Lithium Clinics in Berlin and Dresden: a 50-Year Experience.

Although lithium's serendipitous discovery as a medication for depression dates back more than 200 years, the first scientific evidence that it prevents mania and depression arose only in the 1960s. However, at that time there was a lack of knowledge about how to administer and monitor lithium therapy safely and properly. The lithium clinics in Dresden and Berlin were remarkably similar in their beginnings in the late 1960s regarding patient numbers and scientific expertise without being aware of one another due to the Iron Curtain separating Germany into a western and eastern part until 1990. In what were initially lithium-care programs run independently from one another, the lithium clinics embedded in academic settings in Dresden and Berlin represent a milestone in the history of psychopharmacological treatment of affective disorders in Germany and trailblazers for today's lithium therapy. Nowadays, lithium's clinical applications are unquestioned, such as its use in strategies to prevent mood episodes and suicide, and to treat depression. The extensively documented knowledge of lithium treatment is the fruit of more than 50 years of observing disease courses and of studying side effects and influencing factors of lithium prophylaxis. Its safe and proper administration-in determining the correct indication, baseline and follow-up examinations, recommended dosages, monitoring, or the management of side effects-is well established. Subsequently, both national and international guidelines continue recommending lithium as the gold standard in treating patients with unipolar and bipolar disorders.

Lithium: bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium.

Bipolar illness is a major psychiatric disorder that affects 1-3% of the worldwide population. Epidemiological studies have demonstrated that this illness is substantially heritable. However, the genetic characteristics remain unknown and a clear personality has not been identified for these patients. The clinical history of lithium began in mid-19th century when it was used to treat gout. In 1940, it was used as a substitute for sodium chloride in hypertensive patients. However, it was then banned, as it had major side effects. In 1949, Cade reported that lithium could be used as an effective treatment for bipolar disorder and subsequent studies confirmed this effect. Over the years, different authors have proposed many biochemical and biological effects of lithium in the brain. In this review, the main mechanisms of lithium action are summarised, including ion dysregulation; effects on neurotransmitter signalling; the interaction of lithium with the adenylyl cyclase system; inositol phosphate and protein kinase C signalling; and possible effects on arachidonic acid metabolism. However, none of the above mechanisms are definitive, and sometimes results have been contradictory. Recent advances in cellular and molecular biology have reported that lithium may represent an effective therapeutic strategy for treating neurodegenerative disorders like Alzheimer's disease, due to its effects on neuroprotective proteins like Bcl-2 and its actions on regulators of apoptosis and cellular resilience, such as GSK-3. However, results are contradictory and more specific studies into the use of lithium in therapeutic approaches for neurodegenerative diseases are required.

The role of serendipity in drug discovery.

Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. It has also played a role in the discovery of several drugs that have had an impact on the development of psychiatry. "Serendipity" in drug discovery implies the finding of one thing while looking for something else. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, i.e., aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. In the case of three drugs, i.e., potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, i.e., iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck.