channels, thereby reducing or blocking some messages from the brain to the rest of the body. Inflammation leads to increased levels of nitric acid and sodium in the body, both of which can damage nerve cells. It is because of lamotrigine's effect on regulating the chemical processes within nerves, that it is being studied to see if it has a neuroprotective effect.

How lamotrigine is given

Lamotrigine is given orally as tablets for the treatment of pain. Experimental doses range from 25-400mg per day. People start on a low dose that is gradually increased.

Side effects and contraindications

Side effects include rash, headache, stomach upsets, double vision, dizziness and ataxia (problems with coordination). Lamotrigine can stop some types of oral contraceptive pill from working, so this should be taken into account.

References

Breuer B, et al.
A randomized, double-blind, placebo-controlled, two-period, crossover, pilot trial of lamotrigine in patients with central pain due to multiple sclerosis.
Clinical Therapeutics 2007;29(9):2022-2030.
abstract

Kapoor R, et al.
Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial.
Lancet Neurology 2010;9(7):681-688.
abstract