Lamotrigine-induced mania: warning report for the identification of vulnerable populations and expert clinical recommendations for prescription.

Lamotrigine (LTG) is an anticonvulsant drug used for the prevention of depressive episodes in bipolar disorder (BD) that might induce manic episodes in some cases. A 38-year-old man, stabilized with asenapine due to a brief psychotic episode, presented depressive symptoms and LTG was titrated up to 200 mg/day in 6 weeks. One week later he was diagnosed with a first manic episode with psychotic symptoms [Young Mania Rating Scale (YMRS = 31)] and type I BD (BD-I). LTG was withdrawn and he was treated with lithium and lurasidone. The episode remitted in 1 week. A 45-year-old woman with BD presented persistent depressive symptoms and received LTG 25 mg/day. After 3 weeks she was diagnosed with a manic episode with psychotic symptoms (YMRS = 35). LTG was suspended and aripiprazole increased. The episode remitted within 10 days. Both patients remained euthymic with no further episodes after 1-year follow-up. The propensity of LTG to induce manic episodes may be related to its lack of antimanic effects, along with its antidepressant properties, probably related to decreased glutamate release. Secondary analyses from LTG randomized clinical trials have excluded subjects with higher vulnerability to manic switches so that the risk of LTG-induced mania might have been underestimated. LTG-induced mania may be more likely to happen in patients with BD-I, manic predominant polarity, an index manic episode, or those with a history of the antidepressant manic switch. Therefore, in BD patients with the aforementioned risk factors, LTG use should be carefully managed: starting with low doses, extending tapering lengths, using adjunctive treatments and close monitoring manic symptoms.