Bipolar disorder is a common, severe, long-term condition, characterized by manic/hypomanic, depressed, or mixed states

1. (1) Lithium is the traditional treatment option, and valproate and carbamazepine have been introduced to better treat and stabilize manic/depressive cyclicity. Recently antipsychotics turned into a broader therapeutic option for bipolar disorder, as both alternative and adjunct to traditional mood stabilizers.

2. (2) Asenapine is an atypical antipsychotic indicated for the treatment of schizophrenia and of the manic or mixed episodes in bipolar I disorder (1,3). “Mrs. O.M.”, is a caucasian woman aged 55 suffering from bipolar disorder type I since she was 22 years old, with mood cycles characterized by long manic episodes with soft mixed and cognitive features. Readmitted for a manic exacerbation, the increasing of clozapine up to 250 mg/day was accompanied by hyperphagia, weight gain, cognitive impairment, sedation, fatigue, anergy, resistant chronic constipation. To that point clozapine was abruptly replaced with asenapine 20 mg/day with rapid clinical improvement within two days without major side effects. After 6 months the patient is still showing a good affective stability, without side effects. Our case report underlines the possibility of rapid switch from clozapine to asenapine in bipolar I disorder therapy resistant manic patients, presenting extrapyramidal, cognitive and metabolic side effects with atypical and typical neuroleptics.