An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms

Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium's specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3 beta, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed. Furthermore, lithium has been proposed to exert its treatment effects through mechanisms associated with neuronal plasticity. In this review, we have overviewed the clinical aspects of lithium use for BD, and have focused on the neuroprotective and neurotrophic effects of lithium.