Variabilité de la réponse au lithium

Abstract

Bipolar disorder (2% of the general population) is a major affective disorder associated with considerable burden and costs. Lithium (Li) is the leading treatment for relapse prevention in bipolar disorders with many patients who remain asymptomatic for several years (even decades). In addition, it is the only psychoactive drug that has demonstrated efficacy in suicide prevention. However a large proportion of patients is experiencing very high relapse rates (overall between 70 and 80% relapse, two years after a major episode). The management of Li treatment is complicated by several uncertainties: (i) the pharmacodynamic and therapeutic mechanism of action of lithium (Li) remains widely unknown, (ii) no recent pharmacokinetic studies using modern modeling approaches is available, (iii) finally, data are dramatically lacking for the extended release form of lithium that is used nowadays in a large majority of patients. Transport mechanisms of Li transport through the blood-brain barrier (BBB) remain unknown and very little is also known on the effect of Li chronic exposure on the expression of some BBB biomarkers especially those involved in transport and metabolism of drugs. The BBB is likely to play an important role in lithium efficacy. Very little is known about the correlation between brain and blood lithium levels and mechanisms involved in the lithium transport at the BBB remain largely unexplored. PK parameters and PK-PD relationships of plasma and intra-erythrocyte lithium levels (using lithium extended release) of lithium extended release are also lacking. In this article, we review the potential developments of research on lithium response variability.