To report two cases of major depressive disorder in which lamotrigine (LTG) induced anger with murderous impulse.

Case 1 was a 22-year-old man with symptoms of obsessive–compulsive disorder who developed major depressive disorder with antidepressant-induced hypomanic episodes. Case 2 was a 23-year-old woman experiencing an antidepressant-refractory depressive episode for whom remission was achieved by switching to a mood stabilizer and antipsychotics. In both cases LTG was started to treat the depressive episode.

Case 1 manifested with anger and murderous impulse when taking 125 mg/day of LTG. A reduction to 75 mg/day calmed this anger. Case 2 manifested with the same symptom when taking 25 mg/day of LTG, and the symptom immediately disappeared upon stopping LTG.

Use of LTG for epilepsy in intellectually disabled patients was reported to be associated with onset or exacerbation of aggressive or violent behavior. The two cases would suggest that LTG may cause anger so severe as to be accompanied with murderous impulse when administered to patients with mood disorders. Physicians should be cognizant of this possible, albeit infrequent, adverse effect even in use of LTG for mood disorders.