Sixty years of recurrence prevention in mood disorders. / Szescdziesiat lat profilaktyki nawrotów chorób afektywnych.

This year, we observe sixty's anniversary of the article by a British psychiatrist, Geoffrey Hartigan, demonstrating, for the first time, the possibility of preventing of the recurrence of mood disorders by using lithium salts. Herein, a history of prevention of recurrences of mood disorders both worldwide and in Poland will be presented concerning both lithium and other mood-stabilizing drugs. The merit for verifying the prophylactic lithium effect in the 1960-1970s should be given to Danish researchers, Mogens Schou and Poul Baastrup. In Poland, the first paper on prophylactic lithium appeared already in 1971. In the 1970s, French researchers showed prophylactic activity of valproic acid amide, and Japanese researchers - carbamazepine. In the 1980th, studies on valproic acid amide were performed in the 2nd Psychiatric Clinic of the Institute of Psychiatry and Neurology led by Prof. Puzynski. Since the mid-1990s, 2nd generation of mood-stabilizing drugs has been introduced, including some atypical antipsychotics (clozapine, olanzapine, quetiapine, aripiprazole, risperidone) and anticonvulsant drug, lamotrigine, showing prophylactic activity in bipolar mood disorder. The studies on lithium resulted in the identification of factors connected with its prophylactic efficacy as well as the antisuicidal, antiviral, and neuroprotective effects of this drug. From a sixty-year perspective following Hartigan's article, it seems that his pioneering concept on the possibility of pharmacological influence on the course of mood disorders was fully confirmed. Current Polish recommendations on pharmacological prophylaxis of mood disorders were presented in the books "Standardy leczenia niektórych zaburzen psychicznych" and "Psychofarmakologia kliniczna", both published in 2022.

Efficacy and Effectiveness of Lithium in the Long-Term Treatment of Bipolar Disorders: An Update 2018.

For more than 40 years, lithium has been the gold standard in the long-term treatment of bipolar disorders. In the course of the last 15 years, other drugs have been approved in this indication and are widely used in clinical practice at the expense of lithium. New research from the last few years, however, indicates that lithium is still the first-line treatment in this indication. Against this background and lithium's proven acute antimanic efficacy, we should perhaps be using lithium more regularly (in combination with an atypical antipsychotic, if necessary) right from the start for the acute treatment of a manic episode and, once remission has been achieved and euthymia maintained during continuation treatment, to regularly taper off the atypical antipsychotic, if possible, and continue with lithium as monotherapy for prophylactic treatment. This might lead to lithium being used more consistently with the scientific evidence in the long-term treatment of bipolar disorders. It remains uncertain, however, to predict who will respond to and tolerate lithium prophylactically, and more research is needed to deliver the best possible individualized care to our patients.

A Brief History of Lithium Treatment in Psychiatry.

The history of lithium as a psychiatric medication is marked by its serendipitous discovery, its lengthy path to US Food and Drug Administration approval, and controversy surrounding its current status in bipolar disorder treatment. Without doubt, the discovery of lithium as a psychotropic agent forever changed the course of psychiatry. The drug's fascinating, and sometimes contentious, history is reviewed here.

[Danish pioneers of psychopharmacology]. / Psykofarmakologiens danske pionerer.

Although a small country, Denmark has played an important role in the development of modern psychopharmacology due to an active and ambitious pharmacological industry, excellent researchers and last but not least, far-sighted clinicians. The most prominent among these clinicians are portrayed here. Mogens Schou advocated throughout his long life for the benefits of lithium treatment for bipolar patients, Lars Gram for the use of drug monitoring in the pharmacological treatment of depressed patients, Erik Jacobsen invented Antabus for treatment of alcohol dependence and later became one of the first presidents of the Collegium Internationale Neuropsychopharmacologicum (CINP) and finally, Claus Braestrup was the first to describe the benzodiazepine receptor.

The history of lithium therapy.

The use of lithium in psychiatry goes back to the mid-19th century. Early work, however, was soon forgotten, and John Cade is credited with reintroducing lithium to psychiatry for mania in 1949. Mogens Schou undertook a randomly controlled trial for mania in 1954, and in the course of that study became curious about lithium as a prophylactic for depressive illness. In 1970, the United States became the 50th country to admit lithium to the marketplace. Meanwhile, interest in lithium for the prophylaxis of depression was growing apace and today the agent is widely prescribed for that indication, even though it has not been accepted by the Food and Drug Administration. Lithium was almost derailed by a small group of opponents from the Maudsley Hospital and its status today is threatened by the "mood stabilizers."

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

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.

Lithium specificity in bipolar illness: a classic agent for the classic disorder.

For over half a century, lithium has been the gold standard amongst the pharmacological armamentarium used to treat bipolar disorder. Its ascendancy in this regard has been attributed partly to its primacy of discovery and clinical implementation; however, it is important to consider how it has achieved success and retained its prominence and whether this is because of its unique profile and specificity of actions. In this paper, we briefly discuss the clinical evidence in support of lithium specificity and argue for its continuing use in those patients most likely to benefit, namely, patients with 'classic' bipolar disorder. Further, we suggest that accurate characterization of 'lithium responders' through focused research is likely to yield novel treatments and assist in better understanding of the pathophysiology of the illness. In addition, the unique antisuicidal actions of lithium warrant further examination, as do its impressive properties as a prophylactic agent. This is particularly so given the high morbidity associated with bipolar disorder and its potential for suicide. Hence, in this paper, after describing the changing diagnostic backdrop against which much of the research to date has been conducted, we discuss the clinical therapeutic profile of lithium in both the acute and long-term management of bipolar disorder and its phenotypic specificity of action. We demonstrate that lithium possesses significant clinical and therapeutic efficacy that is very individual and thus remains the treatment of choice for bipolar disorder when used specifically in select patients.

[Lithium: 55 years of history in the therapy of bipolar affective disorder]. / Litio: 55 años de historia en el tratamiento del trastorno bipolar.

The clinical history of lithium began in mid-19th century when it was used to treat gout. It was subsequently administered as a substitute for sodium chloride and towards the end of 1940 its effects for the control of mania were discovered. At present it is used effectively for treatment of mania and for the prophylaxis of bipolar disorder. Though its effect on affective illnesses is evident, the same cannot be said of its mechanism of action, since in spite of the numerous studies performed to date it is still not known exactly how this ion acts. Many theories have been proposed, the most important of which are: normalisation of possible ionic alterations; interactions with the adenylyl cyclase cAMP system; effects on the phosphatidylinositol cycle; stabilisation of the levels of neuroprotective proteins; normalisation of the values of some cytosolic endopeptidases; etc. In any case, it has yet to be determined which of these is the principal factor responsible for lithium's therapeutic action, while at the same time the possibility cannot be totally ruled out that its precise mechanism of action is still to be discovered.

Litio: 55 años de historia en el tratamiento del trastorno bipolar / Lithium: 55 years of history in the therapy of bipolar affective disorder

La historia clínica del litio empezó a mediados del siglo xix, cuando se utilizó para el tratamiento de la gota. Posteriormente se administró como sustituto del cloruro sódico y a finales de 1940 se descubrieron sus efectos antimaníacos. En la actualidad se utiliza, de forma eficaz, para el tratamiento de la manía y para la profilaxis de la enfermedad bipolar. Si bien es evidente su efecto en las enfermedades afectivas, no sucede lo mismo con su mecanismo de acción, ya que, a pesar de los muchos estudios realizados, todavía no se conoce exactamente cómo actúa este ion. Se han propuesto muchas teorías, de las que destacan, como más importantes: normalización de posibles alteraciones iónicas, interacciones con el sistema adenilciclasa-AMPc efectos sobre el ciclo del fosfatidilinositol, estabilización de las concentraciones de proteínas neuroprotectoras y normalización de los valores de algunas endopeptidasas citosólicas, entre otros. De todas formas, todavía está por definir cuál de ellos es el principal responsable de las acciones terapéuticas del litio, aunque tampoco puede descartarse que aún esté por descubrir su mecanismo exacto de acción

The clinical history of lithium began in mid-19th century when it was used to treat gout. It was subsequently administered as a substitute for sodium chloride and towards the end of 1940 its effects for the control of mania were discovered. At present it is used effectively for treatment of mania and for the prophylaxis of bipolar disorder. Though its effect on affective illnesses is evident, the same cannot be said of its mechanism of action, since in spite of the numerous studies performed to date it is still not known exactly how this ion acts. Many theories have been proposed, the most important of which are: normalisation of possible ionic alterations; interactions with the adenylyl cyclase cAMP system; effects on the phosphatidylinositol cycle; stabilisation of the levels of neuroprotective proteins; normalisation of the values of some cytosolic endopeptidases; etc. In any case, it has yet to be determined which of these is the principal factor responsible for lithium's therapeutic action, while at the same time the possibility cannot be totally ruled out that its precise mechanism of action is still to be discovered