Escitalopram-Induced Chronic Euvolemic Hyponatremia

Selective serotonin reuptake inhibitors (SSRIs), through the recent years have seen an increase in the number of prescriptions for a spectrum of mood disorders, especially in the geriatric population. Despite being a well-tolerated antidepressant, SSRIs have been associated with hyponatremia, a rare, but fatal adverse effect and the incidence ranges from 0.5%–32% in literature. Euvolemic hyponatremia is most commonly associated with syndrome of inappropriate secretion of antidiuretic hormone. An extensive review of literature was carried out, and we came across a total of 20 cases where escitalopram was reported as the causative agent of hyponatremia. We report a case of an 82-year-old female patient who had a history of acute onset, progressive memory impairment, and behavioral changes with depressive cognition precipitated by the death of her husband, for which she was treated with escitalopram 5 mg/day and clonazepam 0.5 mg/day. She was admitted to the hospital with presenting complaints of gait imbalance, tremors, irritability, confusion, decreased speech output and persecutory delusions. She was diagnosed with late-onset organic psychosis, precipitated and worsened by escitalopram-induced chronic uncontrolled euvolemic hyponatremia, with a sodium level of 115 mmol/L. On discontinuation of escitalopram, the patient’s serum sodium level improved gradually, and her consciousness became better. This is the second case with recurrent hyponatremia in the literature up to this date, with the other being reported by Tsai et al., in 2012. Furthermore, the dose of escitalopram was only 5 mg/day compared to other reported cases where the dose ranged between 10–20 mg/day.

Lung cancer complicated with syndrome of inappropriate secretion of antidiuretic hormone:A report of 2 cases and literature review / 吉林大学学报(医学版)

Objective:To analyze the clinical materials of 2 patients with lung cancer complicated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH),and to improve the clinical awareness and management.Methods:One patient was treated with lung cancer chemotherapy alone for 7 courses.The other patient received the strictly limited for liquid intake and tolvaptan by oral against hyponatremia without chemotherapy.Results:With the relapsing and advancing of lung cancer,the hyponatremia and its relevant symptoms of the first patient were poorly relieved.While the level of serum sodium of the second patient returned to the normal level 3 d after administration of tolvaptan.Conclusion:About one-third of the patients with hyponatremia have SIADH.The etiological treatment and symptomatic therapy of hyponatremia should be given to the patients in clinical treatment.

SIADH secundario a adenocarcinoma seroso de ovario tratado con tolvaptán / SIADH secondary to serous ovarian adenocarcinoma treated with tolvaptan

La hiponatremia es la alteración electrolítica más frecuente en el medio hospitalario, y en un 30% de los casos se debe a un síndrome de secreción inapropiada de vasopresina (SIADH). El SIADH está descrito como cuadro paraneoplásico endocrinológico en múltiples tumores, entre los que excepcionalmente se encuentra el de ovario y las neoplasias ginecológicas en general. Presentamos un caso de SIADH paraneoplásico por un citoadenocarcinoma seroso de ovario de alto grado, estadio IV. Se trata del primer caso de SIADH crónico por cáncer de ovario tratado con Tolvaptán. En el presente caso el objetivo de eunatremia se alcanzó con una dosis baja de acuarético, lo que apoya la elevada sensibilidad, ya previamente documentada, de los SIADH tumorales al tratamiento con Tolvaptán.

Hyponatremia is the most common electrolyte disturbance in hospitals, and 30% of cases are due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). SIADH is described as an endocrine paraneoplastic syndrome in multiple tumors including, ovary and gynecological malignancies in general, although these are exceptional. We report a case of paraneoplastic SIADH for high-grade serous ovarian cystoadenocarcinoma stage IV. This is the first case of chronic SIADH for ovarian cancer treated with Tolvaptan. In this case the target of eunatremia was reached with a low dose of aquaretic, which supports the high sensitivity, as previously documented, of paraneoplasic SIADH to Tolvaptan.

Case of Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Patient with Esophageal Cancer / 대한내과학회지

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may be observed in various types of cancer, but is mainly seen in small-cell carcinoma. It can also be caused by several chemotherapeutic agents. However, it is a very rare phenomenon in esophageal cancer or its treatment. We report here on a case of SIADH related to esophageal cancer treatment. A 55-year-old man received chemoradiotherapy (CRT) for esophageal cancer. After receiving CRT for 5 days, he complained of nausea, dizziness, and general weakness, and his sodium level had dropped to 107 mEq/L. His volume status was clinically euvolemic and there were no edema or pigmentation. After hypertonic saline infusion, the sodium level increased and the symptoms improved. There have been several reports of SIADH associated with malignancies or chemotherapy agents. However, to the best of our knowledge, this is the first Korean case of SIADH associated with esophageal cancer that occurred after cisplatin treatment.

Approach to the patients with adrenocortical insufficiency combined with the syndrome of inappropriate secretion of antidiuretic hormone / 中华内分泌代谢杂志

To summarize the clinical data of two cases with severe hyponatremia diagnosed as adrenal insuffiency combined with syndrome of inappropriate secret on of antidiuretic hormone(SIADH),and to review related literatures.Case 1 diagnosed as Addison's disease for 27 years and developed severe hyponatremia again but did not response well to sufficient glucocorticoid.Further examination showed SIADH caused by lung cancer and tolvaptan worked well.Case 2 was diagnosed as SIADH caused by lung cancer and responsed well to tolvaptan.However,hyponatremia reoccurred with the decreasing level of ACTH and cortisol during the chemotherapy.It was thought that hyponatremia was caused by drug-related adrenal insuffiency and glucocorticoid replacement therapy achieved good response.Both primary/secondary adrenal insuffiency and SIADH can lead to severe hyponatremia,but it is rare that the two situations exist in one patient and occur in different time.We should consider the possibility of the situations when we make differential diagnosis of refractory hyponatremia,monitoring the curative effects carefully,then correct the diagnosis timely,and reduce missed diagnosis and misdiagnosis.

Acute Hyponatremia in Pneumonia and CNS Infections of Children

PURPOSE: The option of selecting isotonic rather than hypotonic fluids for maintenance fluid in children has been advocated by some authors. Pneumonia and CNS infections are frequent clinical settings for acute hyponatremia because of nonosmotic anti-diuretic hormone stimuli in children. We conducted the present study to identify the incidence of hyponatremia in pneumonia and CNS infection of children and to determine the importance of maintenance intravenous fluid therapy regimen and other related factors. METHODS: The study included 1,992 patients admitted to the Department of Pediatrics at Pusan National University Children's Hospital between November 2008 and August 2011, who were diagnosed with pneumonia or CNS infections and checked for serum sodium concentration. Their clinical data including laboratory findings were reviewed retrospectively. RESULTS: During the study period, 218 patients were identified to have acute hyponatremia among 1,992 patients. The overall incidence of hyponatremia was 10.9%. The incidence of hyponatremia in encephalitis (37.3%) was highest and the incidence in bacterial meningitis (27.4%), viral meningitis (20.0%), bacterial pneumonia (11.1%), mycoplasma pneumonia (9.2%), and viral pneumonia (6.8%) were in descending order. The mean age was higher in hyponatremic patients than in isonatremic patients. The incidence of hyponatremia was higher in who had 0.18% NaCl in 5% dextrose (D5 0.18% NS) than 0.45% NaCl in 5% dextrose infusion (D5 1/2NS) (9.0% vs. 2.2%). SIADH was identified in 20.5% among hospital acquired hyponatremic patients after adequate evaluation for SIADH. CONCLUSION: We recommend D5 1/2NS rather than D5 0.18% NS as the maintenance fluid given to children with pneumonia or infectious CNS diseases.

Hyponatremia Induced Coma during Risperidone Treatment in 2 Cases of Schizophrenia / 대한정신약물학회지

Antipyschotics have been frequently reported being associated with hyponatremia. We have experienced two cases of severe hyponatremia with neurological symptoms in patients with acute schizophrenia who were treated with risperidone. Case 1 was a 33-year-old female who developed hyponatremia (Na+114 mEq/L) at 17 days after initiation of treatment with risperidone. Case 2 was a 41-year-old female who developed hyponatremia (Na+107 mEq/L) 5 months after treatment with risperidone. In both cases, polydipsia was not obvious. The exact cause of hyponatremia was uncertain, but we suggest that syndrome of inappropriate secretion of antidiuretic hormone due to risperidone may be the mechanism of hyponatremia in both cases. Although there have been many recent studies about the pathophysiology of hyponatremia among psychiatric patients, the exact mechanism remains unclear. There have been many case reports in the literature of hyponatremia associated with antipsychotics. We suggest that risperidone may be a potential drug that can cause hyponatremia and lead to life-threatening neurological symptoms in the early stage treatment, and that clinicians should monitor patients on a regular basis.

A case of syndrome of inappropriate secretion of antidiuretic hormone associated with paroxetine / 대한내과학회지

Paroxetine is a well-known selective serotonin reuptake inhibitor, and has been reported to be advantageous for chronic pain control. Paroxetine is increasingly used for various types of chronic pain because of its safety; however, hyponatremia, or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with paroxetine, has been reported. This complication is relatively rare, but some patients have presented with severe neurological symptoms. Here, we report the first case of SIADH associated with paroxetine in Korea.

Los antidepresivos inhibidores selectivos de recaptura de serotonina (ISRS, ISR-5HT) / Selective serotonin reuptake inhibitors antidepressants (SSRIs)

Depression is a frequent mental disorder in the general population. Approximately 3.7% of the population will suffer a major depressive episode throughout life. Pharmacological treatment with selective serotonin receptor inhibitors (SSRIs) is useful to treat this condition and other mental disorders. Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, which constitute this group, are characterized by having an easy way of administration and a very extensive security profile. Objectives The objectives in this revision were: 1. To establish current indications of selective serotonin receptor inhibitors, using as basis those authorized by the Food and Drug Administration (FDA) of the United States of America. 2. To describe the mechanisms that explain antidepressant action. Initially, the SSRIs inhibit the reuptake of serotonin at the synaptic cleft; later there is a downregulation of the 5HT1A receptors; and finally antidepressants raise the levels of brain derived neurotrophic factor (BDNF). 3. To present its way of administration and dosage. 4. To describe frequent collateral effects and those specifically associated to this group of antidepressants and the recommended treatment. Results SSRIs antidepressants are the first choice treatment in depression, in the anxiety disorder, the obsessive-compulsive disorder, the post-traumatic stress disorder, bulimia nervosa and the premenstrual dysphoric disorder. At present, SSRIs displace benzodiacepines in the treatment of generalized anxiety disorder, just as they displaced tricyclic antidepressants in the past. Depressed patients show less activity than normal of the serotonin neurotransmitter (serotonergic hypothesis of depression) and the reuptake blockade at the site of the serotonergic presinaptic receptors 5HT1A, 5HT2C and 5HT3C increases neurotransmission in this system. Desensitization of autoreceptors 5HT1A and the downregulation of the 5HT2 receptors coupled to the G protein, a late effect of the SSRIs, result in the improvement of the depressive symptoms. The mechanism that explains the relatively late antidepressant effect seems to be different to the acute and fast serotonergic effect responsible of improvement in the premenstrual dysphoric disorder. Moreover, these antidepressants, in the same way than mood stabilizers and electroconvulsive therapy, increase serum levels of the brain-derived neuronal growth factor, as well as other neurotrophic factors. Although the SSRIs dosages are variable, it is possible to start antidepressant treatment with therapeutic doses in the majority of cases; at the same time, if necessary, it is possible to augment them gradually up to the largest dose, with a wide security margin. Their most frequent collateral effects occur in the gastrointestinal system, in the sexual response and on bone density. Nevertheless, there are collateral effects specifically related to the use of these antidepressant medications: 1. The serotonergic syndrome, characterized by changes in the mental status, autonomic hyperactivity and neuromuscular anomalies. 2. The syndrome of inappropriate secretion of antidiuretic hormone, which occurs in 25% of the elder depressed patients treated, and which is characterized by a high serum osmolarity, low urinary osmolarity and hyponatremia. Its manifestations are malaise, myalgias, drowsiness and headache, but it may produce also confusion, convulsions and coma. 3. Gastrointestinal bleeding mainly and cutaneous bleeding: Use of SSRIs raises 2 to 4 times the risk of bleeding. When the patient takes aspirin it is raised up to 7 times, and with the concomitant use of anti-inflammatory drugs, by nearly 16 times. Other risk factors are age, the antecedent of bleeding and the potency of SSRIs to inhibit the serotonin reuptake. 4. The discontinuation syndrome, lesser with fluoxetine, and greater with paroxetine and sertraline. It appears by the second day and it lasts two weeks. Its manifestations are nausea, headache, paresthesias, nasal congestion and general malaise. They are due to the decrease in serotonin levels at the synaptic cleft. 6. Effects on the newborn when the SSRIs are used during pregnancy consist in specific congenital malformations. Sertraline has been associated to omphalocele, ventricular septum heart defects and anencephaly. Fluoxetine is associated to craniosynostosis and paroxetine to heart defects, gastroschisis, neural tube defects, omphalocele and anencephaly also. Its use also increases the range of spontaneous abortions up to 1.45 times, premature delivery and low birth weight, problems in the early newborn period (respiratory problems and hypotony), hypoglycemia, cyanosis, restlessness, convulsions and low Apgar. Its use during the third trimester can cause persistent lung hypertension. Although it is a rare condition, it is associated to a mortality range of 10% to 20%. 8) Little is known about the effects caused by the use of SSRIs during breastfeeding. In the case of sertraline and paroxetine, these antidepressant drugs are not detected in the child's serum; on the other hand, serum levels of citalopram were 1.9 nmol/L, fluoxetine 47 nmol/L, and venlafaxine 91 nmol/L. In the available studies, neither behavioral effects nor effects in the development of the newborn were observed. 9) Suicide risk or suicidality. Although the antidepressant treatment lowers both, ideation and the frequency of suicides in the patients treated, the FDA has established a series of general recommendations for the management of patients who start the treatment with antidepressants. To start with the lowest dose, to make an appointment weekly during six consecutive weeks, to recommend and facilitate contact via telephone, to prohibit the use of alcohol and drugs, to ask on each date about suicidal thoughts or behaviors or about self-mutilation, to document the information in the file and to use supportive psychotherapy or cognitive, behavioral or interpersonal therapies.

La depresión es un trastorno mental que afecta a 3.7 % de la población. Los antidepresivos inhibidores selectivos de la recaptura de serotonina (ISRS) resultan útiles en el tratamiento de éste y otros trastornos mentales. El citalopram, escitalopram, fluoxetina, fluvoxamina, paroxetina y sertralina constituyen este grupo de fácil administración y con un amplio perfil de seguridad. Objetivos 1) Establecer las indicaciones actuales de los antidepresivos ISRS. 2) Describir los mecanismos que explican su acción antidepresiva. 3) Describir los efectos secundarios frecuentes y aquéllos específicamente relacionados con este grupo antidepresivo. Resultados Los antidepresivos ISRS son el tratamiento de elección para la depresión, los trastornos de angustia, de ansiedad generalizada, obsesivo-compulsivo, de estrés postraumático, disfórico premenstrual y la bulimia nervosa. Los pacientes deprimidos muestran una actividad menor a la normal del neurotransmisor serotonina. La inhibición de la recaptura de la serotonina sobre los receptores serotoninérgicos presinápticos 5HT1A, 5HT2C y 5HT3C aumenta la neurotransmisión en este sistema. La desensibilización de los autorreceptores 5HT1A y la regulación hacia abajo (downregulation) de los receptores 5HT2 acoplados a la proteína G, efecto tardío de los ISRS, dan por resultado la mejoría de los síntomas depresivos. El mecanismo que explica el efecto antidepresivo relativamente tardío parece ser distinto al efecto serotoninérgico agudo y rápido responsable de la mejoría en el caso del trastorno disfórico premenstrual. Estos antidepresivos, como los estabilizadores del ánimo y la terapia electroconvulsiva, incrementan los niveles séricos del factor de crecimiento neuronal cerebral, así como de otros factores neurotróficos. Aunque las dosis de los ISRS son variables, en la mayoría de los casos es posible iniciar el tratamiento antidepresivo con dosis terapéuticas e incrementarlas paulatinamente hasta las dosis máximas con seguridad. Sus efectos secundarios más frecuentes son gastrointestinales, en la respuesta sexual y sobre la densidad ósea. Los efectos secundarios específicamente relacionados con el uso de estos antidepresivos son: 1. El síndrome serotoninérgico, caracterizado por cambios en el estado mental, hiperactividad autonómica y anomalías neuromusculares. 2. El síndrome de secreción inapropiada de hormona antidiurética, que se caracteriza por osmolaridad sérica alta, urinaria baja e hiponatremia, así como por mialgias, letargo, cefalea e incluso confusión, convulsiones y coma. 3. El sangrado, principalmente de tubo digestivo y cutáneo. El uso de los ISRS aumenta el riesgo de sangrar entre dos y cuatro veces. Cuando el paciente usa aspirina, el riesgo aumenta hasta siete veces y con el uso concomitante de antiinflamatorios, cerca de 16 veces. La edad, el antecedente de sangrado y la capacidad de inhibir la recaptura constituyen también factores de riesgo. 4. El síndrome de descontinuación, menor con la fluoxetina, mayor con la paroxetina y sertralina, aparece a partir del segundo día y su duración es de dos semanas. Manifestaciones como náusea, cefalea, parestesias, congestión nasal y malestar general se deben a la disminución de los niveles de serotonina en la sinapsis. 5. Los efectos sobre el producto cuando los ISRS se utilizan durante la gestación consisten en malformaciones congénitas específicas. La sertralina se ha asociado a onfalocele, defectos del septum cardíaco y anencefalia. A su vez, la fluoxetina se ha asociado a craneosinostosis y defectos cardíacos. Y la paroxetina a defectos cardíacos, gastrosquisis, defectos del tubo neural y también a onfalocele y anencefalia. Su uso también aumenta la tasa de abortos espontáneos hasta 1.45 veces, parto prematuro y bajo peso al nacer, problemas en el neonato inmediato (problemas respiratorios e hipotonía), hipoglucemia, cianosis, inquietud, convulsiones y Apgar bajo. Su uso durante el tercer trimestre puede ocasionar hipertensión pulmonar persistente que, aunque es rara, se asocia a una mortalidad de 10- 20 %. 6) De los efectos por el uso de ISRS durante la lactancia se conoce poco. En el caso de la sertralina y la paroxetina no se detectan estos antidepresivos en el suero del niño; en cambio, los niveles séricos de citalopram fueron de 1.9 nmol/L, de fluoxetina 47 nmol/L y de venlafaxina de 91 nmol/ L. En los estudios disponibles no se observaron efectos conductuales o en el desarrollo del recién nacido. 7) Suicidalidad o riego suicida. Aunque el tratamiento antidepresivo disminuye tanto la ideación y la frecuencia de suicidios en los pacientes tratados, la FDA ha establecido una serie de recomendaciones para el manejo de pacientes que inician el tratamiento con antidepresivos ISRS: Iniciar con la dosis más baja, citar semanalmente a los pacientes durante 6 semanas consecutivas, recomendar y facilitar el contacto telefónico, prohibir el uso de alcohol y drogas, interrogar en cada ocasión sobre pensamientos y comportamientos suicidas o autolesivos, documentar en el expediente la información y usar psicoterapia de apoyo, cognitivo-conductual o interpersonal en el tratamiento.

Cerebral salt wasting following pituitary surgery for macroadenoma / 대한내과학회지

The central nervous system (CNS) has important roles in the regulation of sodium and water homeostasis, so the risk of hyponatremia is increased for patients with neurological disorders. Cerebral salt wasting (CSW) is a syndrome that is characterized by hyponatremia and extracellular volume contraction, and these problems are caused by natriuresis and the concomitant polyuria in patient with intracranial disease. It is critical to differentiate CSW from syndrome of inappropriate secretion of antidiuretic hormone (SIADH) for patients with hyponatremia and after they experience cerebral insults. This is because fluid restriction is the treatment of choice for SIADH and administration of isotonic or hypertonic saline is important for treating CSW. We report here on a case of CSW following trassphenoidal surgery for pituitary tumor in a 67-year-old man with nonfunctioning pituitary macroadenoma. Hyposmotic hyponatremia, increased urine output and signs of dehydration developed postoperatively, and the patient was managed by water and salt supplementation.

Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Adjuvant Chemotherapy with Cisplatin plus Paclitaxel in Non-Small Cell Lung Cancer Patient / 결핵및호흡기질환

We report a case of pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following adjuvant chemotherapy. A 51-year-old woman with stage IIIA adenocarcinoma received left lower lobe lobectomy in July, 2006. And then combination chemotherapy with paclitaxel and cisplatin was given to the patient. In five days after completion of second cycle of the chemotherapy, she visited emergency room because of general weakness and seizure. Her brain MRI was shown to be no evidence of brain metastasis. Serum sodium, urine and plasma osmolarities were 117mEq/L, 589 and 244mOsm/kg, respectively. She was improved with fluid restriction. Although occurrence of SIADH following chemotherapy is rare, physician should give an attention the potential for development of SIADH in the course of chemotherapyin non-small cell lung cancer patient.

The Effect of Demeclocycline on the Management of Syndrome of Inappropriate Secretion of Antidiuretic Hormone in Brain Injured Patient

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a frequent complication of severe head trauma. Fluid restriction is treatment choice of SIADH in patients with traumatic brain injury (TBI), but fluid restriction is limited because they need sufficient calories. We described a patient who, on the four months after a head injury, presented with deterioration of consciousness, which coincided with the development of the SIADH, and which rapidly reversed with the correction of the hyponatremia by demeclocycline with minimal fluid restriction. We suggest that SIADH should be included in the differential diagnosis of deterioration of consciousness during the recovery period of the patients suffering from head injury because unexpected clinical deterioration may often have a reVersible cause. Also, demeclocycline will be useful, which allows for increased fluid liberalization and for provision of adequate calories, in the treatment of the SIADH in patients with TBI.

Cerebral Salt Wasting Syndrome Associated with Meningitis in a Child

Hyponatremia is commonly seen in those patients with central nervous system injury associated with infection or trauma. And decreasing intracranial pressure through restriction of maintenance fluid and salt is practiced as a routine therapeutic measure in the early stages of meningitis to prevent or ameliorate the syndrome of inappropriate secretion of antidiuretic hormone(SIADH). However, lots of patient do not show the typical symptoms of SIADH, instead they are dehydrated, have low plasma volume, increased urine sodium concentration and increased net sodium loss, which are the symptoms of cerebral salt wasting syndrome(CSW). Recent reports have prompted a reconsideration of CSW distinct from SIADH and moreover CSW has more proportion of hyponatremia associated with acute brain insult. CSW involves renal salt loss leading to hyponatremia and volume loss, whereas SIADH is a euvolemic or hypervolemic condition. While fluid restriction is the treatment of choice in SIADH, the treatment of CSW consists of vigorous sodium and volume replacement. And by correcting hyponatremic state as soon as possible, we can reduce mortality rate and improve neurologic sequelae. We report a case of CSW which was treated by replacement of vigorous sodium and volume replacement.

Transient Pancytopenia and SIADH associated with Administration of Carbamazepine

Carbamazepine is widely used to manage of seizures and symptomatic treatment of trigeminal neuralgia and central pain. We experienced two cases of exceedingly rare but potentially fatal side effects following carbamazepine administration. One traumatic brain injured patient developed pancytopenia 3 weeks after beginning to take carbamazepine for prophylactic management of seizure and the other C6 incomplete spinal cord injured patient receiving carbamazepine for the management of central pain sequentially developed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) 1 week after administration. Because of more frequent indications of carbamazepine, these side effects must be borne in mind and cautious administration will be desirable.