Síndrome de Fahr y síndrome poliglandular tipo 4 en un paciente con secreción inadecuada de hormona antidiurética

Mujer de 73 años con antecedente de epilepsia, deterioro cognitivo, rigidez y movimientos involuntarios. Ingresó por emergencia con cuadro de desorientación y dificultad del habla. La TEM cerebral mostró calcificaciones en los ganglios basales y hemisferios cerebelosos sugerentes de síndrome de Fahr. Se demostró un hipoparatiroidismo primario más enfermedad tiroidea autoinmune con una hiponatremia hipotónica euvolémica y sin alteración de otros ejes hipofisiarios. Se hizo el diagnóstico de síndrome poliglandular autoinmune tipo 4; además, el dosaje de ADH confirmó el diagnóstico de síndrome de secreción inadecuada de hormona antidiurética. Se administró calcio endovenoso, suplementos de vitamina D y calcitriol, con mejoría clínica neurológica importante.

Toxicidad ungueal asociada al tratamiento con urea / Nail toxicity associated with urea treatment

La melanoniquia es la pigmentación de la lámina ungueal, esta alteración es inducida por diversas causas: procesos inflamatorios, traumatismos, enfermedades autoinmunes o medicamentos. Existen numerosos fármacos que pueden producir alteraciones en las uñas (antiinfeciosos, antineoplásicos, retinoides), siendo reversibles en la mayoría de casos tras la suspensión del fármaco. La hidroxiurea es uno de los agentes quimioterápicos identificados como causante en raras ocasiones de toxicidad ungueal. Se trata de un derivado hidoxilado de la urea, que actúa inhibiendo la síntesis de ADN.En este artículo, presentamos el caso de una paciente trasplantada pulmonar de 61 años con diagnóstico de diabetes insípida que, sin embargo, durante su ingreso desarrolló un SIADH (secreción inadecuada de hormona antidiurética). El SIADH fue tratado con restricción hídrica y urea, tras el inicio de dicho tratamiento empezó a presentar lesiones en uñas de las manos y de los pies, que remitieron con el tiempo tras su retirada. Ningún otro fármaco de los prescritos durante su ingreso se ha relacionado con la toxicidad ungueal, por tanto se consideró la urea como posible causante de las lesiones ungueales en esta paciente. Esta reacción fue notificada al Sistema Español de Farmacovigilancia. (AU)

Melanonychia is the pigmentation of the nail, this alteration is induced by diverse causes: inflammatory processes, traumatisms, autoimmune diseases or medications. There are numerous drugs that can produce alterations in the nails (anti-infectious, chemotherapy agents, retinoid), the alterations are reversible in most cases after drug discontinuation. Chemotherapeutic agent hydroxyurea is identified as a cause of nail toxicity rarely. It is a hydroxylated derivative of urea, which acts by inhibiting DNA synthesis.In this article, we present the case of a 61-year-old lung transplant patient diagnosed with diabetes insipidus who, however, developed SIADH (inadequate secretion of antidiuretic hormone) during his hospitalization, the patient received treatment with water restriction and urea. After the start of treatment, the patient began to present lesions on the nails of the hands and feet, which remitted with time after drug discontinuation. No other medication prescribed during admission has been linked to nail toxicity, so urea was considered a possible cause of nail lesions in this patient. This reaction was notified to the Spanish Pharmacovigilance System. (AU)

Clinical experience with Tolvaptan outpatient use. Cost and effectiveness in 9 cases.

INTRODUCTION: Tolvaptan introduction has constituted the main therapeutic novelty in the management of hyponatremia in recent years. OBJECTIVE: To describe the experience with this drug at Complejo Asistencial Universitario de León, Spain. METHOD: Retrospective, observational study of tolvaptan outpatient use in a tertiary care hospital from March 2014 to August 2017. RESULTS: A total of 9 patients were treated with tolvaptan in the outpatient setting. Eunatremia was reached in 24 h by 23.1%. After tolvaptan administration, a reduction in days of hospitalization was recorded (361 vs. 70; p = 0.007), especially in those days of hospitalization that were attributable to hyponatremia (306 vs. 49; p = 0.009). CONCLUSIONS: Long-term use of tolvaptan appears to be safe and is associated with a decrease in days of hospitalization.

INTRODUCCIÓN: La introducción de tolvaptan ha supuesto la principal novedad en el tratamiento de la hiponatremia en los últimos años. OBJETIVO: Describir la experiencia con tolvaptan en el Complejo Asistencial Universitario de León, España. MÉTODO: Estudio observacional retrospectivo de utilización ambulatoria de tolvaptan en un hospital de tercer nivel, de marzo de 2014 a agosto de 2017. RESULTADOS: Fueron tratados con tolvaptan de forma ambulatoria nueve pacientes, 23.1 % alcanzó eunatremia en 24 horas. Posterior a la administración de tolvaptan se registró reducción en días de hospitalización (361 versus 70, p = 0.007), especialmente por hiponatremia (306 versus 49, p = 0.009). CONCLUSIONES: El uso a largo plazo de tolvaptan parece ser seguro y se relaciona con descenso en los días de hospitalización.

Experiencia clínica con el uso ambulatorio de tolvaptan. Costes y efectividad en nueve casos / Clinical experience with Tolvaptan outpatient use. Cost and effectiveness in 9 cases

Resumen Introducción: La introducción de tolvaptan ha supuesto la principal novedad en el tratamiento de la hiponatremia en los últimos años. Objetivo: Describir la experiencia con tolvaptan en el Complejo Asistencial Universitario de León, España. Método: Estudio observacional retrospectivo de utilización ambulatoria de tolvaptan en un hospital de tercer nivel, de marzo de 2014 a agosto de 2017. Resultados: Fueron tratados con tolvaptan de forma ambulatoria nueve pacientes, 23.1 % alcanzó eunatremia en 24 horas. Posterior a la administración de tolvaptan se registró reducción en días de hospitalización (361 versus 70, p = 0.007), especialmente por hiponatremia (306 versus 49, p = 0.009). Conclusiones: El uso a largo plazo de tolvaptan parece ser seguro y se relaciona con descenso en los días de hospitalización.

Abstract Introduction: Tolvaptan introduction has constituted the main therapeutic novelty in the management of hyponatremia in recent years. Objective: To describe the experience with this drug at Complejo Asistencial Universitario de León, Spain. Method: Retrospective, observational study of tolvaptan outpatient use in a tertiary care hospital from March 2014 to August 2017. Results: A total of 9 patients were treated with tolvaptan in the outpatient setting. Eunatremia was reached in 24 h by 23.1%. After tolvaptan administration, a reduction in days of hospitalization was recorded (361 vs. 70; p = 0.007), especially in those days of hospitalization that were attributable to hyponatremia (306 vs. 49; p = 0.009). Conclusions: Long-term use of tolvaptan appears to be safe and is associated with a decrease in days of hospitalization.

Carcinoma de próstata y síndrome de secreción inadecuada de hormona antidiurética / Prostate carcinoma and syndrome of inappropriate antidiuretic hormone secretio

El cáncer de próstata es una causa extremadamente rara de síndrome de secreción inadecuada de hormona antidiurética (SIADH). Se trata de tumores agresivos asociados a un síndrome que puede aparejar consecuencias graves. Un paciente de 64 años fue diagnosticado de adenocarcinoma de próstata Gleason 4+3: 7 en 2014 y recibió terapia de bloqueo hormonal. En 2015 debió ser ingresado por hiponatremia sintomática y se le diagnosticó un SIADH, sin otra causa probable más que el cáncer de próstata. Sufrió rápida progresión de su enfermedad oncológica, llamativamente cuando su PSA se encontraba en valores normales, y falleció al corto plazo. Existe gran variabilidad clínica e histopatológica de los casos informados en la literatura de asociación de carcinoma de próstata y SIADH, sin embargo, todos coinciden en la agresividad de estos tumores. Estas características se presentan en tumores con diferenciación neuroendocrina, frecuentemente resistentes al tratamiento hormonal y que pueden presentar síndromes paraneoplásicos como el SIADH. El perfil de sus alteraciones moleculares se encuentra en estudio para el desarrollo de terapias target. La asociación de adenocarcinoma de próstata y SIADH es muy infrecuente y podría implicar diferenciación neuroendocrina. Por tal motivo es esencial una nueva biopsia del tumor o de sus metástasis a la progresión de la enfermedad para poder conducir un tratamiento adecuado de acuerdo a sus características morfológicas, inmunohistoquímicas y, en un futuro, moleculares.

Prostate cancer is an extremely rare cause of syndrome of inappropriate antidiuretic hormone (SIADH) secretion. These tend to be aggressive tumors and SIADH can carry serious clinical consequences. A 64 years old patient was diagnosed with Gleason 4+3: 7 prostate adenocarcinoma in December 2014 and received hormonal blockade therapy. By March 2015 he was admitted for symptomatic hyponatremia and SIADH secretion was diagnosed, with no other probable cause than prostate cancer. He suffered a rapid progression of his oncologic disease, surprisingly with PSA in normal range, and died in the short term. There is great clinical and histopathological variability in the cases reported in the literature of association of prostate carcinoma and SIADH. However, they all agree on the aggressiveness of these tumors. This characteristic is present in tumors that have neuroendocrine features. They are frequently resistant to hormonal treatment and may present with paraneoplastic syndromes such as SIADH. The profile of its molecular alterations is under study for the development of target therapies. The association of prostate adenocarcinoma and SIADH is very uncommon and could involve neuroendocrine differentiation. For this reason, it is essential to perform a new biopsy of the tumor or its metastases at the progressive disease in order to conduct an appropriate treatment according to its morphological, immunohistochemical and, in the future, molecular characteristics.

[Association between moderate-severe bronchiolitis and syndrome of inappropriate antidiuretic hormone secretion in emergency departments]. / Asociación entre bronquiolitis moderada-grave y síndrome de secreción inadecuada de hormona antidiurética en urgencias.

OBJECTIVES: To identify clinical characteristics that may lead to the early recognition of patients admitted to the hospital for moderate-to-severe bronchiolitis with urine results associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). PATIENTS AND METHODS: A prospective observational study was conducted, spanning the bronchiolitis epidemic season (October 2012-March 2013), including all children who were admitted to the hospital with a diagnosis of moderate-to-severe bronchiolitis. The following criteria were used to establish a diagnosis of SIADH: urine sodium level of 40 mmol/L or greater, urine osmolarity above 500 mosm/Kg, and urine density of 1020 g/L or greater. Demographic characteristics, ventilation mode and clinical outcome were also analyzed. A comparison was made between those patients that met urine SIADH criteria and those who did not. RESULTS: A total of 126 children were included, and 23 (18.6%) of them had urine SIADH criteria. Patients in this group had a higher incidence of pneumonia and/or atelectasis on chest X-Ray (21.7% vs. 1.9%, P=.002), worse response to bronchodilator treatment with nebulized adrenaline (69,5% vs. 28,1%, P=.016), more need for respiratory assistance (high flow oxygen therapy (17.4% vs. 7.7%, p=.016), or non-invasive mechanical ventilation (13% vs. 5.8%, P=.034), and more admissions to the PICU (26.1% vs. 6.8%, P=.007). CONCLUSIONS: Patients older than one month with acute moderate bronchiolitis and urine SIADH criteria have worse clinical courses and more need for non-invasive mechanical ventilation, PICU admission, and have a higher incidence of pneumonia on chest X-ray. For that reason, it is recommended to collect a urine sample from these patients to allow an early diagnosis of SIADH, and thus early treatment of fluid and electrolyte abnormalities.

Abdominal pain and syndrome of inappropriate antidiuretic hormone secretion as clinical presentation of acute intermittent porphyria. / Dolor abdominal y síndrome de secreción inadecuada de hormona antidiurética, forma de presentación de porfiria aguda intermitente.

Acute intermittent porphyria (AIP) is a rare condition characterized by abdominal pain and a wide range of nonspecific symptoms. We report the case of a woman with abdominal pain and syndrome of inappropriate antidiuretic hormone secretion (SIADH) as clinical presentation of AIP. The diagnosis was achieved through the etiologic study of the SIADH.

Hiponatremia severa e hidrocefalia normotensiva del adulto: Reporte de un caso / Severe hyponatremia and normotensive hydrocephalus in the adult: Report of a case

Presentamos una paciente de 62 años de edad que ingresa por cefalea, alteraciones conductuales, síndrome tónico-frontal simétrico y síndrome cerebeloso de dos meses de evolución asociado a hiponatremia crónica severa. Se plantea el diagnóstico de síndrome de secreción inadecuada de hormona antidiurética (ADH) secundario a hidrocefalia normotensiva del adulto, presentando clara mejoría con la derivación ventrículo-peritoneal. Este caso pretende aportar información sobre una asociación descrita pero poco frecuente.

We present a 62-year-old patient presenting with a two-month episode of headaches, disrupted behavior, symmetric tonic frontal syndrome and cerebellar syndrome associated with severe chronic hyponaetremia. The diagnosis upon admission was an inadequate anti-diuretic hormone (ADH) secretion syndrome secondary to normotensive hydrocephalus of the adult, clearly improving after the ventricular-peritoneal shunt. This case provides information on a rarely reported association.

Hyponatremia in the neurocritical care patient: An approach based on current evidence.

In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of "cerebral salt wasting", which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution.

Syndrome of inappropriate antidiuretic hormone secretion related to Guillain-Barré syndrome after laparoscopic cholecystectomy / Síndrome da secreção inapropriada do hormônio antidiurético relacionada à síndrome de Guillain-Barré após colecistectomia videolaparoscópica / Síndrome de secreción inapropiada de hormona antidiurética relacionado con el síndrome de Guillain-Barré tras colecistectomía laparoscópica

Background and objectives: Guillain-Barré Syndrome is one of the most common causes of acute polyneuropathy in adults. Recently, the occurrence of Guillain-Barré Syndrome after major and minor surgical operations has been increasingly debated. In Guillain-Barré syndrome, syndrome of inappropriate antidiuretic hormone secretion and dysautonomy are generally observed after maximal motor deficit. Case report: A 44-year-old male patient underwent a laparoscopic cholecystectomy for acute cholecystitis. After the development of a severe headache, nausea, diplopia, and attacks of hypertension in the early postoperative period, a computer tomography of the brain was normal. Laboratory tests revealed hyponatremia linked to syndrome of inappropriate antidiuretic hormone secretion, the patient's fluids were restricted, and furosemide and 3% NaCl treatment was initiated. On the second day postoperative, the patient developed numbness moving upward from the hands and feet, loss of strength, difficulty swallowing and respiratory distress. Guillain-Barré syndrome was suspected, and the patient was moved to intensive care. Cerebrospinal fluid examination showed 320 mg/dL protein, and acute motor-sensorial axonal neuropathy was identified by electromyelography. Guillain-Barré syndrome was diagnosed, and intravenous immune globulin treatment (0.4 g/kg/day, 5 days) was initiated. After 10 days in the intensive care unit, at which the respiratory, hemodynamic, neurologic and laboratory results returned to normal, the patient was transferred to the neurology service. Conclusions: Our case report indicates that although syndrome of inappropriate antidiuretic hormone secretion and autonomic dysfunction are rarely the initial characteristics of Guillain-Barré syndrome, the possibility of postoperative syndrome of inappropriate antidiuretic hormone secretion should be kept in mind. The presence of secondary hyponatremia ...

Justificativa e objetivos: a síndrome de Guillain-Barré é uma das causas mais comuns de polineuropatia aguda em adultos. Recentemente, a ocorrência após grandes e pequenas intervenções cirúrgicas tem sido cada vez mais debatida. Na Guillain-Barré, a síndrome da secreção inapropriada do hormônio antidiurético e a disautonomia são geralmente observadas após déficit motor máximo. Relato de caso: paciente do sexo masculino, 44 anos, submetido a colecistectomia videolaparoscópica para colecistite aguda. Após desenvolver uma forte dor de cabeça, náusea, diplopia e ataques de hipertensão no período pós-operatório imediato, uma tomografia computadorizada do cérebro revelou-se normal. Os exames laboratoriais revelaram hiponatremia associada à síndrome de secreção inadequada de hormônio antidiurético; os líquidos foram restritos e tratamento com furosemida e NaCl a 3% foi iniciado. No segundo dia pós-operatório, o paciente desenvolveu dormência que se propagava a partir das mãos e dos pés, perda de força, dificuldade para engolir e respirar. Suspeitou-se de síndrome de Guillain-Barré e o paciente foi transferido para a unidade de tratamento intensivo. Exame do líquido cefalorraquidiano revelou 320 mg/dL de proteína e neuropatia axonal sensório-motora aguda foi identificada por eletromiografia. Síndrome de Guillain-Barré foi diagnosticada e tratamento intravenoso com imunoglobuliva (0,4 g/kg/dia, cinco dias) foi iniciado. Após 10 dias na unidade de terapia intensiva, durante os quais os parâmetros respiratório, hemodinâmico, neurológicos e laboratoriais voltaram ao normal, o paciente foi transferido para o serviço de neurologia. Conclusões: nosso relato de caso indica que, ...

Justificación y objetivos: el síndrome de Guillain-Barré es una de las causas más comunes de polineuropatía aguda en adultos. Recientemente, la aparición del síndrome de Guillain-Barré después de cirugías mayores o menores se ha convertido en objeto de debate cada vez mayor. En el síndrome de Guillain-Barré, generalmente se observan síndrome de secreción inapropiada de hormona antidiurética y disautonomía después de un déficit motor máximo. Relato de caso: paciente de sexo masculino, 44 años, sometido a colecistectomía laparoscópica por colecistitis aguda. Después de comenzar con un fuerte dolor de cabeza, náuseas, diplopía y ataques de hipertensión en el período postoperatorio inmediato, una tomografía computadorizada del cerebro del paciente se reveló normal. Las pruebas de laboratorio revelaron hiponatremia asociada con el síndrome de secreción inadecuada de hormona antidiurética; los líquidos se restringieron y se inició tratamiento con furosemida y NaCl al 3%. En el segundo día del postoperatorio, el paciente presentó adormecimiento que se propagaba desde las manos y los pies, pérdida de fuerza, dificultad para tragar y para respirar. Se sospechó síndrome de Guillain-Barré y el paciente fue derivado a la unidad de cuidados intensivos. El examen del líquido cefalorraquídeo reveló 320 mg/dL de proteína y mediante electromiografía se identificó neuropatía axonal sensorial y motora aguda. Se diagnosticó síndrome de Guillain-Barré y se inició el tratamiento intravenoso con inmunoglobulina (0,4 g/kg/día, durante 5 días). Después de 10 días en la unidad de cuidados intensivos, durante los cuales los parámetros respiratorio, hemodinámico, neurológico ...

Clinical guidelines for management of diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion after pituitary surgery.

Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring.

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.