After Cade’s [1] observation had been confirmed by four placebocontrolled
cross-over studies conducted between 1954 and 1971
as reviewed by Goodwin and Jamison [4], the antimanic efficacy
of lithium was evaluated in several comparative RCTs conducted
from 1970 to 1980, using chlorpromazine or haloperidol as the
reference drug. Most of these studies found lithium to be as least
as effective as the comparator; however, sample sizes were generally
small [2,12]. In the largest and only conclusive of these
studies, chlorpromazine was superior to lithium in the highly active
patients whereas in the mildly active, lithium and chlorpromazine
were comparable [13]. From 1980 and onwards, other putative
antimanic agents were compared to lithium in a number of
small, investigator-sponsored, essentially inconclusive trials, albeit
all supporting antimanic potentials of lithium [2,12].