Cross-validation of clinical characteristics and treatment patterns associated with phenotypes for lithium response defined by the Alda scale

- This study examines simultaneously different methods of rating lithium response using the most widely used scale (the Alda Scale).
- Using continuous scores of lithium response or response categories leads to different predictors of response or non-response being identified.
- High B scale scores are associated with clinical features that are common in clinical populations such as the presence of alcohol or substance misuse or psychotic symptoms.
- This cross validation approach offers a useful methodology for exploring the utility of the Alda scale and other reliable measures of lithium response.
- A limitation of the findings is that rating scale is that it is primarily a retrospective measure of response.

BackgroundIt is increasingly recognised that reliable and valid assessments of lithium response are needed in order to target more efficiently the use of this medication in bipolar disorders (BD) and to identify genotypes, endophenotypes and biomarkers of response.MethodsIn a large, multi-centre, clinically representative sample of 300 cases of BD, we assess external clinical validators of lithium response phenotypes as defined using three different recommended approaches to scoring the Alda lithium response scale. The scale comprises an A scale (rating lithium response) and a B scale (assessing confounders).ResultsAnalysis of the two continuous scoring methods (A scale score minus the B scale score, or A scale score in those with a low B scale score) demonstrated that 21-23% of the explained variance in lithium response was accounted for by a positive family history of BD I and the early introduction of lithium. Categorical definitions of response suggest poor response is also associated with a positive history of alcohol and/or substance use comorbidities. High B scale scores were significantly associated with longer duration of illness prior to receiving lithium and the presence of psychotic symptoms.LimitationsThe original sample was not recruited specifically to study lithium response. The Alda scale is designed to assess response retrospectively.ConclusionsThis cross-validation study identifies different clinical phenotypes of lithium response when defined by continuous or categorical measures. Future clinical, genetic and biomarker studies should report both the findings and the method employed to assess lithium response according to the Alda scale.