A critical appraisal of lithium’s efficacy and effectiveness: the last 60 years


  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Corresponding author:
Paul Grof, M.D., Ph.D. Mood Disorders Centre of Ottawa Smyth Medical Centre 202-1929 Russell Road Ottawa, ON, Canada, K1G 4G3 Fax: 613 526 3092 e-mail: paul_grof@mdco.ca


The history that depicts the evaluation of lithium’s efficacy presents an interesting contrast: on the one hand, conviction that, of all psychotropic drugs, lithium has the best demonstrated efficacy; on the other hand, repeated attempts to question it. Those contesting lithium’s stabilizing abilities have argued from several angles, for example that the proof was methodologically incorrect or insufficient, that the number of responders is small, or that the response is poor in practice and does not last. But there is a good explanation for this paradox. While the early challenges to lithium’s value in recurrent mood disorders reflected mainly that psychiatry had not yet developed a methodology suitable for testing long-term efficacy, more recent questioning has resulted mostly from retesting its efficacy and effectiveness in a substantially broadened bipolar spectrum, outside the classical diagnosis. Lithium, however, continues to stabilize very well the patients suffering from typical bipolar disorder—the condition for which its efficacy was originally demonstrated. More recently, lithium has also proven to dramatically reduce suicidal behavior and mortality and to augment markedly the efficacy of antidepressants in unresponsive patients.