Lamotrigine side effects

One unwanted side-effect of phenytoin is its anti-folate activity. A programme of synthetic chemistry to manipulate the structure of the anti-folate compound pyri-methium to try to replace that property with anticonvulsant activity resulted in the synthesis of lamotrigine. It proved to be an effective AED in partial and generalised epilepsy but experience has found it also to be of value in absence seizures. 

Studies suggest that as monotherapy for partial seizures, lamotrigine is as effective as carbamazepine and phenytoin lamotrigine may be better tolerated. Clinical data suggest that oxcarbazepine is as effective as phenytoin, valproic acid, and immediate-release carbamazepine, with perhaps fewer side effects. 

The newer AEDs were first approved as adjunctive therapy for patients with refractory partial seizures. To date, lamotrigine, topiramate, and oxcarbazepine have received FDA approval for use in monotherapy in patients with partial seizures. Felbamate has monotherapy approval but causes significant side effects. 

The most frequent side effects are diplopia, drowsiness, ataxia, and headache. Rashes are usually mild to moderate, but Stevens-Johnson reaction has also occurred. The incidence of the more serious rashes appears to be increased in patients who are also receiving valproic acid and who have rapid dosage titration. Valproic acid substantially inhibits the metabolism of lamotrigine. 

It is very important to choose medications with the least possibility of making an ill pediatric patient suffer additional morbidity from side effects to medication directed at mood or behavior. For these reasons, mood stabilizers such as lamotrigine (which carries with it the risk of a severely toxic rash) should be seen only as third- or fourth-line agents. 

Lamotrigine is well tolerated and is not associated with hepatotox-icity, weight gain, or significant sedation. Common early side effects include headache, dizziness, gastrointestinal distress, and blurred or double vision. The most serious potential side effect is rash (described in the following subsection). 

Side effects. The most common side effects are headache, nausea and vomiting, diplopia, dizziness, ataxia and tremor. There are also reports that lamotrigine can cause such psychiatric side effects as aggression, agitation, confusion, hallucinations and psychosis, some of these effects possibly being associated with a reduction in the glutamatergic system. Rashes are a frequent side effect, occurring in up to 5% of patients. Usually rashes are mild but occasionally can be severe and amount to a Stevens-Johnson syndrome. The severe rash occurs more commonly in children. 

Lathers CM, Schraeder PL, Claycamp HG. Clinical pharmacology of topiramate versus lamotrigine versus pheno-barbital comparison of efficacy and side effects using odds ratios. J Clin Pharmacol 2003 43 491-503. 

Lamotrigine is a potent inhibitor of dihydrofolate reductase. Folate concentrations are decreased when this drug is administered. If folate replacement is not implemented, rash and anemia may be experienced when lamotrigine is at its therapeutic concentration. Lamotrigine has also been associated with development of severe rash (Stevens-Johnson syndrome) in approximately 1% of patients receiving lamotrigine. These side effects are not drug concentration related. 

The traditional treatment of tonic-clonic seizures is phenytoin or phenobarbital however, the use of carbamazepine and valproic acid is increasing because these AEDs have a lower incidence of side effects and equal efficacy. Valproic acid generally is considered the drug of first choice for atonic seizures and for juvenile myoclonic epilepsy. Lamotrigine and perhaps topiramate and zonisamide may be alternative agents for these seizure types. 

Another barbiturate (phenobarbitone (Luminal)) and a newer drug lamotrigine (Lamictal) are used to treat epilepsy. Trazodone (Molipaxin) is a useful anti-depressant with fewer side-effects than some of the older drugs. The action of varenicline (Champix), used to treat smoking withdrawal, has a straightforward mechanism, being a nicotinic partial agonist. 

Clonazepam (Klonopin) was approved in 1975 for monotherapy or adjunctive treatment of akinetic (atonic), myoclonic, and absence variant seizures (64). Clonazepam also was found to be effective in controlling absence seizures, but because of the high incidence of side effects. It Is rated second to ethosuximide. It may be useful, however. In absence seizures when succinimide therapy has failed. It Is considered to be a third-line drug after 1) ethosuximide or valproate and 2) lamotrigine or valproate for the treatment of absence seizures. It is ineffective for treatment of generalized clonic-tonic seizures. 

Comparative studies Carbamazepine versus lamotrigine Carbamazepine and lamotrigine have been compared in 125 elderly patients with epilepsy using the modified Side Effect and Life Satisfaction Inventory and the Liverpool Adverse Event Profile in an international double-blind study [4 ]. Neither drug caused significant changes in health-related quality of life after 40 weeks. A borderline difference in the Side Effect and Life Satisfaction Inventory Dysphoria subscores favored lamotrigine. 

Lamotrigine (Lamictal ) is available as an oral regimen in 25 mg, 100 mg, 150 mg and 200 mg tablets. Only whole tablets are recommended for use and doses should be rounded down to the nearest whole tablet. It is recommended that Lamictal therapy be initiated at low doses and slowly escalated over the first 4 weeks of therapy to minimize adverse side effects such as skin rash (see Table 74.1). 

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