From the Guidelines
Lithium primarily affects serotonin levels in the brain, enhancing its activity, which may contribute to its unique effects on reducing suicidal risk 1.
Key Points
- Lithium's mechanism of action is not fully understood, but its effects on serotonin are well-documented 1.
- The enhancement of serotonin activity by lithium may be responsible for its ability to reduce the recurrence of suicide attempts in adults with bipolar or other major affective disorders 1.
- While the exact neurotransmitters affected by lithium are not fully elucidated, serotonin is the most consistently implicated neurotransmitter in the literature 1.
- It is essential to note that lithium's effects on other neurotransmitters, such as dopamine and norepinephrine, are less clear and may require further research to fully understand its mechanism of action.
- In clinical practice, lithium is often used as a mood stabilizer in the treatment of bipolar disorder, and its effects on serotonin levels may contribute to its therapeutic efficacy 1.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Preclinical studies have shown that lithium alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown. The affected neurotransmitters are catecholamines. 2
From the Research
Neurotransmitters Affected by Lithium
The following neurotransmitters are affected by lithium:
- Dopamine: reduced excitatory neurotransmission 3
- Glutamate: reduced excitatory neurotransmission 3, slowed down synaptic vesicle cycling at glutamatergic synapses 4
- GABA: increased inhibitory neurotransmission 3
- Monoaminergic systems: alterations in various neurotransmitter systems, including monoaminergic systems 5
- Adrenergic system: interaction with the brain neurotransmitters, including the adrenergic system, particularly α2-adrenoceptor 6
Mechanisms of Action
Lithium's effects on neurotransmitters are thought to be mediated by its actions on:
- Signal transduction pathways, including guanine nucleotide-binding proteins, adenylyl cyclases, and protein kinase C isozymes 5
- Gene expression in the central nervous system, which may play a major role in the long-term stabilization of mood 5
- Second-messenger systems, such as the adenyl cyclase and phospho-inositide pathways, which may serve to dampen excessive excitatory neurotransmission 3
- Neuroprotective effects, including the reduction of oxidative stress and the increase of protective proteins such as brain-derived neurotrophic factor and B-cell lymphoma 2 3