Mood Stabilizer Combinations: A Review of Safety and Efficacy

OBJECTIVE: Polypharmacy is common in the treatment of refractory bipolar disorder. The purpose of this article is to review the safety and efficacy of mood stabilizers in combinations. METHOD: A manual and computer (MEDLINE) search was performed for combinations of the most commonly used mood-stabilizing agents. RESULTS: The authors review safety and efficacy data on the more frequently encountered combinations of established and putative mood stabilizers. CONCLUSIONS: There have been few controlled studies of the use of combinations of mood stabilizers. The interactions of such combinations are sometimes complex, often very useful, and potentially dangerous. One general rule that may reduce the risks of toxic drug interactions is to add medication to the patient's current regimen in modest doses and increase the dose slowly. The safest and most efficacious mood stabilizer combinations appear to be the mixtures of anticonvulsants and lithium, particularly valproate plus lithium. Once the mechanisms of the mood stabilizers are identified, it is possible that a more rational approach to combination therapy will emerge, based on synergism at the sites of action.