Cutaneous adverse reaction during lithium treatment: a case report and updated systematic review with meta-analysis

OBJECTIVES: To present a new case of adverse cutaneous reaction during lithium treatment and to update the systematic review and meta-analysis of the incidence of this adverse reaction. METHODS: We conducted a systematic search (performed in September 2016) for peer-reviewed articles in English indexed in Medline (2011-present). Meta-analytical estimates were obtained using the "Metafor" package. CASE PRESENTATION: Ms. H., a 31-year-old Caucasian woman with BD1, was admitted to the inpatient unit for a full-blown psychotic episode and treated with carbamazepine 400 mg q.d., lithium carbonate 450 mg q.d., and risperidone 4 mg q.d. with clinical improvement. After 12 days from the start of psychopharmacological treatment, she manifested a cutaneous reaction that motivated the stop of carbamazepine treatment, as well as the increase in lithium carbonate dose (750 mg q.d.). Risperidone dose remained unvaried. Since the skin lesion persisted after 8 days from withdrawal of carbamazepine, the private practitioner stopped also lithium carbonate treatment (de-challenge), maintaining risperidone treatment. The cutaneous reaction resolved spontaneously after six days from withdrawal of lithium carbonate. Subsequently, the worsening of psychopathological conditions motivated a new admission during which lithium carbonate was reintroduced (16 days after its suspension) (re-challenge). On the following day, we observed an itching erythematous maculopapular rash involving the trunk, the four limbs, and the oral mucosa. CONCLUSIONS: Our case of an erythematous maculopapular rash during lithium treatment was the first to present a challenge-de-challenge-re-challenge sequence that suggests causality. Although meta-analysis does not point to an increased rate of adverse skin reaction during lithium treatment, clinicians should not neglect to monitor cutaneous symptoms during lithium treatment

Long-term treatment for bipolar disorders

Las indicaciones medicamentosas para el tratamiento del trastorno bipolar (TB) requieren de una ponderación de la necesidad de tratamiento del episodio en curso y su evolución a largo plazo. Los objetivos principales radicarán en estabilizar el ánimo, evitar un episodio de polaridad opuesta y prevenir posibles recaídas. Dentro del abanico de tratamientos disponibles se encuentran los estabilizadores del humor, los antipsicóticos, los antidepresivos, y las terapias no farmacológicas. En el presente trabajo se realiza un recorrido sobre las ventajas y desventajas de estos tratamientos. La evidencia empírica indica que el litio resulta el estabilizador del humor más utilizado siendo considerado como gold standard para la prueba de nuevos tratamientos. Los antipsicóticos suelen ser los fármacos de elección para episodios maníacos con o sin este tipo de síntomas y prefiriéndose a los atípicos por presentar menores efectos secundarios. El uso de antidepresivos debe ser cauteloso por el riesgo de polarización a estados maníacos. Finalmente, dentro de las terapias no farmacológicas, la terapia cognitivo conductual y la psicoeducación son consideradas las intervenciones más eficaces.Medical prescriptions for bipolar disorders require taking into account both episodic and long-term treatment. The main objectives will be mood stabilization, avoiding inducing an opposing episode and preventing of relapses. Treatments available include mood stabilizers, antipsychotics, antidepressants, and non- pharmacological therapies. This papers overviews advantages and disadvantages of those treatments. Empirical evidence indicates that lithium is the most widely used mood stabilizer being considered the gold standard for testing new treatments. Antipsychotics are usually used for treating manic episodes with or without that type of symptoms. Atypical antipsychotics are preferred for they present fewer side effects. The use of antidepressants must be cautious for they may induce a manic episode. Finally, behavioral cognitive therapy and psychoeducation prevail as the most effective interventions among non-pharmacological options

Multisite international collaborative clinical trials in mania.

Multi-regional collaborative clinical trials include those conducted across heterogeneous areas of the world under common protocols. Such trials appear to be driven primarily to provide data required for regulatory approval or licensing of new drug products in a relatively rapid and presumably efficient and cost-effective manner. Commonly, they include underserved populations and areas where costs of trials are lower than in most developed countries. In addition, such studies can potentially make innovative treatments widely and rapidly available in vast, international markets. Other potential benefits to collaborating sites may include diffusion of knowledge and improvement of research skills, as well as improvement of treatment and a broader salutary impact on health services and perhaps on employment opportunities and economic growth (Demol +6; Weihrauch, 1997; Glickman et al. 2009; Gopal et al. 2005; Greco +6; Diniz, 2008; ICH Guideline, 2002; Smulevich et al. 2005; U.S. FDA, 1998). Successful conduct of international trials requires compliance with varying local and international laws, regulations and ethical requirements, and confronting a range of systems of review of ethical aspects of subject recruitment, compensation, consenting procedures, research protocols, and provision of aftercare – all which can add complexity. In addition, there is variance among regions, countries and cultures in levels of education, and in the nature of information, financial inducements, clinical care and aftercare provided to research subjects. Complexities arise also from culture-dependent conceptualizations of mental disorders, criteria for diagnosis, and efforts at validating, interpreting and scoring of symptom ratings designed to characterize changes during treatment, and methods for detecting adverse events. In the continuing quest to define core or universal features of psychiatric disorders, it is crucial to consider the anthropological and cultural context in which they develop and are modified (Karno +6; Jenkins, 1993; Lopez-Ibor, 2003;

Lithium and bipolar depression

Kelly1 has recently disputed the recommendations of several international guidelines on the use of lithium in bipolar depression. In his scrutiny, the author points to three main errors that seem to have affected systematically ten international guidelines, namely the Woozle effect (evidence by citation), reference inflation (inappropriate citation of pivotal, generally old, studies) and belief perseverance (inability to modify evidence‐based recommendations despite the presence of contrary data). We concur with the author that the evidence supporting the effectiveness of lithium in acute bipolar depression, and to a lesser degree also in major depressive episodes, remains inadequate.2, 3 A different matter is, in our opinion, to label guidelines recommendations as inaccurate or biased, even if, as the author stated, no deceptive intentions were present

Olivine-lamproite from Ybytyruzú Lamproite Field, Eastern Paraguay

En el presente trabajo se realiza la descripción de la geología, la química mineral, comentarios sobre su geoquímica y caracterización de la intrusión Yzu-4 emplazada en el Campo de rocas lamproíticas del Ybytyruzú, Paraguay Oriental. De acuerdo a la petrografía y química mineral, con refuerzos de química de roca (elementos mayores, menores, trazas e isotopos de Sr y Nd), Yzu-4 se trata de una sanidina diopsido analcima, olivino lamproita expuesta junto a un inferido (a partir de imágenes de satélite Landsat 4-5 y 7) conducto alimentador (feeder) de una intrusión en forma de pipe de unos 900x900 metros de diámetro y que está situada a menos de 1500 metros de un otro conducto de olivino lamproíta rica en micas (también inferido como pipe diamantífera). El Campo de lamproítas del Ybytyruzú yace sobre el corazón Archon profundo del cratón Rio de la Plata.In the present work is carried out the description of geology, mineral chemistry,geochemistry, and characterization of the Yzu-4 intrusion that occurs in the Ybytyruzú lamproites field,Eastern Paraguay. According to the petrography and mineral chemistry, with reinforcements of rockchemistry (major, minor and traces elements and isotopes of Sr and Nd), Yzu-4 belongs to sanidinediopside analcime, olivine lamproite exposed next to a inferred (from Landsat 4-5 and 7 satellite imagery)pipe-shaped intrusion of 900x900 meters in diameter and located less than 1500 meters from anotherintrusion of diamond- bearing olivine lamproite rich in micas (also inferred as pipe). The Ybytyruzúlamproites field lies on the deep Archon heart of Rio de la Plata craton.Fil: Baez Presser, Jaime Leonardo. Jaime Presser Exploraciones; ParaguayFil: Vladykin, Nikolay V.. Institute Of Geochemistry; RusiaFil: Bitschene, Peter Rene. Museo Ciencias Naturales de Gerolstein; AlemaniaFil: Tondo, Matías J.. Universidad Nacional de Asunción; ParaguayFil: Acevedo, Rogelio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Alonso, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta; ArgentinaFil: Benitez, Pedro. Universidad Nacional de Asunción; Paragua

Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes

Introduction: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. Methods: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. Results: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). Conclusions: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples

Clinical use of lithium salts: guide for users and prescribers

Lithium has been used clinically for 70 years, mainly to treat bipolar disorder. Competing treatments and exaggerated impressions about complexity and risks of lithium treatment have led to its declining use in some countries, encouraging this update about its safe clinical use. We conducted a nonsystematic review of recent research reports and developed consensus among international experts on the use of lithium to treat major mood disorders, aiming for a simple but authoritative guide for patients and prescribers