Lithium as a disease-modifying drug for bipolar disorder

Lithium is a classic, primary treatment for bipolar disorder that has paradoxically been used less over time, especially in North America, which goes against the accumulating evidence for its efficacy. Bipolar disorder is increasingly conceptualised as a chronic, potentially progressive condition worsened and accelerated by each mood episode, which might resemble multiple sclerosis or rheumatoid arthritis as a condition that requires disease-modifying treatments to change illness trajectory. In this Personal View, we argue that lithium acts like a disease-modifying drug in bipolar disorder. Although the pathophysiology of bipolar disorder remains unclear, many of the mechanisms implicated in bipolar disorder, and the surrogate markers associated with this condition, are uniquely affected by lithium treatment from the DNA and cellular levels to the structure and function of the brain and other body systems. Clinical trial and cohort study evidence shows that lithium is effective and probably superior to other medications used to treat bipolar disorder, and that long-term outcomes are better with lithium than non-lithium regimens. Conceptualisation of lithium as a disease-modifying agent might help to increase clinical use by doctors, especially early in the disease course to better serve our patients.