Rationale for Long-Term Treatment of Bipolar Disorder and Evidence for Long-Term Lithium Treatment

Because of the great morbidity and mortality associated with bipolar disorder, long-term treatmentis necessary to prevent recurrence and reduce the loss of productivity and increased medical costs associatedwith this illness. The agent with the most evidence of efficacy and the only U.S. Food andDrug Administration-approved medication for maintenance treatment of bipolar disorder is lithium.Lithium may cause a prophylactic response in more than two thirds of patients with bipolar disorderand reduce suicide risk by more than 8-fold. However, lithium may be more effective for patients withclassical features such as fully remitting courses and typical manic symptoms than for patients withnonclassical bipolar features such as mixed states and rapid cycling. Because lithium may be toxic atonly twice the therapeutic dose, physicians should consider patients’ ages and medical history whenprescribing this drug. Monitoring requirements; possible side effects; changes in the illness includingmore treatment-resistant forms; and the introduction of newer agents, which are supported by moremarketing and continuing medical education programs than the essentially generic drug lithium, havecontributed to the decline in lithium prescription rates in the last 15 years in the United States. However,long-term treatment with lithium continues to be effective in many patients, especially if thedose is periodically evaluated as patients experience changes in their physical health and lithium tolerance.Until newer agents have comparable evidence of efficacy, lithium will be considered a first-linelong-term treatment for bipolar disorder, either as monotherapy or in combination therapy.