Prophylactic treatment of bipolar disorders with lithium, carbamazepine and valproic acid:: evidences and controversies

To arrive at a rational decision in the selection of an appropriate mood stabilizer in bipolar disorder, the scientific findings, as determined through evidence-based medicine, of studies on prophylactic treatment of bipolar disorder with lithium, carbamazepine and valproate should be considered. Lithium is the treatment of first choice particularly in patients with a typical and classical course of bipolar disorder who show no comorbidity, but mood-congruent symptoms and complete remission between the episodes. Furthermore, lithium has specific antisuicidal and antiaggressive effects and reduces the high excess mortality of patients with bipolar disorder to that of the normal population. Carbamazepine is the drug of second choice for the prophylactic treatment of bipolar disorder Carbamazepine is supposed to be superior to lithium in patients with mood-incongruent symptoms and psychiatric comorbidity. Valproate is currently not marketed for the treatment of bipolar disorder in Europe. Thus, valproate, showing possibly a similar spectrum of activity as carbamazepine, is currently only available as an experimental mood stabilizer its use has been suggested particularly for patients with rapid cycling bipolar disorder. Compared to carbamazepine, valproate would have advantages with respect to a lower risk of severe negative pharmacological interactions. For both carbamazepine and valproate, a specific antisuicidal effect has not been demonstrated. Therefore, lithium should always be considered the mood stabilizer of choice for the prophylactic treatment of bipolar disorder in patients with a history of suicidality. Strategies to optimize prophylactic treatment in case of partial ol non-response should consider the criteria "suicccde risk" and "atypical features". A specific algorithm in order to help doctors in,making rational therapeutic decisions is presented.