Sixty Years of Lithium Responders

Abstract

It has been 60 years since Cade first described patients who responded to antimanic lithium treatment. Two decades later, responders to lithium stabilization emerged in larger numbers. The responses of many severely ill bipolar patients to lithium were striking and called for an explanation. Remarkable reactions to a simple ion generated hope for an uncomplicated laboratory test of response and an extensive search for suitable biological markers ensued. But despite promising reports, particularly from molecular genetics, we are still waiting for a biological elucidation of the stabilizing effects of lithium. The most useful predictor of lithium stabilization has to date been the patient’s clinical profile, based on a comprehensive clinical assessment: complete remissions and other characteristics of episodic clinical course, bipolar family history, low psychiatric comorbidity and a characteristic presenting psychopathology. In brief, the responders approximate the classical Kraepelinian description of a manic-depressive patient. But the most intriguing findings have recently emerged from prospective observations of the next generation: the children of lithium responders, their counterparts coming from parents who did not respond to lithium and controls. Overall, they indicate that parents and offspring suffer from a comparable brain dysfunction that manifests clinically in distinct stages. If the child’s predicament starts early in childhood, it presents with varied, nonaffective or subclinical manifestations that are usually nonresponsive to standard treatments prescribed according to the symptoms. The next stage then unfolds in adolescence, first with depressive and later with activated episodes. The observations have a potential to markedly enrich the prevailing understanding and management of mood disorders.

Lithium Reduces Pathological Aggression and Suicidality: A Mini-Review

“…One of the lightest metallic elements had a heavy impact on the concepts and practice of modern psychiatry. Some scientific studies on lithium and clinical experience collected during recent decades partly confirmed early anecdotal findings, and partly remodeled and integrated them into updated, more precise and comprehensive concepts, thus making previous observations better understood [1,2] . Other studies detected or redetected important aspects of lithium which either are still to be discussed on a hypothetical level such as its 'neuroprotective' effects, or which are supported by very good scientific evidence but still did not find their way into everyday clinical practice and existing guidelines.…”

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

“…Further, the family history typically includes recurrent mood disorders, not chronic psychotic illnesses. 10,44,45 Granted there are intermediate clinical presentations and reports of overlapping genetic and neurobiological findings; however, in part this reflects the broadening of the BD concept 20,46 and assortative mating. 47,48 Another challenge to the proposal of simply generalizing the early psychosis model to mood disorders is that BD is not diagnosed until the manifestation of the first-activated (hypomanic or manic) episode; however, the classical disorder almost always starts with depressive episodes.…”

Psicofarmacología del suicidio II parte: Estabilizadores del ánimo y suicidio

“…Otro aspecto es la heterogeneidad de las poblaciones clínicas, constituyendo uno de los mayores obstáculos en la obtención de resultados "limpios" y más objetivos 32 . Los posibles mecanismos de acción específicos para el litio se citan en Tabla 1.…”