Patients with multiple sclerosis show higher prevalence of psychiatric disorders compared to general population, that are hardly managed by pharmacotherapy. In the present report a female patient, 44 years old, with diagnosis (according to DSM-IV) of 340 multiple sclerosis, 296.32 major depressive disorder, recurrent, moderate, 292.84 antidepressant-induced mood disorder, with manic features, is described. In this patient depressive symptoms did not respond to a number of drugs, including tricyclic antidepressants, selective serotonine re-uptake inhibitors hand lithium. Moreover, she had hypomanic and manic episodes induced by two different antidepressant, hydroxy-tryptophan and clorimipramine. Until today, only amisulpride (50 mg/die for four months, then 50 mg every two days for two months) has shown a significant effect on depressive symptomatology, moreover, this drug has not induced the occurrence of manic symptoms.