Mixed states in bipolar disorders : a review of current therapeutic strategies

Mixed states are characterized by the mixture or rapid alternation, within hours, of manic and depressive symptoms. They bear a high suicidal risk and therefore represent a major therapeutic issue. We performed a computerized bibliographic search and reviewed the efficacy of the available treatments of mixed states. It confirmed the recognized poor efficacy of lithium and the need to discontinue antidepressants. Among mood stabilizers, divalproate and its derivatives are those with the highest level of evidence. As regards new anticonvulsants, the data are yet too limited to recommend them as first line treatments. They may however be used as second line or adjunct treatments in case a monotherapy with a reference treatment has failed. Among antipsychotic drugs, clozapine has demonstrated its efficacy but also remains a second line treatment due to its high risk of neutropenia and agranulocytosis. Electroconvulsive therapy is a useful alternative in treatment resistant cases or when there is an imminent risk for suicide. Some degree of uncertainty remains for the treatment of the so called, agitated depressions, as no study has yet focused on this issue with a specifically selected sample of patients. Such a study would also enlighten the uncertain nosological status of this clinical entity and would answer as to whether they belong to the category of mixed states.