Evidence based combination therapy for bipolar disorder

Abstract

The treatment of bipolar illness is complex and full of caveats for the clinician, and it seems that at least some aspects of the disorder are rather refractory to treatment. While some agents are efficacious as monotherapy, the overall outcome is unsatisfactory. However, only specific combinations have solid evidence supporting their efficacy. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/or rapid cycling when utilized as monotherapy however only fluoxetine in combination with olanzapine has data supporting its usefulness for the treatment of bipolar depression. Adding an antipsychotic to acutely manic patients who are partial responders to lithium/valproate/carbamazepine is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients refractory to monotherapy could benefit with add on treatment with olanzapine, valproate, an antidepressant or lamotrigine, depending on the index acute phase. Combination therapy may improve treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.