Lamotrigine as a mood stabilizer: insights from the pre-clinical evidence

ABSTRACT

Introduction: Lamotrigine (LTG) is a well-established anticonvulsant that is also approved for the prevention of mood relapses in bipolar disorder. However, the mechanisms underlying LTG mood stabilizing effects remain unclear.

Areas covered: Herein, the pre-clinical evidence concerning LTG’s’ mode of action in depression and mania is reviewed. Bottlenecks and future perspectives for this expanding and promising field are also discussed. Pre-clinical studies have indicated that neurotransmitter systems, especially serotoninergic, noradrenergic and glutamatergic, as well as non-neurotransmitter pathways such as inflammation and oxidative processes might play a role in LTG’s antidepressant effects. The mechanisms underlying LTG’s anti-manic properties remain to be fully explored, but the available pre-clinical evidence points out to the role of glutamatergic neurotransmission, possibly through AMPA-receptors.

Expert opinion: A major limitation of current pre-clinical investigations is that there are no experimental models that recapitulate the complexity of bipolar disorder. Significant methodological differences concerning time and dose of LTG treatment, administration route, animal strains, and behavioral paradigms also hamper the reproducibility of the findings, leading to contradictory conclusions. Moreover, the role of other mechanisms (e.g. inositol phosphate and GSK3β pathways) implicated in the mode of action of different mood-stabilizers must also be consolidated with LTG.

KEYWORDS:

• Lamotrigine
• Bipolar Disorder
• Bipolar Depression
• Mania
• Serotonin
• Dopamine
• Glutamate
• BDNF
• Bcl-2
• Animal Models

Declaration of interest

AL Teixeira is a CNPq fellowship recipient while AS Miranda is a 2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have received financial support from the Brazilian government funding agencies: The National Council for Scientific and Technological Development (CNPq), Brazil and the Fundação de Amparo à Pesquisa de MG (FAPEMIG).