Anti-bipolar therapy:
mechanism of action of lithium

by
Jope RS
Department of Psychiatry
and Behavioral Neurobiology,
University of Alabama at Birmingham,
35294-0017, USA.
jope@uab.edu
Mol Psychiatry 1999 Mar; 4(2):117-28


ABSTRACT

This review introduces the concepts that multiple actions of lithium are critical for its therapeutic effect, and that these complex effects stabilize neuronal activities, support neural plasticity, and provide neuroprotection. Three interacting systems appear most critical. (i) Modulation of neurotransmitters by lithium likely readjusts balances between excitatory and inhibitory activities, and decreased glutamatergic activity may contribute to neuroprotection. (ii) Lithium modulates signals impacting on the cytoskeleton, a dynamic system contributing to neural plasticity, at multiple levels, including glycogen synthase kinase-3beta, cyclic AMP-dependent kinase, and protein kinase C, which may be critical for the neural plasticity involved in mood recovery and stabilization. (iii) Lithium adjusts signaling activities regulating second messengers, transcription factors, and gene expression. The outcome of these effects appears likely to result in limiting the magnitudes of fluctuations in activities, contributing to a stabilizing influence induced by lithium, and neuroprotective effects may be derived from its modulation of gene expression.
Mania
5-HT1B
Lithium
Valproate
Gabapentin
Lamotrigine
Lithium at 50
Anticonvulsants
Beyond lithium?
Bipolar disorders
Drugs for bipolars
Lithium prophylaxis
Prozac and bipolars
Lithium augmentation
Lithium and depression
Lithium pharmacokinetics
Recurrent brief depression
Which antidepressants flick the switch?
Lithium for bipolars leads to fewer suicides
Lithium prophylaxis in unipolar major depressive disorder
Chronic lithium use, brain- and serum- DHEA and DHEA-sulphate


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