Abstract
Since decades, lithium and valproate remain the pharmacological cornerstone to treat bipolar disorder. Different response patterns occur according to the phases of illness. At same time, individual pretreatment variables may concur to determine a specific drug-response. Our narrative review focuses on these two key clinical aspects to summarize the state of art. Information from i) clinical trials and ii) the most relevant international guidelines is collected to assess the clinical and preclinical factors that may guide the use of lithium rather than valproate. Lithium may be effective in treating acute mania, and lithium efficacy is maximized when used to prevent both manic and depressive episodes. Lithium may be a better treatment choice in patients with: positive family history for bipolar disorder, mania-depression-interval pattern, few previous affective episodes/hospitalizations, high risk for suicide, no comorbidities. Valproate may be more effective as antimanic rather than prophylactic agent. Valproate might be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities. Finally, neither lithium nor valproate are suggested for the treatment of acute mixed states or bipolar depression. To consider clinical and preclinical factors may thus be useful to select the best treatment strategy.