A case of generalized ostraceous psoriasis mimicking dermatitis neglecta

Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the induction of psoriasis on previously uninvolved skin of psoriasis patients, and in the triggering of psoriasis for the first time in patients without a personal or family history. Lithium-induced psoriasis (and its resistance to treatment) is one of the major reasons for noncompliance in patients treated with lithium. We describe a male patient who developed generalized ostraceous psoriasis whose clinical appearance mimicked dermatitis neglecta, 10 months after starting therapy with lithium.

The Structural and Functional Changes Indcuced By Lithium on The Renal Cortex of Growing Albino Rats: Ultrastructure and Laboratory Study.

Introduction: Lithium is a therapeutic agent currently used for the treatment of aff ective disorders controlling a variety of neurotic and psychosomatic manic depressions. Th e main objective of the present work was to demonstrate the histopathological eff ects of the therapeutic doses of Lithium on the renal tubules and glomeruli in growing albino rats. Material and Methods: Th irty growing male Sprague – Dawley albino rats were used in this study. Th e rats were divided into a control group formed of 6 rats and an experimental group formed of 24 rats which received a daily therapeutic dose of 20 mg Lithium/kg body weight by the same route for 7 weeks. Th e renal cortex in all animals is examined by light and electron microscopes. Blood was collected from the sacrifi ced animals for serum creatinine, urea, sodium and potassium to access the eff ect of lithium administration in a therapeutic dose on renal function. Results: Th e present work revealed that the therapeutic doses of Lithium induced nephrotoxicity in the form of degeneration and necrosis in the renal tubules and glomeruli. Alteration in the cellular fi ne structure and degenerated cytoplasm and cytoplasmic organelles were found revealing cellular degeneration and necrosis. Glomerulosclerosis and congestion were the predominant eff ect on the renal glomeruli. Conclusion: Histological and ultrastructrual features of Lithium nephrotoxicity were detected in the current study with therapeutic doses of Lithium.

Lithium safety and tolerability in mood disorders: a critical review / Tolerabilidade e segurança do lítio em transtornos do humor: uma revisão crítica

Background: Lithium is a first-line treatment for bipolar disorder in all phases, also indicated as add-on drug for unipolar depression and suicide prevention. This study encompasses a broad critical review on the safety and tolerability of lithium for mood disorders. Methods: A computerized search for English written human studies was made in MEDLINE, using the keywords “lithium” and “mood disorders”, starting from July 1993 through July 2013 (n = 416). This initial search aimed to select clinical trials, prospective data, and controlled design studies of lithium treatment for mood disorders reporting adverse effects (n = 36). The final selection yielded 91 studies. Results: The most common general side effects in patients on lithium treatment were thirst, frequent urination, dry mouth, weight gain, fatigue and cognitive complaints. Lithium users showed a high prevalence of hypothyroidism, hyperparathyroidism, and decrease in urinary concentration ability. Reduction of glomerular filtration rate in patients using lithium was also observed, but in a lesser extent. The evidence of teratogenicity associated with lithium use is not well established. Anti-inflammatory non-steroidal drugs, thiazide diuretics, angiotensin-converting enzyme inhibitors, and alprazolam may increase serum lithium and the consequent risk for intoxication. Discussion: Short-term lithium treatment is associated with mild side effects. Medium and long-term lithium treatment, however, might have effects on target organs which may be prevented by periodical monitoring. Overall, lithium is still a safe option for the treatment of mood disorders...

Contexto: O lítio é um tratamento de primeira linha para o transtorno bipolar, em todas as fases, e também é indicado como terapia adjunta para a depressão unipolar e prevenção do suicídio. Este estudo abrange uma ampla revisão crítica sobre a segurança e a tolerabilidade do lítio para transtornos do humor. Métodos: Uma busca informatizada para estudos com humanos escritos em inglês foi feita no MEDLINE, usando as palavras-chave “lítio” e “transtornos de humor”, a partir de julho de 1993 a julho de 2013 (n = 416). Esta pesquisa inicial teve como objetivo selecionar ensaios clínicos, estudos prospectivos e estudos controlados com tratamento com lítio para transtornos de humor, relatando efeitos adversos (n = 36). A seleção final identificou 91 estudos. Resultados: Os efeitos colaterais mais comuns nos pacientes em tratamento com lítio foram sede, micção frequente, boca seca, ganho de peso, fadiga e queixas cognitivas. Usuários de lítio mostraram uma alta prevalência de hipotireoidismo, hiperparatireoidismo e diminuição da capacidade de concentração urinária. Também foi observada redução da taxa de filtração glomerular em pacientes utilizando lítio, mas em menor grau. A evidência de teratogenicidade associada com o uso de lítio não está bem estabelecida. Os medicamentos anti-inflamatórios não esteroides, diuréticos, inibidores da enzima de conversão da angiotensina e alprazolam podem aumentar o lítio sérico e o consequente risco de intoxicação. Conclusões: O tratamento de curto prazo com lítio está associado com efeitos colaterais leves. No entanto, tratamentos de médio a longo prazo com lítio podem ter efeitos sobre órgãos-alvo que podem ser prevenidos por acompanhamento periódico. Em geral, o lítio é ainda uma alternativa segura para o tratamento dos transtornos de humor...

El litio y su relación con la acuaporina-2 y el canal de sodio ENaC / Lithium and its relation with the epithelial sodium channel and aquaporin-2

Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epitelial de sodio sensible al amiloride (ENaC) localizado en la membrana apical de la célula. Luego de 10- 20 años de tratamiento con litio los enfermos pueden desarrollar poliuria, acidosis tubular e insuficiencia renal crónica que puede terminar en una forma de diabetes que no responde a la arginina vasopresina llamada diabetes insípida nefrogénica. Se cree que estas fallas renales son consecuencias de una reducción en el número de moléculas de acuaporina 2 en la membrana apical. Las causas para esto son complejas. El litio es un poderoso inhibidor de la isoforma beta de la enzima glicógeno sintetasa quinasa y esto está asociado a una menor actividad de la adenilato ciclasa que lleva a una disminución en la concentración intracelular de cAMP. Esto finalmente interferiría con la síntesis de nuevas moléculas de acuaporina 2 y con el tráfico de ellas desde la zona subapical de la célula hacia la membrana celular, causando la disminución en la reabsorción de agua en la parte distal del nefrón.

For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in the collecting duct's principal cells through the epithelial Na channel (ENaC) located on the apical side of the cells. Polyuria, renal tubular acidosis and chronic renal failure are the most frequent adverse effects of lithium after 10-20 years of treatment and these alterations can reach to a vasopressin nonresponding form of diabetes insipidus entity called nephrogenic diabetes insipidus. It is believed that the molecular mechanisms of these renal changes are related to a reduction in the number of aquaporin-2 inserted in the apical membrane of the cells. The causes of this are complex. Lithium is a powerful inhibitor of the enzyme glycogen synthase kinase 3β and this is associated with a lower activity of adenylate cyclase with a reduction in the cAMP levels inside of the cells. The latter may interfere with the synthesis of aquaporin-2 and also with the traffic of these molecules from the subapical site to membrane promoting the impairment of water reabsorption in the distal part of the kidney.

Efeito do lítio sobre a hiperatividade locomotora induzida pela lesão eletrolítica da região do núcleo mediano da rafe em ratos / Effect of lithium treatment on the locomotor hyperactivity induced by the lesion of the region of the median raphe nucleus in rats

A lesão do núcleo mediano da rafe (NMR) produz sintomas que sugerem validade de face ao episódio maníaco. Esta pesquisa avaliou o efeito do lítio sobre a hiperatividade locomotora induzida por esta lesão. Vinte e um ratos Wistar machos foram submetidos à lesão eletrolítica da região do NMR (LR) e 17 foram submetidos à lesão fictícia (LF). Após recuperação, a atividade locomotora foi avaliada na caixa de atividade (Med Associates/ENV-515). Parte dos animais destes grupos recebeu tratamentos com lítio (47,5 mg/kg/2x dia i.p.) por 10 dias, enquanto o restante foi tratado com salina no mesmo esquema. A reavaliação ao final dos tratamentos demonstrou que o lítio reduziu significantemente a atividade locomotora em relação à avaliação inicial no grupo LR (ANOVA/Bonferroni p < 0,05), tornando-a equivalente aos baixos níveis dos grupos LF. Estes dados sustentam a hipótese de que as manifestações induzidas pela lesão do NMR podem constituir um modelo animal de mania.

The lesion of the Median Raphe Nucleus (MRN) produces symptoms that suggest face validity for manic episodes. This research evaluated the effect of lithium treatment on the locomotor hyperactivity induced by this lesion. Twenty-one Wistar male rats were submitted to the lesion of the region of the MRN (LR) and 17 were sham lesioned (LF). After recovery, the locomotor activity was evaluated in an activity chamber (Med Associates/ENV-515). A subgroup received lithium (47.5 mg/kg/twice a day i.p.) for 10 days, while the other animals received saline in the same schedule. The reevaluation at the end of the treatments showed that only lithium significantly reduced the activity of LR group compared to baseline levels (ANOVA/Bonferroni p < 0.05), making it equivalent to low levels of LF groups. These data support the hypothesis that the behavioral manifestations induced by the lesion of the MRN may constitute an animal model of mania.

Vias intracelulares da ação do Sildenafil no diabetes insipidus induzido pelo lítio / Sildenafil action in lithium-induced NDI: intracellular pathway

Os pacientes que usam lítio (Li) para tratamento do transtorno bipolar frequentemente apresentam poliúria e deficiência de concentração urinária, sintomas do Diabetes Insipidus Nefrogênico (DIN). Animais tratados com Li apresentam baixos níveis de produção de adenosina monofosfato cíclico (AMPc) em resposta ao hormônio antidiurético (HAD). O Sildenafil (Sil), um inibidor da fosfodiesterase 5 (PDE5), eleva os níveis intracelulares de guanosina monofosfato cíclico (GMPc), levando a inserção de aquaporina 2 (AQP2) na membrana plasmática das células do ducto coletor. Portanto, inibidores de PDE podem promover a inserção de AQP2 na membrana plasmática mesmo sem a ativação do receptor de HAD, indicando a participação de uma via alternativa mediada pelo GMPc. Nós investigamos as vias de ação do Sil no tratamento da DIN induzida pelo Li. Ratos Wistar foram divididos nos seguintes grupos: grupo controle, recebendo dieta alimentar normal durante quatro semanas; grupo Li, recebendo dieta alimentar normal com 40 mmol Li por quilo de dieta durante quatro semanas; grupo Li + Sil, recebendo dieta alimentar normal com 40 mmol Li por quilo de dieta durante quatro semanas e 200 mg por quilo de dieta de Sil a partir da segunda semana; grupo Sil, recebendo dieta alimentar normal durante a primeira semana e a partir da segunda semana recebendo dieta normal com 200 mg de Sil por quilo de dieta. Os animais do grupo Li desenvolveram poliúria, diminuição da osmolalidade urinária e diminuição da expressão da AQP2 tanto na fração citoplasmática como de membrana celular e o Sil reverteu essas alterações. Demonstramos ainda que a concentração de GMPc intracelular estava aumentada nos túbulos papilares tratados com Sil. Observamos que a provável via de fosforilação da AQP2 induzida pelo GMPc é pela PKA. Além disso, o tratamento com Sil aumenta a expressão de pCreb, fator de transcrição para ativação do gene da AQP2. Observamos ainda que o Li diminui a expressão de eNOS e o...

Patients taking lithium to treat bipolar disorder often present polyuria and urinary concentrating defect. In addition, lithium-treated animals present lower cyclic adenosine monophosphate production in response to vasopressin. Sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, elevates intracellular cyclic guanosine monophosphate (cGMP) levels, leading to plasma membrane accumulation of aquaporin 2 (AQP2). Therefore, PDE inhibitors might induce AQP2 membrane insertion even without vasopressin receptor activation by activating a parallel cGMP-mediated signal transduction pathway. We investigated Sil pathways of action in rats with lithium-induced nephrogenic Diabetes Insipidus (NDI). Wistar rats received lithium (40 mmol/kg food) or not for 4 weeks (Li or control), some rats also receiving sildenafil (200 mg/kg food) in weeks 2-4, with or without lithium (Li+Sil orSil). Animals in Li group developed polyuria, decreased urinary osmolality and decreased expression of AQP2 in both the cytoplasmic fraction and the cell membrane and Sil reversed these changes. We also demonstrated that intracellular cGMP concentration was increased in papillary tubules treated with Sil. We found that PKA may be involved in the pathway of cGMP induced AQP2 phosphorylation. In addition, Sil treatment increases Creb phosphorylation. Creb phosphorylation, acts as AQP2 gene transcription factor. We also observed that Li decreases eNOS expression and treatment with Sil normalizes this alteration. We conclude that Sil treatment improves polyuria by increasing production and insertion of AQP2. Sil treatment may be beneficial to patients suffering from induced DIN Li.

Nefrotoxicidade por lítio / Lithium nephrotoxicity

O lítio é amplamente empregado na terapia do transtorno bipolar. Sua toxicidade renal inclui distúrbio na capacidade de concentração urinária e natriurese, acidose tubular renal, nefrite túbulo-intersticial evoluindo para doença renal crônica e hipercalcemia. O efeito adverso mais comum é o diabetes insipidus nefrogênico, que acomete de 20 por cento-40 por cento dos pacientes semanas após o início do tratamento. A nefropatia crônica correlaciona-se com a duração do uso de lítio. A detecção precoce de disfunção renal deve ser feita através de monitoração rigorosa dos pacientes e colaboração entre o psiquiatra e o nefrologista. Recentes trabalhos experimentais e clínicos começam a esclarecer os mecanismos pelos quais o lítio induz alteração da função renal. No presente trabalho, objetivamos revisar a patogênese, a apresentação clínica, os aspectos histopatológicos e o tratamento da nefrotoxicidade induzida pelo lítio.

Lithium is widely used in the therapy of bipolar disorder. Its toxicity includes urinary concentration deficit and natriuresis, renal tubular acidosis, tubulointerstitial nephritis which complicates with chronic kidney disease and hypercalcemia. The most common adverse effect is diabetes insipidus, which occurs in 20-40 percent of patients some weeks after initiation of treatment. Such chronic nephropathy correlates with duration of lithium use. Early detection of renal dysfunction should be achieved by rigorous monitoring of patients and collaboration between the psychiatrist and nephrologist. Recent experimental and clinical studies are now clarifying the mechanisms by which lithium induces renal abnormalities. The aim of this work is to review the pathogenesis, clinical presentation, histopathologic aspects and treatment of lithium nephrotoxicity.

El litio y su influencia en la función tiroidea / Lithium and the influence in thyroid function

El Litio, utilizado como tratamiento de primera línea en la enfermedad maníaco depresiva, genera cambios en la fisiología tiroidea. En los últimos trabajos entre los años 1999 y 2007, se ha encontrado una alta prevalencia de hipofunción tiroidea en pacientes bipolares principalmente en el sexo femenino y a mayor edad. Aparentemente su aparición no se correlaciona con la duración del tratamiento ni con la Litemia. Dada la escasa literatura existente acerca de este tema, el objetivo de esta revisión es actualizar los datos últimamente publicados.

Lithium, used as a first line treatment in maniac depression disease, affects the thyroid gland function. In the last papers published between 1999 and 2007, it has been found a high prevalence of hypothyroidism in bipolar patients, especially in females and when starting lithium at a later age. The duration of treatment and Lithemia seams to have no correlation with the begining of hypothyroidism. Because of the poor literature written about this issue, the aim of this review is to update the last papers published.

Efectos crónicos y tratamiento con litio sobre la anatomía y función renal / Chronic effects of lithium treatment in renal anatomy and function

Lithium is a drug widely used in clinical psychiatry, often as first-line treatment. However, it has generated much controversy because of the likely adverse effects of both acute and chronic use, mainly in the kidney. With respect to prolonged exposure to lithium, it would be detrimental to the kidneys at variable extent, depending on factors such as duration of treatment, dosage of drug, patient age, renal damage, prior comorbidities, among others not yet sufficiently elucidated. The principal mechanism of renal function changes was determined by morphological changes, such as interstitial nephritis, interstitial-medullar fibrosis and tubular atrophy, all irreversible phenomena that ultimately lead to a tubuloglomerular imbalance and commitment of the GFR. Other aspects of chronic nephropathy induced by lithium and their production mechanisms are being studied, also the search and advanced diagnostic techniques to predict and / or detect early changes. Among them have described the pathology (renal biopsy), although this form of diagnosis is very late. Thus it seeks the introduction of imaging and serological markers of kidney failure as tools that provide information about kidney condition earlier.

El Litio es un fármaco ampliamente utilizado en psiquiatría, muchas veces como tratamiento de primera línea. Existe en la actualidad una activa controversia acerca de sus probables efectos adversos a nivel renal, tanto agudos como crónicos, ya que la exposición prolongada al Litio sería deletérea para el riñón en una magnitud variable, dependiendo de factores como duración del tratamiento, dosis del fármaco, edad del paciente, daño renal previo y comorbilidad, entre otros aún no suficientemente dilucidados. El origen del mecanismo principal de alteración de la función renal estaría en alteraciones morfológicas como la Nefritis Intersticial, la Fibrosis Intersticio-Medular y la Atrofia Tubular, todos fenómenos irreversibles que finalmente conducirían a un desbalance tubuloglomerular y a un compromiso de la VFG. Otros aspectos de la Neuropatía Crónica inducida por Litio y de sus mecanismos de producción se encuentran en estudio, así como también la búsqueda y perfeccionamiento de técnicas diagnósticas que permitan predeciry/o detectar tempranamente los cambios mencionados. Entre estas últimas se ha descrito la anatomía patológica (biopsia renal), aunque esta es una forma de diagnóstico muy tardía. Es por ello que se busca la introducción de la imagenología y de marcadores serológicos de falla renal como herramientas que entreguen información sobre la condición del riñón más precozmente.

Estudo da ação do inibidor de fosfodiesterase (sildenafil) no diabetes insipidus induzido pelo lítio / Role of phosphodiesterase inhibitor(sildenafil) in lithium-induced diabetes insipidus

Os pacientes que usam lítio (Li) para tratamento do transtorno bipolar freqüentemente apresentam poliúria e deficiência de concentração urinária, sintomas do Diabetes Insipidus nefrogênico (DIN). Animais tratados com Li apresentam baixos níveis de produção de adenosina monofosfato cíclico (AMPc) em resposta ao hormônio antidiurético (HAD). O Sildenafil (Sil), um inibidor da fosfodiesterase 5 (PDE5), eleva os níveis intracelulares de guanosina monofosfato cíclico (GMPc), levando a inserção de aquaporina 2 (AQP2) na membrana plasmática das células do ducto coletor. Portanto, inibidores de PDE podem promover a inserção de AQP2 na membrana plasmática mesmo sem a ativação do receptor de HAD, indicando a participação de uma via alternativa mediada pelo GMPc. Nós investigamos o efeito do Sil na expressão renal das proteínas de membrana AQP2, UT-A1, NKCC2, NHE3, P-ENaC em ratos com DIN induzido pelo Li. Ratos Wistar foram divididos nos seguintes grupos: grupo controle, recebendo dieta alimentar normal durante quatro semanas; grupo Li, recebendo dieta alimentar normal com 40 mmol Li por quilo de dieta durante quatro semanas; grupo Li + Sil, recebendo dieta alimentar normal com 40 mmol Li por quilo de dieta durante quatro semanas e 200 mg por quilo de dieta de Sil a partir da segunda semana; grupo Sil, recebendo dieta alimentar normal durante a primeira semana e a partir da segunda semana recebendo dieta normal com 200 mg de Sil por quilo de dieta. Os animais do grupo Li desenvolveram poliúria, diminuição da osmolalidade urinária e diminuição da expressão da AQP2. No grupo Li+Sil, o Sil foi capaz de reverter parcialmente a poliúria, diminuir o clearance de água livre, aumentar a osmolalidade urinária e aumentar a expressão da AQP2. A expressão de UTA1 foi completamente normalizada com o tratamento com Sil. A expressão das proteínas NKCC2 e NHE3 apresentaram-se aumentadas no grupo tratado com Li, e o Sil não foi capaz de reverter tal alteração...

Patients taking lithium to treat bipolar disorder often present polyuria and urinary concentrating defect. In addition, lithium-treated animals present lower cyclic adenosine monophosphate production in response to vasopressin. Sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, elevates intracellular cyclic guanosine monophosphate (cGMP) levels, leading to plasma membrane accumulation of aquaporin 2 (AQP2). Therefore, PDE inhibitors might induce AQP2 membrane insertion even without vasopressin receptor activation by activating a parallel cGMP-mediated signal transduction pathway. We investigated the effect of sildenafil on renal expression of AQP2, UT-A1, sodium/hydrogen exchanger (NHE3), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), and the epithelial sodium channel alpha subunit (P-ENaC). Wistar rats received lithium (40 mmol/kg food) or not for 4 weeks (Li or control), some rats also receiving sildenafil (200 mg/kg food) in weeks 2-4, with or without lithium (Li+Sil or Sil). In Li+Sil rats, urine output was markedly lower, as was water free clearance, whereas urine osmolality was higher. Semiquantitative immunoblotting revealed the following: AQP2 expression was partially normalized; UT-A1 expression was completely normalized; expression of NKCC2 and NHE3 was significantly higher in Li rats (although not significantly different between Li+Sil rats and Li rats); and P-ENaC protein expression was unaltered in all groups. Sildenafil treatment completely reversed the lithium-induced increase in renal vascular resistance. In conclusion, sildenafil treatment of lithium-induced nephrogenic diabetes insipidus (NDI) improves polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1. Sildenafil treatment could be beneficial in patients with lithium-induced NDI.

Efecto in vitro del litio sobre la excitabilidad de la preparación frenico-diafragma de rata y su relación con el temblor / In vitro effect of lithium on the excitability of rat phrenic nerve-diaphragm model and its relation with tremor

En la práctica clínica un común efecto adverso del litio es la aparición de temblor en reposo. Actualmente no existe una explicación satisfactoria de este fenómeno, por lo que se dificulta su manejo. El objetivo del presente estudio fue determinar el efecto del litio sobre la excitabilidad de la unión neuromuscular en una preparación in vitro, con el fin de dilucidar un mecanismo periférico que contribuya al entendimiento de la etiología del temblor inducido por litio. Para ello se expuso la preparación frénico diafragma de rata a concentraciones ascendentes de litio (0,25 mmol/l a 8 mmol/l). La preparación se sometió a estimulo directo e indirecto y se midieron, como indicadores de excitabilidad, la frecuencia de estímulo mínima necesaria para desencadenar un tétanos perfecto, el voltaje mínimo necesario para generar una respuesta regular y la presencia de actividad espontánea de la preparación. El grupo control se sometió al mismo tiempo al protocolo de estimulación en ausencia de litio. Se utilizaron pruebas no paramétricas para evidenciar diferencias significativas. Se observó un aumento en la frecuencia de estímulo mínima necesaria para desencadenar un tétanos perfecto, comparada con el control, tanto con estimulación directa (p=0) como indirecta (p=0,014); no se observó un cambio significativo en el voltaje mínimo necesario para generar una respuesta regular, ni se observó actividad espontánea en la preparación. Los resultados nos permitieron concluir que el litio no aumenta la excitabilidad de la preparación neuromuscular in vitro y, por lo tanto, no predispone a la aparición de temblor, lo cual sugiere que el temblor no se explica por un mecanismo periférico

Cardiovascular effects of antidepressants and mood stabilizers

Depression is a serious disorder in today's society, with the estimates of lifetime prevalence being as high as 21% of the general population in some developed countries. As defined by the American Psychiatric Association, depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. Such patients are often reluctant to take synthetic antidepressants in their appropriate doses due to their anticipated side effects including inability to drive a car, dry mouth, constipation, and sexual dysfunction. As a therapeutic alternative, effective herbal drugs may offer advantages in terms of safety and tolerability, possibly also improving patient compliance. The advent of the first antidepressants, Monoamine Oxidase Inhibitors [MAOIs] and Tricyclic Antidepressants [TCAs], in the 1950s and 1960s represented a dramatic leap forward in the clinical management of depression. The subsequent development of the Selective Serotonin Reuptake Inhibitors [SSRIs] and the Serotonin Norepinephrine Reuptake Inhibitor [SNRI] venlafaxine in the past decade and a half has greatly enhanced the treatment of depression by offering patients medications that are as effective as the older agents but are generally more tolerable and safer in an overdose. The introduction of atypical antidepressants, such as bupropion, nefazadone, and mirtazapine, has added substantially to the available pharmacopoeia for depression. Nonetheless, rates of remission tend to be low and the risk of relapse and recurrence remains high. One of the concerns regarding the safety of antidepressant is its potential risk of cardiotoxicity and cardiovascular side effects. In this review, we will focus on the cardiovascular side effects of different types of antidepressants

Psychotropics in pregnancy: weighing the risks.

With increase in the use of newer psychotropics, there is a growing concern in relation to the teratogenicity. Unfortunately, it is not possible to carry out prospective studies in pregnant women and as a result physicians caring for such patients have to rely on case reports, case series, and retrospective studies. Available evidence shows that the safety of psychotropics in pregnancy is still unresolved and the decision to prescribe psychotropics in pregnancy should be taken in the light of severity of mental disease, and drugs should be prescribed only when the potential risk to the foetus from exposure is outweighed by the risk of untreated maternal disorder. In this review we discussed the current evidence of the teratogenic risks with psychotropic drugs commonly used to treat psychiatric disorders and also focused on decision making in such patients.

A influência do lítio no risco para a doença de Alzheimer / The influence of lithium on the risk of Alzheimer's disease

O lítio é frequentemente utilizado no tratamento do transtorno bipolar, doença associada a um risco aumentado para demência. Evidências experimentais sugerem efeitos neuroprotetores do lítio. O lítio inibe a amiloidogênese e a fiosforilação da proteína tau tanto in vitro como in vivo. Estes são processos importantes na patogênese da doença de Alheimer. O objetivo deste estudo foi a investigação do efeito do litio na prevalência / Lithium is widely used in the treatment of bipolar disorder, a condition associated with an increased risk for dementia. Experimental evidence suggests that lithium has a neuroprotective effect. Both in vitro and in vivo, lithium inhitis amyloidogenesis and phosphorilation of thau protein, wich arre two crucial processes in the pathogenesis of Alzheimer's disease...

Histological study on withdrwal of chronic lithium therapy on rabbits thyroid

Sixty male adult albino rabbits were divided into two groups, control and experimental. Each group was divided into three sub-groups. Lithium Carbonate powder 34.2 mg per kg body weight was administered daily by oral route in the form of capsule for four weeks to the experimental group. The control group was given empty capsule and normal diet. Animal weight and serum lithium levels were measured at the beginning of the experiment and were checked weekly. After four weeks, one third of the animal in each group were sacrificed and thyroid were examined to see the affect of drugs on them. Second group was sacrificed after one week of withdrawal and third group after two weeks of withdrawal. The serum lithium levels drop significantly after two weeks of withdrawal but did not reach the base line. There was significant increase in the weight of the animals, weight and relative tissue weight index of the thyroid, mostly due to congestion as hyperplasia and hypertrophy seen after two weeks of withdrawal had no significant increase as compared to the other experimental groups. Therefore, significant increase in weight of thyroid after two weeks of withdrawal can be attributed to persisting lithium in tissues or rebound phenomenon

Lithium - Induced Nephrogenic Diabetes insipidus

We report a case of a 43 year-old female who presented with lithium-induced nephrogenic diabetes insipidus. This patient had history of bipolar disorder for which she had been taking lithium carbonate for last 16 years. Appropriate work up was done and she was diagnosed with nephrogenic diabetes insipidus, secondary to lithium toxicity, and was managed accordingly

Delirium and Extrapyramidal Symptoms Due to a Lithium-Olanzapine Combination Therapy: A Case Report

We report an elderly patient who developed severe delirium and extrapyramidal signs after initiation of lithium-olanzapine combination. On hospital admission, serum levels of lithium were found to be 3.0 mM/L which were far above toxic level. Immediate discontinuation of both drugs resulted in complete resolution of most of the symptoms except for perioral dyskinesia which persisted for three more months. We critically discussed the differential diagnosis of lithium intoxication and assessed confounding factors which induce delirium and extrapyramidal signs related with combination therapy of lithium and olanzapine.

Lithium - induced tardive dystonia.

Tardive dystonia is an uncommon form of chronic dystonia, which usually develops on exposure to neuroleptics. Tardive dystonia (Tdt) following lithium therapy has not been previously reported. The case of 38 year old man with bipolar affective disorder who developed tardive dystonia while on maintenance lithium treatment is described. Presentation of Tdt in this patient was fairly characteristic although there was no suggestion of recent neuroleptic exposure. Tdt known to have poor treatment response, responded very well to clozapine, a novel anti-psychotic, in this case. To conclude, Tdt may develop on exposure to drugs other than neuroleptics. An adequate trial to clozapine can prove to be a useful treatment option.