Lamotrigine: when and where does it act in affective disorders? A systematic review

Recent published data and treatment guidelines have created uncertainty about the use of lamotrigine in affective disorders, especially in acute bipolar depression. Furthermore, unpublished data on lamotrigine in mania, mixed episodes, unipolar depression and rapid cycling are still waiting to be integrated into the literature. Therefore, we critically reviewed the position of lamotrigine in the acute and long-term treatment of affective disorders. Studies were identified by searching English language articles published in MEDLINE using the key words: lamotrigine, bipolar depression, unipolar depression, mania, mixed episode, long-term treatment, rapid-cycling. Results of unpublished trials were obtained from the GlaxoSmithKline website. Lamotrigine showed efficacy in the prophylaxis of bipolar disorder, more so in depressive than manic episodes. There was no evidence of effectiveness in the acute treatment of mania, mixed episodes, unipolar depression or rapid-cycling bipolar I disorder. Its effect in the acute treatment of bipolar depression is at most small. Based on current evidence, lamotrigine is indicated for the prophylaxis of bipolar disorder with predominantly depressive episodes. Its effectiveness in the acute treatment of bipolar depression is open to debate, and practical considerations limit its usefulness here. There are no grounds for recommending its use in manic or mixed states, in rapidly-cycling bipolar I or in unipolar depression.