Bipolar: Mood Stabilizer Prescribing

Mood stabilizers are the cornerstone of bipolar disorder pharmacotherapy, targeting distinct neurobiological mechanisms to prevent manic and depressive recurrences. Lithium, the prototypical mood stabilizer, is a monovalent cation that competes with sodium at ion channels and modulates intracellular signaling. Its primary mechanisms include inhibition of inositol monophosphatase (depleting the phosphatidylinositol second messenger system, thereby reducing neuronal excitability), inhibition of glycogen synthase kinase-3 beta (GSK-3β, which regulates gene transcription, neuroplasticity, and circadian rhythms), and enhancement of serotonergic neurotransmission. Lithium uniquely increases brain-derived neurotrophic factor (BDNF) and promotes neuroprotective gray matter volume preservation. Valproate (valproic acid/divalproex) acts through multiple mechanisms: it enhances GABAergic inhibition by inhibiting GABA transaminase (increasing GABA availability) and blocking voltage-gated sodium channels (reducing neuronal firing), and it modulates histone deacetylase (HDAC) activity affecting gene expression. Valproate is hepatically metabolized via glucuronidation and beta-oxidation, with dose-dependent protein binding (90% at low levels, decreasing at higher concentrations, leading to unpredictable free drug levels). Lamotrigine stabilizes neuronal membranes by blocking voltage-sensitive sodium channels and inhibiting glutamate release, its primary mechanism for preventing excitotoxicity. Unlike lithium and valproate, lamotrigine is primarily effective...