70 Years of Research and 50 Years of Lithium Clinics: From Serendipity to Gold Standard in Mood Disorders

This special issue of Pharmacopsychiatry is dedicated to a “miracle drug” that can nowadays be considered the psychotropic medication with the longest clinical application in modern psychiatry: lithium. On the occasion of celebrating the 50th birthday of lithium clinics in Dresden and Berlin, historical aspects, clinical evidence and applications, and the latest molecular and genetics findings from contemporary lithium research were reviewed at the 31st Annual Meeting of the International Group for the Study of Lithium-Treated Patients (IGSLI), held in Dresden, Germany, November 9–12, 2017. The issue of this journal contains 8 comprehensive review papers predominantly written by researchers from the IGSLI group, a network of researchers that has worked in, and significantly contributed to, the core areas of lithium research since its foundation in 1988 (www.igsli.org). The articles are supplemented with 3 related invited commentaries by international experts shedding light on global perspectives and controversies of its use.

Some people call lithium the “aspirin of psychiatry” because, like the classic painkiller of the 20th century, many different clinical effects in humans have been discovered during the past decades. Since its introduction in modern psychiatry in 1949, from the breakthrough of identifying lithium salts as having antimanic and prophylactic activity, many new aspects of its use in psychiatry have been discovered in basic and clinical research, including antisuicidal, antidepressant, and neuroprotective properties. The latest research suggests that lithium may even hold potential in preventing and treating dementia and other neurodegenerative diseases.

Today, lithium is an essential medication for patients with mood disorders and represents the most valuable treatment option in the long-term treatment of bipolar disorders. When used correctly, lithium unquestionably produces the most dramatic benefits of any medication in psychopharmacology. Two meta-analyses of placebo-controlled trials (RCTs) confirmed its efficacy regarding the prevention of overall mood episodes, manic episodes, depressive episodes (dependent on the type of analyses performed), and acceptability. Recent results from population-based cohort studies and a systematic review of the evidence from observational studies also found lithium to be superior to other mood stabilizers in the long-term treatment of bipolar disorders [1].

Despite the fact that lithium has unique properties as an effective mood stabilizer and demonstrates antisuicidal and antidepressant effects, lithium is dramatically underutilized in many countries, the United States in particular. This is not the case in many European countries, Australia, New Zealand, China, and India, as Gin Malhi points out in his commentary. Although lithium is ranked consistently as a first-choice medication for the long-term treatment of bipolar disorders in all major international treatment guidelines, the question is, why is it underprescribed in some countries? Michael Gitlin states in his commentary, “Lithium: An American Perspective,” that despite the considerable efficacy and advantages achieved by lithium, it remains a medication that, compared with most psychotropic medications, is slightly more difficult to handle, largely due to its narrow therapeutic index. This factor, along with concerns about its tolerability and long-term renal risks, probably explains why lithium is underutilized. There is also the perception that the frequent and reliable monitoring of lithium plasma concentrations is difficult. Many experts, however, consider lithium, when used properly (and reliable lithium plasma concentrations are monitored), that it is relatively well tolerated and easy to administer. Among these factors, one other reason for its underutilization is that lithium is inherently a generic drug with no major pharmaceutical firm sponsor that would finance its global marketing. In contrast, many other treatments have each enjoyed a substantial period of patent protection, leading to intense marketing of the medication to psychiatrists and patients alike.

Nevertheless, beyond controversy, lithium has provided dramatic improvements in the course of patients’ illnesses, saved many lives, and remains the mainstay for the treatment of people suffering severe mood disorders. Happy 50th anniversary, lithium clinics.

• Reference

• 1 Severus E, Bauer M, Geddes J. Efficacy and effectiveness of lithium in the long-term treatment of bipolar disorders: An update 2018. Pharmacopsychiatry 2018; 51: 173–176