What is the optimal serum lithium level in the long-term treatment of bipolar disorder--a review?
OBJECTIVE
There is substantial uncertainty about the most efficacious serum lithium level for the long-term treatment of bipolar disorder (BD). 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' together with '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 BD 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 0.4 mmol/L with optimal response achieved at serum levels between 0.6-0.75 mmol/L. Lithium levels >0.75 mmol/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 0.2 mmol/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 0.6-0.75 mmol/L, while higher levels may benefit patients with predominantly manic symptoms.
Severus
W E
WE
Department of Psychiatry, University of Munich, Munich, Germany. emanuel.severus@med.uni-muenchen.de
Kleindienst
N
N
Seemüller
F
F
Frangou
S
S
Möller
H J
HJ
Greil
W
W
D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D016651:Lithium Carbonate / Q000097:blood* / Q000627:therapeutic use*; D012008:Recurrence; D012016:Reference Values; D012307:Risk Factors; D013997:Time Factors
D014150:Antipsychotic Agents; D016651:Lithium Carbonate