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 treatment is necessary to prevent recurrence and reduce the loss of productivity and increased medical costs associated with this illness. The agent with the most evidence of efficacy and the only U.S. Food and Drug 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 disorder and reduce suicide risk by more than 8-fold. However, lithium may be more effective for patients with classical features such as fully remitting courses and typical manic symptoms than for patients with nonclassical bipolar features such as mixed states and rapid cycling. Because lithium may be toxic at only twice the therapeutic dose, physicians should consider patients' ages and medical history when prescribing this drug. Monitoring requirements; possible side effects; changes in the illness including more treatment-resistant forms; and the introduction of newer agents, which are supported by more marketing and continuing medical education programs than the essentially generic drug lithium, have contributed 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 the dose 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-line long-term treatment for bipolar disorder, either as monotherapy or in combination therapy.