Lamotrigine efficacy

Froscher W, Keller F, Kraemer G, Vogt H. Serum level monitoring in assessing lamotrigine efficacy and toxicity. Epilepsia 1999 40(Suppl 2) 252. 

Jozwiak S, Terczynski A. Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy. Seizure 2000 9(7) 486-92. 

The pharmacokinetic interaction would appear to be established however, since the relationship between lamotrigine levels and efficacy is not clear, the clinical relevance of the decrease is uncertain. Lamotrigine efficacy should be monitored in patients taking lopinavir/ritonavir, and probably any ritonavir-boosted regimen. Anticipate the need to increase the lamotrigine dose. 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

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. 

The use of lamotrigine, gabapentin, or topiramate in children (especially those younger than 16 years of age) cannot be endorsed at the present time as first-line therapy until additional safety and efficacy data are available. However, with careful evaluation of the rislc/ben-efit ratio, they could be considered in adolescents older than 16 years of age with BD, refractory to other standard interventions. 

Matsuo, R, Bergen, D., Faught, E., Messenheimer, J.A., Dren, A.T, Rudd, G.D., and Lineberry, C.G. (1993) Placebo-controlled study of the efficacy and safety of lamottigine in patients with partial seizutes. U.S. Lamotrigine Protocol 0.5 Clinical Trial Group. Neurology 43 2284-2291. 

Uvebrant, P., and Bauziene, R. (1994) Intractable epilepsy in children the efficacy of lamotrigine treatment, including non-seizure-related benefits. Neuropediatrics 25 284—289. 

Well known for their clinical role as antimanic agents, anticonvulsants such as carbamazepine and valproate have also been used in both bipolar and unipolar TRD (Post et al. 1994a, 1994b). In one series. Post et al. (1994a) found a greater response in patients with bipolar (15/40) versus those with unipolar (2/17) TRD. Open studies of valproate also suggest limited antidepressant efficacy, but only a paucity of data with anticonvulsants on TRD exists. More recently, in open trials, lamotrigine (a partial anticonvulsant that inhibits glu-... 

Manji HK, Chen G, Hsiao JK, et al Regulation of signal transduction pathways by mood-stabilizing agents implications for the delayed onset of therapeutic efficacy. J Clin Psychiatry 57 (suppl 13) 34 6, 1996 Marangell LB, Martinez JM, Ketter TA, et al Lamotrigine treatment of bipolar disorder data from the first 500 patients in STEP-BD. Bipolar Disord 6 139-143, 2004... 

Lamotrigine, another anticonvulsant, has been shown to be a potentially good mood stabilizer with both antidepressant and antimanic efficacy (Fatemi et ul., 1997 Calabrese et al., 1999). 

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). 

In a double-blind comparison of lamotrigine versus desipramine or placebo, 450 unipolar depressed patients were studied. Lamotrigine was found to be significantly better than placebo, with desipramine falling between lamotrigine and placebo in terms of efficacy. 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

Several other therapeutic effects of sodium channel blockers have been suggested. Most of these stem from clinical activities of approved anticonvulsants and antiarrhythmics with sodium channel blocking activity. Beneficial effects of sodium channel blockers for the treatment of bipolar disease are suggested by clinical data with lamotrigine [63-67], phenytoin [68], topiramate [69], and carbamazepine [70,71]. In addition, clinical studies with lidocaine suggest efficacy in the treatment of tinnitus [72] and, as an inhaled formulation, in the suppression of cough [73,74]. 

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. 

Misperceptions about gabapentin s efficacy in bipolar disorder have led to its use in more patients than other agents with proven efficacy, such as lamotrigine Off-label use as an adjunct for schizophrenia may not be justified May be useful for some patients in alcohol withdrawal... 

Lamotrigine is another glutamate release inhibitor that has been studied in neurodegenerative diseases. In ALS, 300mg of lamotrigine per day had no effect when compared to placebo in a small number of patients (Ryberg et al, 2003). Lamotrigine also failed to show symptomatic benefit in patients with PD (Shinotoh et al., 1997), but neither study had adequate power to truly assess efficacy. 

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. 

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