Objective: This paper reviews controlled studies of bipolar depression, outlines criteria for choosing treatment, defines refractoriness in bipolar depression, and provides options for treatment of refractory bipolar depression.
Methods: Controlled studies that examined the efficacy of treatments for acute and long-term treatment of bipolar depression were located through electronic searches of several databases and by manual crosssearch of references and proceedings of international meetings.
Results: Lithium comes close to fulfilling the proposed criteria for first-line treatment for bipolar depression, and those not responding to lithium should be considered to have refractory bipolar depression. Options for such patients include addition of lamotrigine or a second mood stabilizer, or a newer-generation antidepressant such as a serotonin re-uptake inhibitor or bupropion, or the atypical antipsychotic olanzapine.
Conclusions: Although there is a paucity of research in the treatment of refractory bipolar depression, available data could be used for providing rational treatment options for such patients. However, further studies are urgently needed to determine which options are most appropriate for which type of patients.