Relevance of red blood cell Lithium concentration in the management of Lithium-treated bipolar and unipolar disorders: a systematic narrative review

Abstract

Abstract Background: Despite a variability in response and a narrow therapeutic index, lithium remains the gold standard treatment for bipolar disorders (BD), and a treatment of choice for non-bipolar mood disorders (MD). To date, the relevance of red blood cell (RBC) lithium monitoring remains unclear in the management of MD. This systematic review aims to provide a summary of areas in which the interest of lithium concentration monitoring was explored in the literature, and to discuss the relevance of such monitoring in the management of lithium-treated individuals. Methods: We conducted a systematic review, based on preferred reporting items for systematic reviews and Metanalysis (PRISMA) guidelines, of articles published between 1973 and February 2023, indexed in the following databases: EMBASE, MEDLINE, Cochrane Library. The search terms were combinations of the following headings: “Lithium AND Plasma AND Erythrocyte AND Mood disorders”. The systematic review protocol was published to PROSPERO (CRD42023406154). Results: Out of the 252 identified studies, 57 met the selection criteria. These studies primarily investigated the measurement of Red Blood Cell lithium concentration (RBCLC) in various areas: compliance (5 articles), SE/toxicity (13 articles), prediction of lithium response/therapeutic efficacy (17 articles), differences according to the type of MD (18 articles) and to the polarity of mood episodes (10 articles), associated clinical and socio-demographic factors (33 articles), and potential pathophysiological mechanisms (30 articles). The heterogeneity in methods and results, coupled with the limited amount of data, precludes any firm conclusion regarding the relevance of measuring RBCLC. However, the literature indicates a potential association between RBCLC and side effects (SE), particularly neurotoxicity. Surprisingly, the relevance of monitoring RBCLC is yet to be conclusively demonstrated, and its indications still require to be specified. In this context, we propose avenues of research aimed at exploring the relevance of measuring RBCLC. Conclusions: Despite decades of research on lithium, the relevance of monitoring RBCLC in the management of MD remains unclear. This underscores the imperative for high-quality research involving large representative samples.