Lamotrigine in bipolar disorder: preventing depression to treat the disease

PURPOSE: The aim of this paper is to critically ascertain the effectiveness of lamotrigine (LTG) as a key strategy for the treatment of bipolar I disorder. METHODS: PubMed and Cochrane Library databases were searched using the following keywords: "lamotrigine" AND "bipolar disorder", "psychotic" or "mood disorder". RESULTS: Lamotrigine, has shown significant efficacy in preventing or delaying the onset of depressive episodes in bipolar disease. The standard final dose is 200 mg/day to be achieved with slow titration. The concomitant use of LTG and valproic acid requires a reduction of the standard final dosage of LTG to 100 mg/day in order to prevent the occurrence of adverse reactions, while an increase in the dosage of LTG (up to a maximum of 400 mg/day) is required in the case of concomitant use of enzyme inducers, such as carbamazepine. Lamotrigine is well tolerated and has a relatively low risk of side effects. Slow titration and accurate monitoring in the first weeks of treatment are necessary in order to reduce the risk of adverse events, such as severe skin rash, whose onset is however rare in the adult population (0.1%). It is possible to use LTG during pregnancy, breastfeeding or in subjects with liver or kidney disorders, following a preliminary assessment of the risk-benefit ratio. CONCLUSIONS: Lamotrigine is suitable for preventing or delaying the onset of depressive episodes in patients with bipolar I disorder, and has a high level of tolerability. Prevention of depression determines stabilization of bipolar disease and may contribute to a better overall outcome in patients with predominantly depressive episodes. In patients with a clinical history characterized by severe and repeated manic episodes, it is advisable to combine LTG with an antimanic agent (e.g. lithium or second generation antipsychotic) even in the maintenance phase. Lamotrigine is a valid therapeutic option in the long-term prevention and stabilization of the depressive phases in patients with bipolar I disorder.