Lithium Formulations in Clinical Practice

Lithium has remained one of the most established treatments for mood disorders for more than seven decades. Evidence supports its effectiveness in the management of acute manic episodes and in the prevention of relapse in bipolar disorder during maintenance therapy. In addition to its mood-stabilizing properties, lithium is distinguished by a clinically relevant anti-suicidal effect, supported by current evidence showing reduced rates of suicidal behavior in patients with recurrent mood disorders. Different salts, including carbonate and sulfate, are available as Immediate-Release (IR) and Sustained-Release (SR) formulations. SR formulations are associated with slower absorption and delayed peak concentrations, smaller peak-trough fluctuations, and fewer peak-related adverse effects, while achieving a comparable overall exposure to IR formulations. Among SR options, lithium sulfate deserves specific consideration because formulation-dependent properties may favor more predictable absorption and a steadier serum concentration profile. This review summarizes current evidence regarding lithium use across the lifespan, with particular focus on the pharmacokinetic characteristics and clinical implications of different lithium formulations. We discuss practical aspects relevant to routine care, including laboratory and therapeutic drug monitoring, clinically relevant food and drug interactions, toxicity management, switching strategies, and treatment considerations in vulnerable populations, including those with impaired renal function, older adults, children and adolescents, and women during pregnancy and the postpartum period. Overall, SR formulations may offer practical advantages in individualized long-term treatment by improving tolerability and facilitating once-daily administration, although the currently available evidence remains limited by the lack of large direct comparative trials and the predominance of observational studies.