Antiepileptic drugs lamotrigine

J Magdalou, R Herber, R Bidfault, G Siest. In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharm Exp Ther 260 1166, 1992. 

Danielsson BR, Lansdell K, Patmore L, Tomson T. Effects of the antiepileptic drugs lamotrigine, topiramate and gaba-pentin on hERG potassium currents. Epilepsy Res 2005 63(1) 17-25. 

Zaworotko and coworkers have also used animal pharmacokinetic (PK) studies to demonstrate how the PK profile of a poorly soluble antiepileptic drug, lamotrigine, can be altered significantly through the use of cocrystal formation. ... 

Turning to the pharmacotherapy for mania, for decades lithium was the only effective drug treatment. More recently, a number of antiepileptic drugs including carba maze pine, lamotrigine and valproate have been shown to also act as mood stabilisers and are becoming established for the treatment and prophylaxis of both unipolar mania and bipolar manic depressive disorders. 

In addition to these drugs, many of the newer antiepileptic drugs such as lamotrigine have found a place in the therapeutic management of mania. These are extensively covered in Chapter 12. 

The apparent clearance of lamotrigine is affected by the coadministration of AEDs. Lamotrigine is eliminated more rapidly in patients who have been taking hepatic enzyme inducing antiepileptic drugs (ElAEDs), including carbamazepine, phenytoin, phenobarbital, and primidone. 

Curry, W.J. and Kulling, D.L. (1998) Newer antiepileptic drugs ga-bapentin, lamotrigine, felbamate, topiramate and fosphenytoin. Am Fam Physician 57 513-520. 

Three antiepileptic drugs have now been FDA approved as mood stabilizers for the prevention of recurring episodes of mania divalproex sodium (Depakote), extended-release carbamazepine (Equetro), and lamotrigine (Lamictal). Many of these drugs are prescribed to children for the control of epilepsy and, increasingly, for bipolar disorder. A critical question is their effect on the developing mental and emotional function of children, but there is little research on the subject (Loring, 2005). 

Equetro (extended-release carbam-azepine antiepileptic drug) Lamictal (lamotrigine antiepileptic drug)... 

Should certain antiepileptic drugs be contraindicated in patients with active psychosis Unfortunately there is not enough solid information to answer this question. Undoubtedly, anticonvulsants that are less likely to cause psychosis (lamotrigine, carbamazepine, oxcarbaze-pine, valproate) should be preferred (52,53). However, patients with psychoses have been successfully treated even with drugs that are believed to be associated with psychosis, such as vigabatrin. For example, in a prospective study in 10 patients with psychosis and epilepsy to whom vigabatrin was added, there was no aggravation of the psychiatric disorder (54). 

Also, if concomitant enzyme-inducing antiepileptic drugs such as carbamazepine, phenobarbital, phenytoin, and primidone are discontinued after lamotrigine dose is stabilized, then the lamotrigine dose should be maintained for 1 week following discontinuation of the other drug and then reduced by half over 2 weeks in equal decrements each week... 

Enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenobarbital, phenytoin, primidone) may increase the clearance ot lamotrigine and lower its plasma levels... 

Clearance of tiagabine may be reduced and thus plasma levels increased if taken with a non-enzyme inducing antiepileptic drug (e.g., valproate, gabapentin, lamotrigine), so tiagabine dose may need to be reduced... 

The cost-effectiveness of four antiepileptic drugs used to treat newly diagnosed adult epilepsy has been studied by cost minimization analysis in 12 European countries (6). The analysis took account of each drug s adverse effects and tolerability profiles. Lamotrigine incurred higher costs than carbamazepine, phenytoin, and valproate, whose costs were similar. 

The use of antiepileptic drugs (gabapentin, lamotrigine, and topiramate) as mood stabilizers has been... 

Pseudolymphoma and a condition resembling malignant lymphoma occur very rarely with phenytoin (SED-13, 142). There is no evidence of a significant increase in the incidence of other tumors. There have also been reports of pseudolymphoma with other antiepileptic drugs, including carbamazepine (147-149), lamotrigine (150), phenobarbital (151), and valproic acid (151). 

Pharmacodynamic interactions also occur. In particular, the adverse effects of any drug can be increased by other drugs with similar properties. One example is the reciprocal potentiation of the neurotoxic effects of carbamazepine and lamotrigine in patients taking a combination of these drugs (180). Some drugs (for example ciclosporin, clozapine) have a proconvulsant effect and can reduce the efficacy of antiepileptic drugs. 

Lamotrigine has been stndied in 32 children with epilepsy refractory for at least 1 year to other antiepileptic drugs (7). Adverse effects were uncommon, and there were no skin rashes. 

The effects of other antiepileptic drugs on the pharmacokinetics of lamotrigine have been studied in 62 patients with epilepsy (71). Carbamazepine, phenytoin, and phenobarbital, all enzjme inducers, increased the oral clearance of lamotrigine, individually by 58% and in combination by nearly 200%. 

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