Lithium prophylaxis: A critical review

The prophylactic use of lithium had its origin in 1963 when Hartigan reported that maintenance doses of lithium carbonate were effective in preventing recurrence of manic and depressive episodes in patients with a history of frequent attacks. 1 This was followed by similar reports by Baastrup 2 and Baastrup and Schou. 3 The latter investigators reported that “lithium is the first drug demonstrated as a clear-cut prophylactic agent against one of the major psychoses.” 3 Prophylaxis in psychiatry is a unique concept, and it is not surprising that this claim aroused considerable interest and skepticism. Each of the aforementioned studies were longitudinal trials that compared frequency and severity of episodes during lithium therapy with frequency and severity during an equivalent period before lithium therapy. These studies were severely criticized on methodological grounds, 4–6 and lithium prophylaxis became a subject of international controversy. The critics contended that the issue of lithium prophylaxis could not be resolved by longitudinal trials and stressed the need for comparisons with placebo and control medication. Subsequently, there had been several comparisons of lithium with placebo and a few with imipramine. Because these studies are of key importance in the evaluation of lithium prophylaxis, they will be discussed individually.