A half-century of participant observation in psychiatry. Part III: psychopharmacology. / Pól wieku obserwacji uczestniczacej w psychiatrii. Czesc III. Psychofarmakologia.

The third part of the triptych of my 50-year activity in psychiatry is about psychopharmacology. This way of treatment changed the picture of contemporary psychiatry. The introduction of neuroleptic (antipsychotic) drugs and tricyclic antidepressants in the 1950s resulted in a therapeutic revolution and contributed to the ?medicalization' of psychiatry and its therapeutic similarity to other non-surgical specialties. Adiscovery of prophylactic lithium activity in the1960s initiated the mood-stabilizing drugs.During the last half-century, the most dynamic was the 1990s when most antipsychotic and antidepressant drugs of the so-called new generation were introduced. The twenty-first century marks a debut of next antidepressant and antipsychotic drugs, some of the latter having long-acting injectable preparations. An interesting event was a demonstration of the antidepressant activity of ketamine. My research domain in psychopharmacology was lithium treatment of affective illnesses. Lithium makes the topic of many papers I authored, more than 150 of them are in the PubMed database. Many clinical and research aspects related to lithium administration have been reported as first in Polish literature and some are pioneering in the world. Recently, I wrote the book Lithium - the amazing drug in psychiatry which has also its English version. I have carried much research on antidepressant drugs, pharmacotherapy of treatment-resistant depression, and mood-stabilizing drugs for which I proposed a modern classification. I participated in European projects EUFEST and OPTIMISE on the optimization of using antipsychotic drugs in schizophrenia. I also performed much research on the antidepressant effect of ketamine and electroconvulsive therapy.

A History of the Pharmacological Treatment of Bipolar Disorder.

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

La aventura del litio / The adventure of lithium

Lithium has been the major cause of the psychopharmacological revolution in the treatment of mood disorders. Discovered nearly 200 years, throughout its history, has had several therapeutic uses. The research conducted by Cade and Schou allowed its final incorporation in the therapeutic arsenal, emphasize its antidepressant effect, prevention of relapse in bipolar disorder and suicidal behavior. Its main indication is treat diverse stages of manic depressive psychosis. Although various side effects have been discovered, the cost / benefi t of lithium use, despite their lack of knowledge caused by the pharmaceutical industry, have led it grow progressively in clinical practice worldwide.

El litio ha sido el mayor causante de la revolución psicofarmacológica en el tratamiento de los trastornos del estado de ánimo. Descubierto hace casi 200 años, a lo largo de su historia, ha tenido diversos usos terapéuticos. Las investigaciones realizadas por Cade y Schou permitieron su incorporación definitiva en el arsenal terapéutico, destacando su efecto antidepresivo, la prevención de recaídas en bipolares y la de conductas suicidas. Su indicación principal es tratar diversas fases de la psicosis maniaco- depresiva. Aunque se han descubierto diversos efectos secundarios, el costo/beneficio del uso del litio, pese a su escasa difusión debida a por parte de la industria farmacéutica, lo ha llevado a crecer progresivamente en la práctica clínica a nivel mundial.

Jewels in the crown: The Medical Journal of Australia's 10 most-cited articles.

According to data from the Institute for Scientific Information (ISI), the most-cited MJA article is Cade's ground-breaking report on the effect of lithium in mania (1949; 888 citations), followed by Marshall et al's reports on the role of Helicobacter pylori in gastroduodenal disease (1985; 766 and 523 citations, respectively). Others in the "top 10" span decades and disciplines; all have a common grounding in Australian data of global relevance.

[Psychopharmacotherapy in the 20th century]. / Psychopharmakotherapie im 20. Jahrhundert.

Neuroleptics, antidepressants, mood stabilizers and anxiolytics are the most frequently prescribed drugs in psychiatric therapy. Their introduction came largely in the past five decades. This review summarizes the history that led to their discovery and introduction to the market in the 20th century.

Lithium revisited: savings brought about by the use of lithium, 1970-1991.

BACKGROUND: Recent estimates of the cost of manic-depressive illness totaled roughly $45 billion in 1991. Using data from the Epidemiological Catchment Area (ECA) study, this study estimates the savings brought about by the use of lithium between 1970 and 1991. METHODS: Total savings are the difference between estimated actual costs and projected costs had lithium never been introduced. Actual yearly costs were interpolated from data for 1970 and 1991, and projected costs were obtained by adjusting 1970 costs with Consumer Price Index (CPI) and population inflaters. All costs for 1970 were obtained using methods almost identical to those used to calculate the 1991 costs of manic-depressive illness, presented in a previous publication. All savings are presented in 1991 dollars. RESULTS: Between 1970 and 1991, lithium saved over $170 billion, or roughly over $8 billion per year. Approximately $15 billion in direct costs, which included inpatient and outpatient care as well as research, was saved between 1970 and 1991. The savings are more dramatic for indirect costs, which include the lost productivity of wage-earners, homemakers, family caregivers, and individuals who are in institutions or who committed suicide; these totaled roughly $155 billion. CONCLUSIONS: Our results suggest that, although manic-depressive illness is still costly, lithium has been tremendously successful in treating the illness, and has provided enormous financial savings in the process.

Inositol, lithium, and the brain.

This review of the background and present state of knowledge of the interactions of inositol metabolism and lithium commemorates the 150th anniversaries of the discovery of inositol and, independently, of first attempts to use lithium as a therapeutic agent. We review the inositol depletion hypothesis, which proposes that lithium's beneficial action in the treatment of bipolar disorder is attributable to its inhibition of the enzymatic breakdown of inositol phosphates to free inositol. A resulting reduction in free intracellular inositol is proposed to slow the recycling of inositol-containing metabolites required for signal transduction. We offer an alternative hypothesis, which is also based on lithium's blockade of inositol phosphatase, but proposes that neural signal transduction is suppressed as a consequence of lithium-induced inositol phosphate accumulation rather than of inositol depletion.

The psychopharmacologic specificity of the lithium ion: origins and trajectory.

This article examines the development of lithium therapy since its dramatic introduction into psychiatry in 1949. Since that time, lithium has been examined in the treatment of a variety of neuropsychiatric conditions, but it is in the treatment of bipolar disorder that it is most effective. This suggests that it has specificity in the treatment of this disorder. These findings are very relevant as they suggest that understanding the mechanism of action of lithium in bipolar disorder may hold keys to elucidating its pathophysiology and to developing newer and more effective treatments. We review the published data on the effectiveness of lithium in bipolar disorder and various neuropsychiatric conditions and also the available data on anticonvulsants and newer therapeutic agents in the treatment of this condition.