The Effectiveness of Lithium in the Treatment of Bipolar Disorder and Its Potential Health Risk

Lithium carbonate is one of the most prescribed mood stabilizers worldwide and remains the first-line pharmacological treatment for bipolar disorder (BD). Its therapeutic efficacy is well established; however, lithium (Li) has a narrow therapeutic index, and prolonged or excessive intake can cause renal, neurological, or endocrine toxicity. In Brazil and globally, lithium-based formulations are widely commercialized; however, only Brazil adopts a specific regulatory classification distinguishing reference, generic, and similar medicines. Despite its extensive clinical use, studies monitoring the actual Li concentration in pharmaceutical products are extremely scarce. This study quantified Li concentrations in different formulations available in Brazil to evaluate their chemical uniformity, estimated daily intake, and potential health risks. Samples were digested and analyzed using Inductively Coupled Plasma Optical Emission Spectrometry (ICP OES). Statistical analysis with the Kruskal–Wallis test revealed significant differences among formulations (p = 0.012), confirming non-uniform Li content. Measured concentrations ranged from 245.47 to 315.24 mg/kg, with generic products showing the highest values. The calculated daily intake (DI) and chronic daily intake (CDI) increased with therapeutic dose (600–1800 mg/day), and higher-dose regimens frequently exceeded the permitted daily exposure (PDE) value for Li established by International Council for Harmonisation Guideline for Elemental Impurities (Revision 2) (ICH Q3D (R2) (0.55 mg/day). Moreover, hazard quotient (HQ) values above 1 in some scenarios indicated potential health risks associated with excessive or long-term Li exposure. As one of the first studies to quantify Li in marketed formulations, this work underscores the need for systematic monitoring and stricter quality control to ensure therapeutic safety.