The lithium ion: a foundation for psychopharmacological specificity

The idea of lithium's specificity for bipolar disorder was proposed in Cade's original work in 1949. Since then, many controlled studies have been performed, examining lithium for treatment of bipolar disorder and other psychiatric conditions. This review was undertaken to determine if the suggestion of lithium's specificity has support in the controlled studies conducted after Cade's initial proposal. Studies were selected in a Medline search, dating back to 1966 and also identified from the bibliography of some of these papers. The controlled trials with lithium for the treatment of mania and bipolar depression, unipolar depression, schizophrenia, and schizoaffective disorder were reviewed. The published studies with lithium in other neuropsychiatric conditions were also considered. Additionally, we reviewed literature on other therapeutic agents proposed for bipolar disorder, looking at their comparative effectiveness to lithium. The data analyzed give strong support for lithium's being most effective in bipolar disorder, with minimal or no therapeutic effects in other neuropsychiatric disorders. The neurochemical underpinnings of this specificity are being investigated, without conclusive findings to date. The study of this paradigm of specificity in neuropsychopharmacology research may lead to meaningful contributions to understanding the pathophysiology of bipolar disorder and may help to develop newer treatments for this condition.