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Abstract
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.