Lamotrigine indications

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

Use standard therapeutic serum concentration ranges if clinically indicated if partial response or breakthrough episode, adjust dose to achieve higher serum concentrations without causing intolerable adverse effects valproate is preferred over lithium for mixed episodes and rapid cycling lithium and/or lamotrigine is preferred over valproate for bipolar depression. 

Lactation Preliminary data indicate that lamotrigine passes into breast milk. Breast-feeding while taking lamotrigine is not recommended. 

Children Lamotrigine is indicated as adjunctive therapy for partial seizures in patients above 2 years of age and for the generalized seizures of Lennox-Gastaut syndrome. Safety and efficacy for other uses in patients younger than 16 years of age have not been established. Safety and efficacy in patients below the age of 18 years with bipolar disorder have not been established. 

Lamotrigine has a broad spectrum of action and is effective in generalized and partial epilepsies. Its primary mechanism of action appears to be blockage of voltage-dependent sodium channels, although its effectiveness against absence seizures indicates that additional mechanisms may be active. Lamotrigine is almost completely... 

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

ECT should be considered for more severe forms of depression (e.g., those associated with melancholic and psychotic features, particularly when the patient exhibits an increased risk for self-injurious behavior) or when there is a past, well-documented history of nonresponse or intolerance to pharmacological intervention. Limited data indicate that bipolar depressed patients may be at risk for a switch to mania when given a standard TCA. A mood stabilizer alone (i.e., lithium, valproate, carbamazepine, lamotrigine), or in combination with an antidepressant, may be the strategy of choice in these patients. Some elderly patients and those with acquired immunodeficiency syndrome may also benefit from low doses of a psychostimulant only (e.g., methylphenidate) (see also Chapter 14, The HIV-Infected Patient ). Fig. 7-1 summarizes the strategy for a patient whose depressive episode is insufficiently responsive to standard therapies. 

These early trials indicate a possible bimodal therapeutic effect with lamotrigine for both the manic and depressed phases. Low starting doses and slow titration are required, however, due to the increased risk of rash (approximately 10%), of which 1% may be more severe and possibly life-threatening ( 233), limiting this agent s use for acute episodes. 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Vigabactin is indicated for second-line use in patients with refractory partial epilepsy but, unlike lamotrigine and topiramate, it does not appear to be useful in generalized epilepsies. It is the drug of choice for infantile spasms. 

Figure 6.12. Selected anticonvulsants for the development of a pharmacophore model. The essential structural elements are indicated by dotted rectangles. 1 = phenytoin 2 = carbamazepine 11 = lamotrigine 13 = zonisamide 60 = rufinamide inset, 58 = remacemide. R, hydrophobic unit D, electron-donor group HAD, hydrogen donor/acceptor unit. (AfterRef 281.)...

Table IV-1 -3 summarizes the mechanisms, indications for use, and potential toxic effects of some i newer anticonvulsants. Those listed are felbamate, gabapentin, lamotrigine, tiagabine, topiramate, and j...

Lamotrigine is a 5-phenyl-1,2,4-triazine derivative indicated as monotherapy or as an adjunct for partiai seizures in aduits, as adjunct in patients with Lennox-Gastaut syndrome, and as adjunct for partiai seizures in chiidren 2 years of age and oider. Lamotrigine may have additionai benefit in combating myocionic and typicai absence seizures, it is approved for use in the maintenance treatment of bipoiar disorder. 

Clonazepam and valproate commonly are used to control myoclonic seizures. Studies suggest that lamotrigine and topiramate may be effective as well, although neither is approved by the U.S. FDA for this indication. 

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