Mechanism of Action of Lithium – A Synopsis and Visual Guide

Posted on February 9, 2019
Time to read: 8 minutes

Lithium is a unique agent that has been used for over half a century for the treatment of bipolar affective disorder.  Lithium has compelling evidence in the treatment of mania, acute bipolar depression and prophylaxis in bipolar affective disorder. [1]

It is also one of the two agents that have anti-suicidal properties in psychiatry, the other being clozapine. [2] Despite the significant evidence which is in favour of lithium for both prophylaxis bipolar affective disorder and as an anti-suicidal agent, its use is declining since the beginning of the 21st century.

It thus becomes crucial for clinicians to consider lithium as an important part of the management of bipolar affective disorder.  Despite its first discovery 1949 and its subsequent use, the exact mechanisms of action in lithium are unclear.

In this article, we summarise lithium’s multitude of mechanisms of action.

We have previously covered lithium’s mechanism of action with a focus on neuroprotection along with another article on lithium with prescribing and monitoring in clinical practice.

In this article, we focus on two key aspects

  1.  Lithium’s action on neurotransmitters and second messenger systems
  2. Intracellular mechanisms of action which converge towards neuroprotection.

The main reference for this article is : Potential Mechanisms of Action of Lithium in Bipolar Disorder by Malhi et al., 2013. [3]


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