Objectives: There is substantial uncertainty about the most efficacious serum lithium level for the long-term treatment of bipolar disorder. This review focuses on the available evidence taking into consideration the effects of previous lithium history, changes in lithium level and polarity of relapse or recurrence. Methods: We conducted a Medline search, using the MeSH Terms “bipolar disorder“ AND “lithium“ AND (“Randomized Controlled Trial“ OR “Controlled Clinical Trial“) covering the time span from 1966 to March 2006. We only included studies reporting on the long-term treatment of mood disorders where patients with bipolar disorder were examined as a separate group and were assigned to precisely specified target ranges of lithium level. Results: The minimum efficacious serum lithium level in the long-term treatment of bipolar disorder was 0.4mmol/l with optimal response achieved at serum levels between 0.6–0.75mmol/l. Lithium levels >0.75mmol/l may not confer additional protection against overall morbidity but may further improve control of inter-episode manic symptoms. Abrupt reduction of serum levels of more than 0.2mmol/l was associated with increased risk of relapse. Conclusions: In the long-term treatment of bipolar disorder clinicians should initially aim for serum lithium levels of 0.6–0.75mmol/l while higher levels may benefit patients with predominantly manic symptoms.
