Pharmacokinetics of Trazodone in Hispaniolan Parrots (Amazona ventralis).

The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.

The Tissue-Specific Eco-Exposome: Differential Pharmaceutical Bioaccumulation and Disposition in Fish among Trophic Positions.

Though bioaccumulation of pharmaceuticals by aquatic organisms continues to receive scientific attention, the internal disposition of these contaminants among different tissue compartments of fish species has been infrequently investigated, particularly among fish at different trophic positions. We tested a human to fish biological read-across hypothesis for contaminant disposition by examining tissue-specific accumulation in three understudied species, longnose gar (Lepisosteus osseus; piscivore), gizzard shad (Dorosoma cepedianum; planktivore/detritivore), and smallmouth buffalo (Ictiobus bubalus; benthivore), from a river influenced by municipal effluent discharge. In addition to surface water, fish plasma, and brain, gill, gonad, liver, and lateral muscle fillet tissues were analyzed via isotope dilution liquid chromatography tandem mass spectrometry. Caffeine and sucralose, two common effluent tracers, were quantitated at low micrograms per liter levels in surface water, while an anticonvulsant, carbamazepine, was observed at levels up to 37 ng/L. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and primary metabolites were detected in at least one tissue of all three species at low micrograms per kilogram concentrations. Within each species, brain and liver of select fish contained the highest levels of SSRIs compared to plasma and other tissues, which is generally consistent with human tissue disposition patterns. However, we observed differential accumulation among specific tissue types and species. For example, mean levels of sertraline in brain and liver tissues were 13.4 µg/kg and 1.5 µg/kg in gizzard shad and 1.3 µg/kg and 7.3 µg/kg in longnose gar, respectively. In contrast, smallmouth buffalo did not consistently accumulate SSRIs to detectable levels. Tissue-specific eco-exposome efforts are necessary to understand mechanisms associated with such marked bioaccumulation and internal dispositional differences among freshwater fish species occupying different trophic positions. Environ Toxicol Chem 2024;43:1894-1902. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine.

Fenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child-Pugh A/B/C, respectively) and healthy control subjects (n = 22) matched for sex, age, and BMI. All subjects underwent serial sampling to determine total plasma concentrations of fenfluramine and its active metabolite, norfenfluramine. Hepatic impairment was associated with increases in fenfluramine exposures, mainly area-under-the-curve (AUC). Geometric least squares mean ratios (90% confidence intervals) for fenfluramine AUC0-∞ in mild, moderate, and severe HI versus healthy controls were 1.98 (1.36-2.90), 2.13 (1.43-3.17), and 2.77 (1.82-4.24), respectively. Changes in exposure to norfenfluramine in mild, moderate, and severe HI were minimal compared with normal hepatic function. Exposures to fenfluramine and norfenfluramine in all HI groups were within the ranges that have been characterized in the overall development program, including ranges examined in exposure-response relationships for efficacy and safety in patients, and determined to have an acceptable safety profile. Mild and moderate HI had a modest effect on fenfluramine exposure that was not clinically meaningful, whereas the higher fenfluramine exposure in severe HI may require dose reduction based on general caution in this population. The modest decrease in norfenfluramine exposure is not considered clinically relevant.

¿Son útiles los antidepresivos para el dolor abdominal funcional? / Are antidepressants useful for functional abdominal pain?

Conclusiones de los autores del estudio: los antidepresivos fueron eficaces para el tratamiento del dolor abdominal funcional, siendo mayor la respuesta a los inhibidores de la recaptación de serotonina que a los antidepresivos tricíclicos, independientemente del componente psiquiátrico asociado. Se valoran poco los síntomas gastrointestinales provocados por el fármaco, frecuente causa de la retirada de la medicación. Comentario de los revisores: los antidepresivos parecen ser eficaces para el tratamiento del dolor abdominal funcional, con una ventaja terapéutica de los inhibidores de la recaptación de serotonina frente a los tricíclicos. Sin embargo, dadas las limitaciones metodológicas del trabajo, la falta de concordancia con otros datos disponibles y el porcentaje alto de efectos adversos, parece prudente esperar a la realización de estudios más amplios y de mayor calidad para poder recomendar su uso en esta patología funcional

Authors' conclusions: patients had more response to serotonin reuptake inhibitors than to tricyclic antidepressants, independently of the associated psychiatric component. They give little importance to the gastrointestinal symptoms caused by the drug that could be the cause of the withdrawal of the medication. Reviewers' commentary: antidepressants appear to be effective for the treatment of functional abdominal pain, with a therapeutic advantage of serotonin reuptake inhibitors over tricyclics. However, given the methodological limitations of the study, the lack of concordance with other available data and the high percentage of adverse effects, it seems prudent to wait for larger and higher quality studies to be able to recommend its use in this functional pathology

Eficacia de lamotrigina en un caso de trastorno de despersonalización resistente / The efficacy of lamotrigine in a resistant case of depersonalization disorder

Cuando sufre despersonalización, el individuo se queja espontáneamente de la vivencia de que su propia actividad mental, su cuerpo, su entorno o todos ellos, están cualitativamente transformados, de manera que se han vuelto irreales, lejanos o mecánicos. Este fenómeno está asociado frecuentemente con otros trastornos mentales, como en el caso que presentamos. Entre los muchos fármacos estudiados, ninguno ha mostrado ser el tratamiento de elección. Entre aquellos que han obtenido mejores resultados están los antagonistas de los receptores de los opioides, la combinación de inhibidores selectivos de la recaptación de la serotonina con lamotrigina, y la clorimipramina. Presentamos un caso resistente que respondió a lamotrigina (AU)

The individuals with depersonalizattion disorder suffer from a painful feeling that their body and mental experiences or the experiences of the environment seem become unreal, distant or mechanical. This phenomenon is often associated with other mental disorders, as in the case presented. Among the many psychoactive drugs studied, none of them has been shown to be the treatment of choice. Among those with which the best results are obtained are opioid receptor antagonists, the combination of selective serotonin reuptake inhibitors with lamotrigine and clorimipramine. We are presenting a resistant case that responded to lamotrigine(AU)

La hipersexualidad: nuevos aportes a su conceptualización y tratamiento / Hypersexuality: new contributions to the conceptualization and treatment

Objetivo: este artículo revisa el concepto de hipersexualidad, las condiciones asociadas a dicho comportamiento así como los tratamientos indicados para el mismo.Métodos: llevamos a cabo una búsqueda en internet de artículos en lenguaje inglés publicados en los últimos 20 años (hipersexualidad, sexualidad humana, comportamiento hipersexual, ninfomanía).Resultados: la hipersexualidad es un cambio en las formas e incremento en la frecuencia de los comportamientos sexuales. La etiología de la hipersexualidad es compleja e involucra una variedad de mecanismos fisiológicos y psicológicos. Puede ser idiopática o el resultado final de muchos procesos de enfermedad subyacentes. La disfunción del lóbulo frontal y de otras áreas cerebrales puede conducir a la desinhibición en el comportamiento sexual y a hipersexualidad; esta condición también puede ser el resultado de otros trastornos neurológicos, psiquiátricos o efectos secundarios de medicamentos. Cuando la causa subyacente puede ser tratada, el comportamiento sexual desinhibido cesa. Conclusión: la hipersexualidad puede ocasionar conductas de difícil manejo, pero los métodos farmacológicos pueden controlar de manera exitosa estos comportamientos en la mayoría de los pacientes.

Objective: This article reviews the concept of hypersexuality, the conditions attached to such behavior and the treatments prescribed for it. Methods: We conducted an internet search for English-language articles published over the past 20 years (Hypersexuality, human sexuality, hypersexual behavior, Nymphomania). Results: Hypersexuality is a change in the ways and an increase in the frequency of the sexual behaviors. The etiology of hypersexuality is complex and involves a variety of physiological and psychological mechanisms. It may be idiopathic or the final result of many underling disease processes. The dysfunction of the frontal lobe and other brain areas can lead to the disinhibition in the sexual behavior and hypersexuality; this condition can also be the result of other neurological and psychiatric disorders or an adverse effect of medications. When the underlying cause can be treated, the uninhibited sexual behavior ceases. Conclusion: Hypersexuality can cause unmanageable behavior, but pharmacological methods can successfully control this behavior in most patients.

Inhibición de la recaptación de serotonina en procesos inflamatorios / No disponible

No disponible

Tratamiento farmacológico de la fibromialgia: hacia la neuromodulación química / Pharmacologic treatment of fibromyalgia: towards chemical neuromodulation

La fibromialgia (FM) es una patología crónica, cuyo síntoma principal es el dolor, el cual no responde a los analgésicos tradicionales. Las características clínicas y los diferentes hallazgos neurofisiológicos en estos pacientes apuntan a un proceso de sensibilización central del sistema nociceptivo como eje fisiopatológico central en esta enfermedad. El conocimiento del funcionamiento del sistema nociceptivo y de su comportamiento en esta enfermedad nos ha aportado en los últimos años nuevas posibilidades en el abordaje terapéutico. Así, están siendo desarrollados fármacos con un mecanismo de acción diferencial, que pueden ejercer una modulación de la actividad del sistema nociceptivo capaz de producir analgesia donde otros fármacos han fracasado. Diferentes fármacos con capacidad de incrementar la actividad de las bioaminas implicadas en los procesos de inhibición nociceptiva y otros dirigidos a ejercer una disminución de la excitabilidad del sistema, a través de los canales iónicos, están siendo probados con beneficio en los pacientes con FM y pueden conformar un perfil farmacológico neuromodulador más racional en esta enfermedad. En este artículo se revisan las diferentes estrategias farmacológicas con evidencia científica y se apuntan algunas líneas de futuro que fortalezcan el cambio terapéutico que se está produciendo en el abordaje farmacológico de estos pacientes (AU)

Fibromyalgia is a chronic pathology and its main symptom is pain which usually does not respond to traditional analgesia. Its clinical characteristics and the diverse neurophysiologic findings in these patients point to a central sensitization process of the nociceptive system as the central physiopathologic axis in this disease. The knowledge of the nociceptive system functioning and its behavior in this disease has led, in the past few years, to new possibilities for the therapeutic approach. In that way, drugs with a differential mechanism of action, allowing a modulation of the nociceptive system capable of producing analgesia where other medications have failed are being developed. Different drugs with the capacity increasing the activity of biologically active amines implicated in the nociceptive inhibition process and others which are destined to reduce the excitability of the system through ion channels, are being tested with some benefit in Fibromyalgia patients and may constitute a more rational neuromodulating drug profile for this disease. This article reviews the different pharmacological strategies supported by scientific evidence and points to some future research lines that fortifies the therapeutic change taking place in the treatment approach of these patients (AU)

Bioequivalência de duas formulações de oxalato de escitalopram comprimidos em voluntários sadios administradas em jejum / Bioequivalence of two tablets formulations of escitalopram oxalate in healthy volunteers under fasting conditions

O estudo foi conduzido para verificar a bioequivalência entre duas formulações de oxalato de escitalopram 10 mg, comprimidos. Foram 32 voluntários sadios de ambos os sexos que participaram no estudo randomizado, cruzado, dois períodos, com washout mínimo de dez dias. Um comprimido de cada formulação foi administrado após jejum noturno de dez horas. Após administração, amostras seriadas de sangue foram coletadas por 144 horas. As amostras de plasma foram analisadas para determinação do escitalopram por método validado de cromatografia líquida acoplada à detecção por espectrometria de massas (LC-MS-MS). Os parâmetros farmacocinéticos área sob a curva de concentração plasmática do tempo zero a última concentração medida (ASC0-t) e concentração máxima observada (Cmax) foram os principais critérios para verificação da bioequivalência entre as formulações. Área sob a curva de zero a infinito (ASC0-inf), tempo em que ocorre Cmax (Tmax) e meia-vida (t1/2) também foram determinados. Os intervalos de confiança (IC) de 90% obtidos por análise de variância (ANOVA) não mostraram diferenças significativas entre as duas formulações e caíram dentro dos limites pre-estabelecidos (96,91-106,79 para ASC0-t e 89,40-102,39 para Cmax). A bioequivalência entre as duas formulações foi demonstrada tanto em termos de taxa quanto de extensão da absorção.

Interacciones medicamentosas de darunavir / Pharmacological interactions with darunavir

Darunavir es un nuevo inhibidor de la proteasa del virus dela inmunodeficiencia humana (VIH) que ha demostradotener una gran utilidad en el tratamiento de los pacientesinfectados por el VIH. Darunavir se metaboliza por elcitocromo P450 hepático, por lo que su administración condosis bajas de ritonavir resulta en un marcado incrementoen la exposición a éste y permite reducir el número decomprimidos y de dosis diarias. Tanto darunavir comoritonavir actúan como inhibidores a la vez que sustratosdel citocromo CYP3A4, por lo que son susceptibles depresentar interacciones medicamentosas con un amplionúmero de fármacos comúnmente usados en los pacientesinfectados por el VIH. El objetivo de esta revisión es el deresumir los principales estudios llevados a cabo paraevaluar dichas interacciones y servir de guía para elmanejo del tratamiento con darunavir/ritonavir en lapráctica clínica(AU)

Darunavir is a new HIV protease inhibitor that has beenshown to be highly useful in HIV-infected patients. Thisdrug is primarily metabolized by the liver through thecytochrome P450 3A4 (CYP3A4) isozyme and consequentlycoadministration with low doses of ritonavir markedlyincreases exposure and allows both daily doses and pillburden to be reduced. Both darunavir and ritonavir act asinhibitors and substrates of CYP3A4 and may thereforepresent pharmacological interactions with a large numberof drugs commonly used in HIV-infected patients. Thepresent review aims to summarize the main studies thathave evaluated drug interactions and to providerecommendations on treatment with darunavir/ritonavir inclinical practice(AU)

Impacto estratégico de la Medicina individualizada. Implicaciones en la clínica de la farmacogenética / No disponible

No disponible

Efectos de citalopram, reboxetina y nefazondona sobre diversas preparaciones de órgano aislado de cobaya y de rata "in vitro" / Effectos of citalopram, reboxetine and nefazodone in differentes tissues form guinea-pig and rat "in vitro"

El citalopram, la reboxetina y la nefazodona son fármacos antidepresivos que fundamentalmente inhiben la recaptación neuronal de serotonina, aunque se han descrito otras interacciones. Se estudian los efectos de citalopram, reboxetina y nefazodona sobre noradrenalina (NA), dopamina (DA) o potasio (K+) en conducto deferente de rata; histamina (H), acetilcolina (Ach), 4-aminopiridina (4-AP) y potasio en ileon aislado de cobaya y serotonina (5-HT), oxitocina y potasio en útero aislado de rata. Se utilizó solución de Krebs-Henseleit con o sin adición de cocaína, 17-beta estradiol y propranolol, para el conducto deferente aislado de rata, solución de Jalón para el útero de rata y solución de Tyrode para el ileon aislado de cobaya. Cuando fue posible se calcularon los valores de pD'2. CONCLUSIONES: El citalopram inhibe las contracciones inducidas por Ach (pD'2 = 4.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.4 ± 0.4) y potasio (pD'2 = 4.3 ± 0.3) en ileon aislado de cobaya; 5-HT (pD'2 = 3.5 ± 0.3), oxitocina (pD'2= 4.8 ± 0.3) y potasio (pD'2= 4.2 ± 0.3) en útero de rata. La reboxetina inhibe las contracciones inducidas por 5-HT (pD'2= 5.1 ± 0.4), oxitocina (pD'2= 4.9 ± 0.3) y potasio (pD'2= 5.1 ± 0.4) en útero de rata y DA (pD'2= 4.6 ± 0.4 en conducto deferente aislado de rata. La nefazodona inhibe las contracciones inducidas por Ach (pD'2= 5.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.2 ± 0.3) y potasio (pD'2 = 5.2 ± 0.4) en ileon aislado de cobaya; 5-HT (pD'2 = 7.0 ± 0.5), oxitocina (pD'2 = 5.2 ± 0.4) y potasio (pD'2 = 5.2 ± 0.4) en útero de rata; NA (pD'2 = 2.4 ± 0.1), DA (pD'2 = 5.2 ± 0.4) y potasio (pD'2 = 4.4 ± 0.4) en conducto deferente aislado de rata. Otras interacciones no son estadísticamente significativas (AU)

Citalopram, reboxetine and nefazodone are antidepressants which mainly inhibit serotonin (5-HT) reuptake, other interactions have been described. Therefore, the effects of citalopram, reboxetine and nefazodone on noradrenaline (NA), dopamine (DA), or K+ - contracted rat vas deferens have studied. The effects on 5-HT, oxytocin and K+-induced contractions in rat uterus and those on histamine (H), acetylcholine (Ach), 4-aminopyridine (4-AP) and K+-contractions in guinea-pig ileum were also studied. Krebs-Henseleit solution with and without adding cocaine, 17 beta estradiol and propranolol was used for rat vas deferens tissues. Jalon solution for rat uterus and Tyrode solution for guinea-pig ileum. When possible pD'2 values were calculated. CONCLUSIONS: Citalopram inhibited contractions induced by Ach (pD'2 = 4.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.4 ± 0.4), and potassium (pD'2 = 4.3 ± 0.3) in guinea-pig ileum; 5-HT (pD'2 = 3.5 ± 0.3), oxytocin (pD'2 = 4.8 ± 0.3) and potassium (pD'2 = 4.2 ± 0.3) in rat uterus. Reboxetine inhibited contractions induced by 5-HT (pD'2 = 5.1 ± 0.4), oxytocin (pD'2 = 4.9 ± 0.3) and potassium (pD'2 = 5.1 ± 0.4) in rat uterus; DA (pD'2 = 4.6 ± 0.4) in rat vas deferens. Nefazodone inhibited contractions induced by Ach (pD'2 = 5.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.2 ± 0.3) and potassium (pD'2 = 5.2 ± 0.4) in guinea-pig ileum; 5-HT (pD'2 = 7.0 ± 0.5), oxytocin (pD'2 = 5.2 ± 0.4), and potassium (pD'2 = 5.2 ± 0.4) in rat uterus; NA pD'2 = 2.4 ± 0.1), DA (pD'2 = 5.2 ± 0.4) and potassium (pD'2 = 4.4 ± 0.4) in rat vas deferens. Other interactions were not statistically significant (AU)

Efectos secundarios de los ISRS sin importancia para la salud que pueden contribuir al mal cumplimiento o al abandono del tratamiento / Non-serious adverse effects of selective serotonin uptake inhibitors that may contribute to poor treatment adherence or withdrawal

Introducción: Los inhibidores selectivos de la recaptación de serotonina (ISRS) son los fármacos más usados en los trastornos depresivos por su menor toxicidad, fácil dosificación y un supuesto mejor perfil de tolerabilidad. El correcto cumplimiento del tratamiento farmacológico es aún un reto importante que condiciona la probabilidad de recaída y el resultado terapéutico. Efectos secundarios sin gravedad, incluso sin ninguna trascendencia para la salud de las personas, pueden tener un peso importante a la hora de que éstas decidan abandonar el tratamiento. El objetivo principal de este estudio es valorar la frecuencia con que aparecen determinados efectos secundarios derivados del uso de los ISRS, de características leves, pero que pueden afectar a la calidad de vida de los pacientes y contribuir al abandono del tratamiento. Métodos: Estudio descriptivo, observacional y transversal, con una muestra de 116 pacientes ambulatorios que estaban en tratamiento con ISRS. Resultados: El 75% eran mujeres, con una media de edad de 47,59 años. El principio activo más prescrito fue paroxetina (25,4%). El 81% de los pacientes presentaron efectos adversos, los cuales se produjeron, en mayor o menor grado, con todos los ISRS. El fármaco mejor tolerado fue escitalopram, seguido por sertralina y citalopram, mientras que paroxetina y fluoxetina fueron los peor tolerados, según las variables analizadas en el estudio. Conclusiones: Este estudio pone de manifiesto que hay un grupo de efectos secundarios banales pero molestos producidos por los ISRS de los que hay poco publicado, pero que pueden contribuir al mal cumplimiento terapéutico (AU)

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most widely used drugs in depressive disorders, due to their lower toxicity, easy dosage, and supposedly better tolerability profile. Proper compliance and adherence to drug treatment remains a challenge that affects the probability of relapse and therapeutic outcomes. Non-serious adverse effects, even those with no significance for the patient's health, can be a determining factor in non-compliance. The main objective of this study was to assess the frequency of certain mild adverse effects associated with SSRIs that may affect patients' quality of life and contribute to treatment withdrawal. Method: We performed a descriptive, observational and cross-sectional study in a sample of 116 outpatients treated with SSRIs. Results: Seventy-five percent of the patients were women. The mean age was 47.59 years. The most frequently prescribed drug was paroxetine (25.4%). Adverse events were found in 81% of the patients and, to a greater or lesser degree, occurred with all SSRIs. The best tolerated drug was escitalopram, followed by sertraline and citalopram, while the worst tolerated drugs were fluoxetine and paroxetine according to the variables analyzed in this study. Conclusions: This study reveals the existence of a group of trivial but annoying side effects caused by SSRIs. Little has been published in the literature on these effects, which may contribute to poor treatment adherence (AU)

Agomelatina: un nuevo enfoque farmacológico en el tratamiento de la depresión con traducción clínica / No disponible

No disponible

Mejoría del dolor articular en un cuadro depresivo concomitante tratado con duloxetina / Improvement in joint pain in concomitant depression treated with duloxetine

Los pacientes con trastornos depresivos frecuentemente manifiestan quejas somáticas como, por ejemplo, dolor. La mejoría en la percepción del dolor que se produce en pacientes con síntomas depresivos tratados con antidepresivos puede deberse a una mejoría en la depresión. Varias publicaciones indican que la actividad antinociceptiva de los antidepresivos es independiente de la mejoría del estado de ánimo y que está en relación con el efecto de estos fármacos en vías noradrenérgicas y serotoninérgicas ascendentes y descendentes. En modelos animales, sustancias que inhiben selectivamente la recaptación de noradrenalina disminuyen la percepción del dolor; compuestos que inhiben de manera selectiva la recaptación de serotonina no tienen ese efecto pero potencian el efecto antinociceptivo de las que inhiben la recaptación de noradrenalina. Disminuyendo la percepción del dolor se contribuye a mejorar los síntomas depresivos que pudieran coexistir. Una mejoría en los síntomas depresivos que pudieran magnificar la percepción del dolor contribuiría a disminuir esta última; el efecto de algunos fármacos en el sistema límbico puede conducir a mejorar tanto la percepción del dolor como el estado de ánimo. Duloxetina posee acción dual como inhibidor de la recaptación de serotonina y noradrenalina. Investigaciones recientes señalan que no es posible discernir entre el efecto analgésico y antidepresivo de duloxetina. Otros estudios evidencian que el efecto de duloxetina en la percepción del dolor es independiente del efecto antidepresivo. La evolución del caso presentado parece apoyar la hipótesis de que duloxetina contribuye de manera independiente a la mejoría de ambos tipos de síntomas (AU)

Patients with depressive disorders commonly report somatic complaints, such as pain. The improvement in pain perception produced in patients with somatic symptoms of depression under treatment with antidepressants may be related to recovery from depression. Several publications suggest that the antinociceptive activity of antidepressants is independent from mood improvement and is related to the effect of these drugs on the ascending and descending noradrenergic and serotoninergic pathways. In animal samples, selective noradrenaline reuptake inhibitors decrease pain perception; selective serotonin reuptake inhibitors do not have such an effect but they do potentiate the antinociceptive effect of noradrenaline inhibitors. Decreasing pain perception helps to improve the depressive symptoms that may coexist. Improvement in the depressive symptoms that could magnify pain perception would help to reduce this perception. The effect of some drugs on the limbic system could produce improvements in both pain perception and mood state. Duloxetine has a dual action both as a serotonin and as a noradrenaline reuptake inhibitor. While some recent research shows that the analgesic effects cannot be distinguished from the antidepressant effects of this drug, other investigations show that the effect of duloxetine on pain perception is independent from the antidepressive effect. The clinical course of the case presented herein seems to support the hypothesis that duloxetine contributes independently to improvement of both somatic and pain symptoms (AU)

Asociación entre el gen del transportador de la serotonina y rasgos de personalidad en pacientes con trastorno límite de la personalidad evaluados mediante el Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) / Association between the serotonin transporter gene and personality traits in borderline personality disorder patients evaluated with Zuckerman-Kuhlman Personality Questionnaire (ZKPQ)

Introduction. The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5-HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. Method. A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Results. Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. Conclusions. The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder

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Polimorfismos del transportador de serotonina y efecto de fluoxetina sobre la impulsividad y agresividad en el trastorno límite de personalidad / Serotonin transporter polymorphism and fluoxetine effect on impulsiveness and aggression in borderline personality disorder

Introducción. La impulsividad y agresividad son características del trastorno límite de personalidad y están asociadas a una disfunción del sistema serotoninérgico. Polimorfismos del transportador de serotonina han sido vinculados a las conductas agresivas e impulsivas. En depresión el alelo corto (S) se asocia a peor respuesta a los inhibidores selectivos de la recaptación de serotonina (ISRS). El objetivo de este trabajo es estudiar estos polimorfismos para predecir la respuesta de las conductas agresivas e impulsivas a los ISRS en el trastorno límite de personalidad. Método. Cincuenta y nueve pacientes con trastorno límite de personalidad del DSM-IV de acuerdo al International Personality Disorder Examination (IPDE) y sin patología del eje I fueron tratados con fluoxetina en dosis flexibles durante 12 semanas. Los pacientes fueron evaluados mediante la Overt Aggression Scale Modified (OAS-M) al inicio y a las 2, 4, 8 y 12 semanas de tratamiento. Se determinó los polimorfismos L y S de la región promotora del transportador de serotonina. Se comparó la respuesta a fluoxetina de los portadores de LL frente a los portadores de S (LS + SS). Resultados. Los portadores de LL tuvieron mejor respuesta que los portadores de S en reducir las puntuaciones del OAS-M total y en los componentes agresividad e irritabilidad del OAS-M. Conclusiones. Los portadores del alelo L responden mejor a fluoxetina que los portadores de S, de modo similar que en depresión. El alelo S puede representar un factor común de mala respuesta a los ISRS en las patologías asociadas a disfunción del sistema serotoninérgico

Introduction. Impulsiveness and aggressiveness are characteristics of borderline personality disorder and are associated to a serotoninergic system dysfunction. Serotonin transporter polymorphisms have been linked to aggressive and impulsive behaviors. The short allele (S) in depression is associated to a worse response to selective serotonin reuptake inhibitors (SSRI). This study aims to study these polymorphisms to predict the response of aggressive and impulsive behaviors to SSRIs in borderline personality disorder. Method. Fifty-nine patients with DSM-IV borderline personality disorder in accordance with the International Personality Disorder Examination (IPDE) and without axis 1 disease were treated with flexible doses of fluoxetine for 12 weeks. The patients were evaluated with the Overt Aggression Scale Modified (OAS-M) at the beginning and at 2, 4, 8 and 12 weeks of treatment. Polymorphisms L and S of the serotonin transporter promoter region were determined. Response to fluoxetine of the LL carriers versus the S carriers (LS+SS) was compared. Results. LL carriers had a better response than S carriers in the reduction of total OAS-M scores and on the aggressiveness and irritability components of the OAS-M. Conclusions. L-allele carriers responded better to fluoxetine than S carriers, in a similar way as in depression. The S allele may represent a common factor of bad response to SSRI in diseases associated to serotoninergic system dysfunction

Utilización de antidepresivos inhibidores selectivos de la recaptación de serotonina en niños y adolescentes con depresión mayor / Selective serotonin reuptake inhibitors: use in children and adolescents with major depressive disorder

El tratamiento de la depresión en niños y adolescentes es una cuestión sanitaria de primer orden y actualmente asociada a elevada alarma social. En los últimos años han aparecido estudios que ponen en cuestión el uso de los antidepresivos en estas poblaciones del modo en que se ha estado realizando. En este trabajo analizamos la información proporcionada por los organismos oficiales y por las principales revisiones publicadas sobre el tema. Los resultados muestran un aumento del riesgo de desinhibición conductual, irritabilidad, conductas agresivas, autolesiones e incremento de ideación suicida con el uso de los antidepresivos en niños y jóvenes. Se puede añadir que no se han registrado suicidios consumados. Hasta el momento actual sólo disponemos de pruebas de eficacia antidepresiva en el caso de fluoxetina para depresiones moderadas-graves en niños y adolescentes y para los antidepresivos tricíclicos en los adolescentes. Las importantes dificultades metodológicas y la escasez de estudios sólo permiten considerar los resultados como exploratorios y es difícil extraer conclusiones clínicas definitivas, pero son útiles para guiar la investigación futura

Treatment of depression in children and adolescents is a health care question of primary importance and it is presently associated to significant social concern. In recent years some studies have appeared that throw light on the question of the use of antidepressants in these sectors of the population in which they have been used. Information provided by national agencies, associations of health professional’s guidelines and other publications have been reviewed. The results show an increase in aggressive and desinhibitional behavior, irritability, self-injuries and an increase in suicidal motivation with the use of antidepressants in children and adolescents. It can be added that no completed suicides have been recorded. Proof of antidepressant effectiveness only appears in the case of fluoxetine for moderate to severe depressions in children and adolescents and for tricyclic antidepressants in adolescents. The important methodological difficulties and the lack of studies only allow to consider the results as exploratory and it is hard to obtain definitive clinical results, however, they are useful to guide future investigation

Antidepresivos inhibidores selectivos de la recaptación de serotonina durante el embarazo / Selective serotonin reuptake inhibitor antidepressants in pregnancy

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Nuevas perspectivas en el tratamiento del dolor neuropático: duloxetina / New perspectives in the treatment of neuropathic pain: duloxetine

Duloxetina es un nuevo fármaco antidepresivo, que inhibe selectivamente la recaptación de serotonina y de noradrenalina aporta una nueva perspectiva en el tratamiento del dolor neuropático. Se absorbe de manera adecuada tras la administración oral. Se elimina fundamentalmente mediante metabolismo hepático mediado por las isoenzimas del citocromo P450, CYP1A2 y el CYP2D6. La mayoría de los efectos adversos que produce como náuseas, sequedad de boca y estreñimiento son intensidad de leve a moderada, y por lo general desaparecen con la continuación del tratamiento. Actualmente, duloxetina está indicado en el tratamiento de la depresión mayor y del dolor neuropático diabético. Más recientemente ha sido aprobado su empleo para el tratamiento en mujeres de la incontinencia urinaria de esfuerzo moderada a grave. Además su eficacia en otras patologías como la fibromialgia continúa siendo estudiada en diversos ensayos clínicos (AU)

Duloxetine is a novel antidepressant agent reuptake inhibitorof serotonin and norepinephrine, with good perspective inthe treatment of neuropathic pain. Orally administered duloxetineis well absorbed. Elimination of duloxetine is mainlythrough hepatic metabolism involving two CYP450 isozymes,CYP1A2 and CYP2D6. Duloxetine may cause some adverseevents: nausea, dry mouth or constipation. Normally are mildto moderate and they disappear when the treatment continues.Duloxetine is used for treatment of major depressive disorderand diabetic peripheral neuropathic pain.Recently it has also been approved for treatment of stressurinary incontinence moderate to severe in women. It has alsobeing studied in several clinical trials for the treatment of otherkind of pathology, including fibromyalgia (AU)