Predicting response to lithium in bipolar disorder: a critical review of pharmacogenetic studies

Background: It is difficult to reliably identify clinical predictors of lithium response. In recent years a number of pharmacogenetic studies have attempted to identify genetic variants which might be associated with response to lithium in bipolar patients. Aims: To critically review pharmacogenetic studies of lithium response in bipolar disorder and suggest strategies for future work in this field. Method: Computerized searches of electronic databases for studies published between 1966 and October 2007. Studies were selected for detailed review according to the following criteria: (i) contained original data; (ii) included bipolar patients (including DSM-IV BP-I and BP-II); and (iii) lithium was the prophylactic agent under study. Results: One hundred and fifty studies of interest were identified but only 15 relevant papers were selected for detailed review based on the selection criteria. Despite some interesting preliminary findings, there are substantial methodological limitations with almost all of the studies published to date. These issues are critically reviewed. Conclusions: The pharmacogenetics of lithium response in bipolar disorder remains a field in its infancy. There is a need for large-scale, prospective studies of biologically plausible candidate gene genes. The advent of genome-wide association studies holds particular promise for future studies