Lithium and valproate in manic and mixed states: a naturalistic prospective study

Objectives Lithium is still recommended as a first-choice treatment for acute bipolar mania, especially in pure euphoric mania of mild to moderate severity. Despite the large quantity of evidence supporting the efficacy of lithium, in clinical practice its use has often been limited because of management issues related to its narrow therapeutic index. International guidelines suggest combining lithium with a second mood stabilizer (anticonvulsant or atypical antipsychotic) for treatment of mixed states, rapid cycling and severe forms of mania with atypical features, which are classically considered to be poorly responsive to lithium alone. To date, however, the specific modalities of these associations on the basis of different clinical presentations have been poorly investigated in clinical trials. In this study, we aimed to evaluate the modalities of use of lithium in a naturalistic setting of manic and mixed bipolar patients, and to investigate the effects of its combination with valproate on the clinical course.