Lamotrigine effects

Ryberg H, Askmark H, Persson L (2003) A double blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine Effects on CSE glutamate, aspartate, branched chain amino acid levels and clinical parameters. Acta Neurol Scand 108 1-8. 

Na+ channels at clinically relevant concentrations (carbamazepine, phenytoin, lamotrigine). Most of these anticonvulsant dtugs display three distinct effects on Na+ channels ... 

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

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. 

Calabresi, P, Centonze, D, Marfia, GA, Pisani, A and Bernardi, G (1999) An in vitro electro-physiological study on the effects of phenytoin, lamotrigine and gabapentia on striatal neurons. Brit. J. Pharmacol. 126 689-696. 

Lamotrigine is not approved for the acute treatment of depression, and the dose must be started low and slowly titrated up to decrease adverse effects if used for maintenance therapy of bipolar I disorder. A drug interaction and a severe dermatologic rash may occur when lamotrigine is combined with valproate (i.e., lamotrigine doses must be halved from standard dosing titration). 

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Mechanism of Action The mechanism of action of lamotrigine appears to involve blockage of ion channels and effects on glutamate transmission, although the precise mechanism in bipolar disorder is not clear.33... 

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. 

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. 

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. 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

Lamotngine (Lamictal). Lamotrigine, another anticonvulsant used to treat BPAD, is currently FDA approved for the prevention of both depressive and manic episodes during BPAD maintenance therapy. This represents a shift in the paradigms for BPAD therapy, as medications used to treat acute episodes have also typically been used for antimanic prophylaxis. Lamotrigine is not effective in the acute treatment of mania but has become for many the drug of choice for bipolar depression as well as for prevention of subsequent mood episodes of either polarity. 

Recently, other medications have been evaluated as mood stabilizers. This includes gabapentin (Neurontin), lamotrigine (Lamictal), and topiramate (Topamax). Only lamotrigine has been shown in controlled trials to be effective in the treatment... 

Coadministration with other hormonal contraceptive preparations or hormone replacement therapy Although the effect of other hormonal contraceptive preparations or replacement therapy on the pharmacokinetics of lamotrigine has not been evaluated, the effect may be similar to oral contraceptives. Therefore, similar adjustments to the dosage of lamotrigine may be needed. 

Nonteratogenic effects - There have been reports of decreased lamotrigine concentrations during pregnancy and restoration of prepartum concentrations after delivery. Dosage adjustments may be necessary to maintain clinical response. 

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