Background: Although depression accounts for a large part of the burden associated with bipolar disorder, its drug treatment has been under-studied.
Objective: To provide the best available evidence supporting the pharmacotherapy of bipolar depression.
Methods: A systematic review was conducted, focusing on randomized, controlled trials (RCTs) and meta-analyses.
Results/conclusions: Despite FDA approval of both the olanzapine-fluoxetine combination and quetiapine for the treatment of acute bipolar depression, independent RCTs (i.e., not trials conducted 'under the umbrella' of a drug company) have not found any drug to have antidepressant effects similar to those seen in unipolar depression. A practice-based suggestion, valuable for both short- and long-term treatment, might be to have a background of mood stabilizers and to add drugs, following one of several treatment options, trusting to find a drug with a degree of effectiveness by trial and error. The list of drugs that could be used would include all the current antidepressants, the olanzapine-fluoxetine combination and probably quetiapine too. Special features and situations might also influence treatment options.