Socio-demographic and clinical predictors of outcome to long-term treatment with lithium in bipolar disorders: a systematic review of the contemporary literature and recommendations from the ISBD/IGSLI Task Force on treatment with lithium

Abstract

Objective To identify possible socio-demographic and clinical factors associated with Good Outcome (GO) as compared with Poor Outcome (PO) in adult patients diagnosed with Bipolar Disorder (BD) who received long-term treatment with lithium. Methods A comprehensive search of major electronic databases was performed to identify relevant studies that included adults patients (18 years or older) with a diagnosis of BD and reported sociodemographic and/or clinical variables associated with treatment response and/or with illness outcome during long-term treatment to lithium (> = 6 months). The quality of the studies was scored using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institute of Health. Results Following review, 34 publications (from 31 independent datasets) were eligible for inclusion in this review. Most of them (n = 25) used a retrospective design. Only 11 studies were graded as good or borderline good quality. Forty-three potential predictors of outcome to lithium were identified. Four factors were associated with PO to lithium: alcohol use disorder; personality disorders; higher lifetime number of hospital admissions and rapid cycling pattern. Two factors were associated with GO in patients treated with lithium: good social support and episodic evolution of BD. However, when the synthesis of findings was limited to the highest (good or borderline good) quality studies (11 studies), only higher lifetime number of hospitalization admissions remained associated with PO to lithium and no associations remained for GO to lithium. Conclusion Despite decades of research on lithium and its clinical use, besides lifetime number of hospital admissions, no factor being consistently associated with GO or PO to lithium was identified. Hence, there remains a substantial gap in our understanding of predictors of outcome of lithium treatment indicating there is a need of high quality research on large representative samples.

An ecological study of objective rest–activity markers of lithium response in bipolar-I-disorder

“…Furthermore, in clinical practice, Li response can be viewed as a dimensional rather than a categorical construct (Scott, Etain, Nierenberg & Bellivier, 2020). In this study, we chose to classify individuals into GR or NR groups as this was the most reported measure of Li response in a recent systematic review (Grillaut-Laroche, Etain, Severus, Scott, & Bellivier, 2020). However, other prospective assessments of Li response and those that measure continuous or categorical outcomes should be considered instead of or as well the Alda scale.…”

Lithium and Valproate in Bipolar Disorder: From International Evidence-based Guidelines to Clinical Predictors

“…In 3 prospective studies (n = 101; n = 336; n = 442) rapid cycling course is predictive of poor response to lithium [ 59 - 61 ], but not to valproate in one of these [ 59 ]. History of rapid cycling is associated with poor outcome to lithium in 2 meta-analyses and in a review of respectively 20 (n = 2,054), 71 (n = 17,396), 34 (n = 12,602) studies [ 62 - 64 ]. Body of evidence is considered too inconsistent in a systematic review of 43 (n = 4,280) studies [ 65 ].…”

“…In a post hoc RCT (n = 165) analysis of the relationship between treatment response and the number of previous affective episodes find that > 3 depressive and > 11 maniac episodes are associated with poor lithium response but not to valproate response [ 68 ]. History of previous hospitalizations is considered predictive to poor outcome to lithium in a meta-analysis and in 2 systematic reviews [ 63 - 65 ], in prospective (n = 402) and RCT (n = 372) studies [ 61 , 69 ], related to an inferior outcome than valproate in one of these studies [ 69 ].…”

Pharmacogenomics of Lithium Response in Bipolar Disorder

“… Genetic, Biological, and Clinical Predictors of Lithium Response in Bipolar Disorder [ 5 , 8 , 9 , 10 , 11 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 40 , 44 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. …”

“…Pharmacogenetic studies are attempting to identify response or tolerability biomarkers, but the process of cherry-picking candidate genes has been proven not to be ideal considering the size of the human genome [ 2 ]. Favorable response is more likely for patients with a BD-I diagnosis, few comorbidities, manic/hypomanic-depression-euthymic interval cycle pattern, early age of symptom onset and treatment onset, family history of BD, and adequate drug adherence [ 8 , 9 , 10 ]. Familial clusters may be a prognosticator for recurrent mood episodes due to patients with good lithium response tending to cluster in families, but alone this datum holds little weight [ 11 ].…”