ABSTRACT
I will examine the evidence that prophylactic lithium is effective in unipolar depression. Presented elsewhere in this volume is the discussion of the use of lithium for the treatment of acute depression. My view is that there are a small number of controlled studies showing that lithium may have some efficacy in acute depression and has clear efficacy as augmentation for acute depression. I review here the large body of information on maintenance lithium for prophylaxis in unipolar depression, based on both double-blind, random-assignment studies and case-controlled studies, generally carried out in the 1950s, 1960s and 1970s. Although antidepressants are now considered the standard treatment for preventing the recurrence of depression and are recommended by various guidelines, there may still be a role for lithium in selected cases. Depressed patients currently would have received antidepressants for their acute episode, so continued treatment with a drug that is effective for the acute episode would be the first choice for maintenance treatment. There are more data on the preventive
properties of lithium for unipolar depression than there are for the prophylactic properties of many of the anticonvulsants used for bipolar illness. I have identified the controlled studies of maintenance lithium for unipolar depression and present in this chapter a new meta-analysis of the efficacy of lithium for unipolar depression. I compare the prophylactic efficacy of lithium in unipolar disease to that of lithium in bipolar disease, as an active comparator. The efficacy of lithium for this purpose has been questioned by many authors (for example in references 1 and 2, the possibility that withdrawal of lithium induces abrupt relapse). We move beyond rhetoric to examine what the data show about the efficacy of lithium from approximately 400 unipolar patients and 2000 bipolar patients, for comparison, in controlled clinical trials, with an emphasis on methodological rigor.
