Predictors of lithium response in bipolar disorder

While lithium is generally regarded as the first-line agent for patients with bipolar disorder, it does not work for everyone, which raises the question: can we predict who will be most likely to respond? In this paper, we review the most compelling clinical, biologic, and genetic predictors of lithium response in bipolar disorder. Among clinical factors, the strongest predictors of good response are fewer hospitalizations preceding treatment, an episodic course characterized by an illness pattern of mania followed by depression, and a later age at onset of bipolar disorder. While several biologic predictors have been studied, the results are preliminary and require replication with studies of larger patient samples over longer observation periods. Neuroimaging is a particularly promising method given that it might concurrently illuminate pathophysiologic underpinnings of bipolar disorder, the mechanism of action of lithium, and potential predictors of lithium response. The first genome-wide association study of lithium response was recently completed. No definitive results emerged, perhaps because the study was underpowered. With major new initiatives in progress aiming to identify genes and genetic variations associated with lithium response, there is much reason to be hopeful that clinically useful information might be generated within the next several years. This could ultimately translate into tests that could guide the choice of mood-stabilizing medication for patients. In addition, it might facilitate pharmacologic research aimed at developing newer, more effective medications that might act more quickly and yield fewer side effects.