Monotherapy Versus Combined Treatment With Second-Generation Antipsychotics in Bipolar Disorder

The American Psychiatric Association guidelines for treating bipolar disorder recommend combination therapies to treat patients experiencing severe acute manic or mixed episodes and breakthrough manic or mixed episodes during maintenance therapy. Combination therapies approved by the U.S. Food and Drug Administration for the treatment of acute manic states include the use of second-generation antipsychotics, such as olanzapine, risperidone, quetiapine, and aripiprazole in combination with lithium or divalproex; for the treatment of acute bipolar depression, the olanzapine plus fluoxetine combination; and for maintenance treatment, quetiapine combined with lithium or valproate. When combining medications for the management of patients with bipolar disorders, physicians face a potentially complex treatment strategy. Available agents have different mechanisms of action, routes of metabolism and excretion, therapeutic effects, and side effects. Combining treatments can be advantageous owing to therapeutic synergy; however, the liability is an increased possibility of adverse effects. The decision to use a combination therapy should be made on the basis of the efficacy, tolerability, and safety of each medication and their specific combination for individual patients.