A multidimensional analysis of adherence to lithium in type 1 bipolar disorder, in the R-Link cohort: a longitudinal study over 24 months

This prospective cohort study aims to analyse adherence to prophylactic lithium treatment in patients with type 1 bipolar disorder (BD1). It will be based on the European multicenter R-LiNK cohort. Approximately 60% of bipolar patients have poor adherence to prophylactic lithium treatment, the standard treatment for BD1, which is a major challenge to its effectiveness. Previous studies have highlighted different treatment adherence trajectories among bipolar patients. However, prospective studies investigating the determinants of adherence trajectories are lacking. To our knowledge, this is the first prospective study combining different tools to evaluate the determinants of adherence to lithium treatment across several assessments, in a naturalistic setting. The R-LiNK program collected multimodal data (clinical biomarkers, OMICs, imaging) before and three months after the initiation of lithium treatment, followed by a prospective follow-up of 24 months (monthly and quarterly assessments). Adherence was measured using the Tablet Routine Questionnaire (TRQ), a self-assessment tool that quantifies the number of doses missed over the past 7 and 30 days. Blood lithium levels provided an objective indicator of medication intake, although it may be influenced by various biological factors, such as pharmacokinetic profiles. TRQ scores have been shown to correlate with Lithium blood levels in previous studies. Determinants of adherence included participant characteristics, lifetime characteristics of the disorder (i.e. prevalence of depression or mania, number of hospitalizations), and evolution of the disorder after the initiation of treatment. The possible reasons for non-adherence were also assessed via subscales extracted from the Medication Adherence Rating Scale (MARS), a 10-item psychometric self-report questionnaire that explores therapeutic adherence behaviours, and the Beliefs about Medication Questionnaire (BMQ), which explores the impact of beliefs about treatment on therapeutic adherence. In this study, we will examine the concordance between different measures of adherence, to develop an overarching adherence measure. We will examine trajectories of adherence over a 24-month period and correlate them to clinical evolution. Finally, we will look for baseline predictors of adherence and analyse other reasons for non-adherence. The identification of risk profiles will allow for the adaptation of psychoeducational interventions and the optimization of the therapeutic response to lithium. Furthermore, the adherence study will define real-world exposure to Lithium, which might constitute a confounding factor in the final analysis of Lithium response in the R-Link study.