Update on the use and management of lithium in neuropsychiatry / Actualización en el uso y el manejo del litio en neuropsiquiatría.

Lithium is an alkaline metal, used for more than 60 years in psychiatry, and currently considered the gold standard in the treatment of bipolar disorder (BD). According to recent evidence, this active ingredient is useful for the treatment of a wide spectrum of clinical varieties of affective disorders. In addition, it is estimated that lithium reduces the risk of suicide and suicidal behavior in people with mood disorders. On the other hand, some novel studies have shown that the cation has a potential efficacy for the treatment of other neuropsychiatric processes, such as the likelihood of reducing the risk of dementia and slowing down the development of neurodegenerative diseases. Despite the enormous evidence in favor of the use of lithium, it is known that, in Argentina, medications containing it are prescribed less than expected. In view of all this, the Asociación Argentina de Psiquiatría Biológica (Argentine Association of Biological Psychiatry) (AAPB or AABP) convened a group of experts to review the available scientific literature and prepare an updated document on the management and use of lithium in neuropsychiatry. In addition to the use of the ion in daily clinical practice, the scope of this review includes other contents that have been considered of interest for the psychiatrist, such as certain pharmacological and pharmacogenetic aspects, possible clinical predictors of response to treatment with lithium, management of ion during perinatal period, management of lithium in child and adolescent population, management of adverse effects linked to cation and interactions with drugs and other substances.

El litio es un metal alcalino, usado hace más de 60 años en psiquiatría, y actualmente es considerado el estándar de oro en el tratamiento del trastorno bipolar (TB). De acuerdo con la evidencia reciente, este principio activo es útil para el tratamiento de un amplio espectro de variedades clínicas de los trastornos afectivos. Además, se estima que desde hace tiempo el litio reduce el riesgo de suicidio y de comportamiento suicida en personas con trastornos del estado de ánimo. Por otro lado, algunos estudios novedosos han demostrado que el catión posee una potencial eficacia para el tratamiento de otros procesos neuropsiquiátricos, tales como la probabilidad de disminuir el riesgo de demencia y la de ralentizar el desarrollo de enfermedades neurodegenerativas. A pesar de la enorme evidencia a favor de la utilización del litio, se sabe que, en la Argentina, las especialidades medicinales que lo contienen se prescriben menos de lo esperado. En virtud de todo lo mencionado, la Asociación Argentina de Psiquiatría Biológica (AAPB) convocó a un grupo de expertos para revisar la literatura científica disponible y elaborar un documento actualizado sobre el manejo y el uso del litio en neuropsiquiatría. Además de la utilización del ion en la práctica clínica diaria, el alcance de esta revisión incluye otros contenidos que se han considerado de interés para el médico psiquiatra, tales como ciertos aspectos farmacológicos y farmacogenéticos, posibles predictores clínicos de la respuesta al tratamiento con litio, el manejo del ion durante el período perinatal, el manejo de litio en la población infantojuvenil, el manejo de los efectos adversos vinculados con el catión y las interacciones con medicamentos y otras sustancias.

Third Argentine Consensus statement on management Bipolar Disorders. Section3: Bipolar Disorder in the context of special situations / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Tercera parte: Manejo de los Trastornos Bipolares en el contexto de situaciones especiales.

This document constitutes the third and last part of the Third Argentine Consensus on the Management of Bipolar Disorders carried out by the Argentine Association of Biological Psychiatry (AAPB). Continuing with the initial objective, this section of the Consensus on the Management of Bipolar Disorders is focused on the management of bipolar disorders in special populations. This section constitutes a comprehensive review and expert consideration of the scientific evidence on: a) the management of bipolar disorders in treatment-resistant patients; b) the management of bipolar disorder in childhood and adolescence; c) the management of bipolar disorders in women during their perinatal period and, d) the management of bipolar disorders in older adults.

Este documento constituye la tercera y última parte del Tercer Consenso Argentino sobre el Manejo de los Trastornos Bipolares llevada a cabo por la Asociación Argentina de Psiquiatría Biológica (AAPB). Siguiendo con el objetivo propuesto por el comité de expertos, en la actual versión del Consenso sobre el manejo de los trastornos bipolares, esta sección está enfocada al abordaje de los Trastornos Bipolares en situaciones especiales. Esto configura una revisión exhaustiva de la evidencia científica  sobre: a) el manejo de los trastornos bipolares en pacientes resistentes al tratamiento, b) el manejo de los trastornos bipolares en la mujer en el período perinatal, c) el manejo del trastorno bipolar en la etapa infantojuvenil y d) el manejo de los trastornos bipolares en los adultos mayores.

Third Argentine Consensus statement on management Bipolar Disorders. Section 2 B / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Segunda Parte B.

This document constitutes the second section B of the Third Argentine Consensus on the Management of Bipolar Disorders, focused on synthesizing the most updated evidence on therapeutic approaches for adult patients. The scope of this section is to provide therapeutic recommendations for managing bipolar disorders in adults, (i) acute mania (ii) bipolar depression (iii) mixed stated (iv) suicidality and (vi) psychological interventions. In addition, the current manuscript outlines the assessment and management of side effects of pharmacotherapeutic treatments.

Este documento constituye la segunda parte B del Tercer Consenso Argentino sobre el Manejo de los Trastornos Bipolares llevada a cabo por la Asociación Argentina de Psiquiatría Biológica (AAPB). Siguiendo con el direccionamiento iniciado en el parte 2A sobre el tratamiento integral de los trastornos bipolares, esta sección se ha enfocado en sintetizar la evidencia más actualizada sobre abordajes terapéuticos para pacientes adultos. El alcance de esta sección es proporcionar recomendaciones terapéuticas para el manejo de los trastornos bipolares en adultos, (i) manía aguda, (ii) depresión bipolar, (iii) estado mixto, (iv) el suicidio en el trastorno bipolar, (v) intervenciones psicológicas. Además, el presente manuscrito aborda la evaluación y el manejo de los efectos secundarios de los tratamientos farmacoterapéuticos.

Third Argentine Consensus statement on management Bipolar Disorders. Section 2 A: Comprehensive treatment of the bipolar disorders in adults / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Segunda Parte A: Tratamiento integral de los trastornos bipolares en el adulto.

This document constitutes the second section A of the Third Argentine Consensus on the Management of Bipolar Disorders, focused on synthesizing the most updated evidence on therapeutic approaches for adult patients. The aim of this section (2A) is to provide therapeutic recommendations for managing bipolar disorders in adults. In addition, the scope of this current manuscript outlines recommendations on the use of treatment guidelines, levels of evidence available to support these recommendations, general considerations for the treatment of bipolar disorders, the so-called pseudoresistance and adherence to treatment, general considerations on psychological therapies, as well as long term treatment of bipolar disorders.

Este documento corresponde a la segunda parte del Tercer Consenso Argentino sobre el manejo de los trastornos bipolares, enfocada en sintetizar la evidencia actualizada sobre los abordajes terapéuticos de esta patología en los pacientes adultos. Siguiendo la metodología descripta en la primera parte del Consenso, el panel de expertos realizó una exhaustiva revisión de la bibliografía y, como consecuencia de un posterior debate sobre la información disponible, se generó esta sección A del segundo documento que abarca el tratamiento integral de las personas adultas que padecen este trastorno. Durante la etapa de debate y discusión de estas guías, se decidió incorporar algunos puntos que estimamos serán de gran utilidad para el equipo interdisciplinario encargado del manejo de pacientes con trastornos bipolares.  En tal sentido, en la sección A de la segunda parte de este documento, se podrán encontrar las recomendaciones generales para el uso de las guías de tratamiento, los niveles de evidencia disponibles para sustentar las recomendaciones, las consideraciones generales del tratamiento de los trastornos bipolares, el fenómeno de pseudorresistencia y adherencia al tratamiento, las consideraciones generales sobre el abordaje psicológico, así como el tratamiento a largo plazo de los trastornos bipolares.

Paratonia, Gegenhalten and psychomotor hypertonia Back to the roots.

In the first half of the 20th century, well before the antipsychotic era, paratonia, Gegenhalten and psychomotor hypertonia were described as new forms of hypertonia intrinsic to particular psychoses and catatonic disorders. A series of astute clinical observations and experiments supported their independence from rigidity seen in Parkinson's disease. After World War II, motor disorders went out of fashion in psychiatry, with drug-induced parkinsonism becoming the prevailing explanation for all involuntary resistance to passive motion. With the 'forgetting' of paratonia and Gegenhalten, parkinsonism became the prevailing reading grid, such that the rediscovery of hypertonia in antipsychotic-naive patients at the turn of the 21st century is currently referred to as "spontaneous parkinsonism", implicitly suggesting intrinsic and drug-induced forms to be the same. Classical descriptive psychopathology gives a more nuanced view in suggesting two non-parkinsonian hypertonias: (i) locomotor hypertonia corresponds to Ernest Dupré's paratonia and Karl Kleist's reactive Gegenhalten; it is a dys-relaxation phenomenon that often needs to be activated. (ii) Psychomotor hypertonia is experienced as an admixture of assistance and resistance that partially overlaps with Kleist's spontaneous Gegenhalten, but was convincingly isolated by Henri Claude and Henri Baruk thanks to electromyogram recordings; psychomotor hypertonia is underpinned by "anticipatory contractions" of cortical origin, occurrence of which in phase or antiphase with the movement accounted for facilitation or opposition to passive motions. This century-old knowledge is not only of historical interest. Some results have recently been replicated in dementia and as now known to involve specific premotor systems.

Third Argentine Consensus statement on management Bipolar Disorders. Section1: introduction and general concepts / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Primera Parte: introducción, método de trabajo y generalidades.

The Third Argentine Consensus on the management of bipolar disorders (TB) is an initiative of the Argentine Association of Biological Psychiatry (AAPB). As a reference document, this consensus pursues two main objectives: on the one hand, to summarize and systematize the best available evidence on the comprehensive management of this pathology; on the other, to provide a useful, up-to-date instrument for psychiatrists, multidisciplinary teams dedicated to mental health, and government agencies. During a period of approximately six months of work -that is, from May to October 2022- a committee of experts made up of 18 professionals and representatives of the three most important Psychiatry and Mental Health associations in Argentina (that is, the AAPB, the Argentine Association of Psychiatrists, AAP, and the Association of Argentine Psychiatrists, APSA) have focused on updating the information regarding TB. Finally, this document was prepared as a result of an exhaustive review of the bibliography published to date, which was strategically divided into three parts: the first deals with the generalities of TB; the second deals with the comprehensive treatment of the pathology; finally, the third analyzes TB in the context of special situations.

El Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares (TB) es una iniciativa de la Asociación Argentina de Psiquiatría Biológica (AAPB). Como documento de referencia, este consenso persigue dos objetivos principales: por un lado, resumir y sistematizar la mejor evidencia disponible sobre el manejo integral de esta patología; por el otro, proporcionar un instrumento útil y actualizado a psiquiatras, a equipos multidisciplinarios abocados a la salud mental y a organismos gubernamentales. Durante un período de aproximadamente seis meses de trabajo -desde mayo a octubre de 2022- un comité de expertos integrado por 18 profesionales y por representantes de las tres asociaciones de Psiquiatría y Salud Mental más importantes de la Argentina: la AAPB, la Asociación Argentina de Psiquiatras, (AAP) y la Asociación de Psiquiatras Argentinos (APSA), se abocaron a actualizar la información respecto de los TB. Finalmente, y como resultado de una exhaustiva revisión de la bibliográfica publicada hasta la actualidad, se confeccionó este documento que fue dividido estratégicamente en tres partes: la primera versa acerca de las generalidades del TB; la segunda aborda el  tratamiento integral de la patología; y, por último, la tercera analiza los TB en el contexto de situaciones especiales.

[Argentine consensus on the diagnosis and therapeutics of treatment resistant schizophrenia]. / Consenso argentino sobre diagnóstico y tratamiento de la esquizofrenia resistente al tratamiento.

Approximately 30% of people with schizophrenia fail to respond to first-line antipsychotic treatment which impacts the burden of the disease. Treatment-resistant schizophrenia (TRS) denotes patients with failure to respond to at least two adequate trials of different antipsychotics. Clozapine is a unique drug approved for treating treatment-resistant schizophrenia, however 1/3 of patients fail to respond to clozapine. Even though different strategies have been proposed for treating clozapine-resistant schizophrenia, the evidence is very limited, unclear, and of poor quality. A formal literature search was conducted and then, panel members were asked to complete 35 questions addressing different aspects of TRS. A modified Delphi method was used to unify expert opinion and achieve consensus. The expert consensus in diagnostic and treatment of TRS is the result of experts from the main national scientific societies under the organization of the Argentine Association of Biological Psychiatric (AAPB). The consensus statement aims to guide on diagnosis and treatment.

Wernicke-Kleist-Leonhard phenotypes of endogenous psychoses: a review of their validity
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While the ICD-DSM paradigm has been a major advance in clinical psychiatry, its usefulness for biological psychiatry is debated. By defining consensus-based disorders rather than empirically driven phenotypes, consensus classifications were not an implementation of the biomedical paradigm. In the field of endogenous psychoses, the Wernicke-Kleist-Leonhard (WKL) pathway has optimized the descriptions of 35 major phenotypes using common medical heuristics on lifelong diachronic observations. Regarding their construct validity, WKL phenotypes have good reliability and predictive and face validity. WKL phenotypes come with remarkable evidence for differential validity on age of onset, familiality, pregnancy complications, precipitating factors, and treatment response. Most impressive is the replicated separation of high- and low-familiality phenotypes. Created in the purest tradition of the biomedical paradigm, the WKL phenotypes deserve to be contrasted as credible alternatives with other approaches currently under discussion.
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Severity of negative symptoms significantly affects cognitive functioning in patients with chronic schizophrenia: The slowing in cognitive processing

Background and Objectives: Studies in patients with schizophrenia have shown a decreased overall cognitive performance, and it was found that processing speed and working memory functions are affected. The aim of this study was to describe the general cognitive performance of patients with chronic schizophrenia and analyze its relationship with the severity of psychotic symptoms. Methods: Forty-eight patients diagnosed with DSM IV-TR schizophrenia disorder were examined for symptom improvement, measured by scales SAPS and SANS. Participants also completed the full scale WAIS-III. Results: The results show a generalized cognitive deficit, reflected in the low level of general intelligence, as well as the different index that comprise the scale. The most compromised index was the processing speed. The correlations showed that the overall severity of negative symptoms significantly affects cognitive functioning of chronic patients. The formal thought disorder and alogia significantly correlated with almost all the WAIS-III measures. Conclusions: Multiple studies of specific cognitive domains in schizophrenia have shown that deficits in processing speed are the core element of cognitive impairment in schizophrenia. We support the hypothesis about the slowing in cognitive processing affect both the performance of the basic and more complex cognitive task (AU)

Verbal fluency in chronic schizophrenia and severity of psychotic symptoms. Consideration of their relationship with errors in the tasks

Background and Objectives: There are many associations between psychotic symptoms and performance in Verbal Fluency (VF) tasks. However, most of these are found are with negative symptoms. In this study we examined the relationship between the performance in four VF tasks and the severity of both positive and negative symptoms. Methods: To compare performance in different VF tasks, two groups of participants were matched for age, sex and educational level, a Healthy Control Group (N = 83) and a Chronic Schizophrenia Group (N = 83). We examined the correlation between cognitive performance in these verbal tests and the severity of psychotic symptoms in the group of patients. Results: The results show that the performance of patients with chronic schizophrenia in VF tests is significantly lower than for healthy individuals. The analysis of correlations between tasks showed a significant correlation between the severity of negative symptoms and poor performance in VF tasks. Another interesting result was the association between the severity of formal thought disorder and poor performance in semantic VF. A particularly striking result was the correlation between the severity of positive symptoms and the number of errors in VF tasks in the patient group. Conclusions: These results have provided evidence for some of the proposed hypotheses and are in accordance with previous investigations. The correlations between the positive symptoms and the number of errors in the different VF tasks have not been previously reported. It is important to note that most of these correlations are between the severity of positive symptoms and intrusion errors (AU)

Attention in patients with chronic schizophrenia: Deficit in inhibitory control and positive symptoms

Background and Objectives: Attention is a central mechanism controlling information processing, activating and inhibiting processes, and forming a complex system including diferent networks in specific areas of the brain1. To correctly assess the role of attention in schizophrenia it is necessary to discriminate its different attentional components, which may by selectively altered. Attention span, focused attention, selective attention, sustained attention and inhibitory response, were assessed in patients with chronic schizophrenia and healthy matched controls. Methods: The study included 32 patients diagnosed with chronic schizophrenia and 32 healthy subjects. The groups were matched in age, sex, and level of education. Symptom severity (positive symptoms, negative symptoms, and general psychopathology) was assessed with the Scale for the Assessment of Positive and Negative Symptoms (SAPS and SANS). Attentional components were measured by Forward Digit Span, Symbol Search, Digit Symbol Coding, Stroop Test and Picture Completion. Results: Schizophrenic patients exhibited lower attentional scores in all tests compared to the control group. Inhibitory control and sustained attention were the most affected traits in schizophrenic patients. An inverse correlation was observed between inhibitory control and delusions and disorganized thinking. No significant correlations were observed between negative symptoms and attentional performance. Conclusions: The pattern of results obtained in this paper evidences the role of an inhibitory control deficit in patients with chronic schizophrenia that could also be involved in other attentional and cognitive failures, and also be connected to positive symptoms (AU)