Lithium's emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants.
BACKGROUND
The late onset of therapeutic response and a relatively large proportion of nonresponders to antidepressants remain major concerns in clinical practice. Therefore, there is a critical need for effective medication strategies that augment treatment with antidepressants.


METHODS
To review the available evidence on the use of lithium as an augmentation strategy to treat depressive episodes.


RESULTS
More than 30 open-label studies and 10 placebo-controlled double-blind trials have demonstrated substantial efficacy of lithium augmentation in the acute treatment of depressive episodes. Most of these studies were performed in unipolar depression and included all major classes of antidepressants, however mostly tricyclics. A meta-analysis including 10 randomized placebo-controlled trials has provided evidence that lithium augmentation has a statistically significant effect on the response rate compared to placebo with an odds ratio of 3.11, which corresponds to a number-needed-to-treat of 5. The meta-analysis revealed a mean response rate of 41.2% in the lithium group and 14.4% in the placebo group. One placebo-controlled trial in the continuation treatment phase showed that responders to acute-phase lithium augmentation should be maintained on the lithium-antidepressant combination for at least 12 months to prevent early relapses. Preliminary studies to assess genetic influences on response probability to lithium augmentation have suggested a predictive role of the -50T/C single nucleotide polymorphism of the GSK3beta gene.


CONCLUSIONS
Augmentation of antidepressants with lithium is currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants.
Bauer
Michael
M
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. michael.bauer@uniklinikum-dresden.de
Adli
Mazda
M
Bschor
Tom
T
Pilhatsch
Maximilian
M
Pfennig
Andrea
A
Sasse
Johanna
J
Schmid
Rita
R
Lewitzka
Ute
U
D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000928:Antidepressive Agents; D018692:Antimanic Agents; D018020:Lithium Compounds