Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study.

BACKGROUND: Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents. OBJECTIVE: To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs). DESIGN: Retrospective cohort study using a target trial emulation framework. SETTING: 100% Medicare NH sample linked to Minimum Data Set (MDS) from 2010 to 2021. PARTICIPANTS: Long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use. INTERVENTION: Initiating CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for 1 day or more. MEASUREMENTS: Clinical outcomes were worsening pain, physical function, and depression from baseline to quarterly MDS assessments and were analyzed using modified Poisson regression models. The ORAE outcomes included counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose and were analyzed with negative binomial or Poisson regression models. All models were adjusted for baseline covariates via inverse probability of treatment weighting. RESULTS: Among 29 435 identified residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13 [95% CI, 1.09 to 1.17]) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37 [CI, 1.19 to 1.59]), pain-related ED visit (1.49 [CI, 1.24 to 1.80]), and OUD (1.93 [CI, 1.37 to 2.73]), with no difference in physical function, depression, and opioid overdose. LIMITATION: Findings are generalizable to NH populations only. CONCLUSION: Use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents. PRIMARY FUNDING SOURCE: National Institute on Aging.

Metabolic bioactivation of antidepressants: advance and underlying hepatotoxicity.

Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of the 34 antidepressants discussed in this review, four have been withdrawn from the market due to severe hepatotoxicity, and others carry boxed warnings for idiosyncratic liver toxicity. The clinical and economic implications of antidepressant-induced liver injury are substantial, but the underlying mechanisms remain elusive. Drug-induced liver injury may involve the host immune system, the parent drug, or its metabolites, and reactive drug metabolites are one of the most commonly referenced risk factors. Although the precise mechanism by which toxicity is induced may be difficult to determine, identifying reactive metabolites that cause toxicity can offer valuable insights for decreasing the bioactivation potential of candidates during the drug discovery process. A comprehensive understanding of drug metabolic pathways can mitigate adverse drug-drug interactions that may be caused by elevated formation of reactive metabolites. This review provides a comprehensive overview of the current state of knowledge on antidepressant bioactivation, the metabolizing enzymes responsible for the formation of reactive metabolites, and their potential implication in hepatotoxicity. This information can be a valuable resource for medicinal chemists, toxicologists, and clinicians engaged in the fields of antidepressant development, toxicity, and depression treatment.

Changes in Serum Concentration of Antidepressants After Bariatric Surgery and Recommendations for Postbariatric Surgery Antidepressant Therapy.

BACKGROUND: Bariatric surgery affects the absorption of medications including antidepressants, but data regarding these effects are limited. OBJECTIVES: Our objectives were to review publicly available data regarding changes in antidepressant serum concentration following bariatric surgery in order to develop medication dosing recommendations in this patient population. METHODS: A comprehensive literature review was performed utilizing key search terms in Pubmed. Additional data were retrieved from the Food and Drug Administration and DrugBank Online resources. RESULTS: A total of twelve published articles were included in addition to the publicly available data from the Food and Drug Administration and DrugBank. The serum concentration of antidepressants following bariatric surgery demonstrated considerable variability between and within drug classes due to unique pharmacokinetic features, drug preparation, and formulation. Recommendations were developed from published data regarding changes in serum concentration and drug-specific pharmacokinetic data. CONCLUSIONS: To our knowledge, this is the first study to propose medication dose-adjustment recommendations for patients on antidepressants undergoing bariatric surgery. We were limited by the relatively small amount of data available and recommend monitoring patients and use of clinical judgment along with this guidance.

Effects of two commonly used antidepressants amitriptyline and fluoxetine on the pharmacokinetics of abrocitinib in rats.

Abrocitinib is approved to treat moderate-to-severe atopic dermatitis and eliminated mainly through cytochrome P450 (CYP450) enzyme. Two commonly used antidepressants, amitriptyline and fluoxetine, could inhibit the activities of CYP2C19 and CYP3A4. In this study, we developed a new and quick ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantitatively analyzing the plasma concentration of abrocitinib, and further investigated the effects of amitriptyline or fluoxetine on the pharmacokinetics of abrocitinib in rats. The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied according to the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Our result showed that when co-administered with amitriptyline and fluoxetine, the CLz/F of abrocitinib was reduced by 44.4 % and 33.3 %, respectively, while the AUC(0-t) of abrocitinib was increased by 77.7 % and 49.4 %, respectively. It indicated that amitriptyline and fluoxetine could significantly increase the plasma concentration of abrocitinib in rats. Thus, dose adjustment of abrocitinib may be required when it is combined with amitriptyline or fluoxetine in ongoing clinical practice.

Dopaminergic Modulation and Computational ADMET Insights for the Antidepressant-like Effect of N-(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide.

The compound N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), which combines a selenium atom and a benzamide nucleus in an organic structure, has demonstrated a fast antidepressant-like effect in mice. This action is influenced by the serotonergic system and represents a promising development in the search for novel antidepressant drugs to treat major depressive disorder (MDD), which often resists conventional treatments. This study aimed to further explore the mechanism underlying the antidepressant-like effect of SePB by investigating the involvement of the dopaminergic and noradrenergic systems in the tail suspension test (TST) in mice and evaluating its pharmacokinetic profile in silico. Preadministration of the dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally (i.p.)), a nonselective antagonist of dopamine (DA) receptors, SCH23390 (0.01 mg/kg, subcutaneously (s.c.)), a D1 receptor antagonist, and sulpiride (50 mg/kg, i.p.), a D2/3 receptor antagonist, before SePB (10 mg/kg, intragastrically (i.g.)) prevented the anti-immobility effect of SePB in the TST, demonstrating that these receptors are involved in the antidepressant-like effect of SePB. Administration of the noradrenergic antagonists prazosin (1 mg/kg, i.p.), an α1-adrenergic antagonist, yohimbine (1 mg/kg, i.p.), an α2-adrenergic antagonist, and propranolol (2 mg/kg, i.p.), a ß-adrenergic antagonist, did not block the antidepressant-like effect of SePB on TST, indicating that noradrenergic receptors are not involved in this effect. Additionally, the coadministration of SePB and bupropion (a noradrenaline/dopamine reuptake inhibitor) at subeffective doses (0.1 and 3 mg/kg, respectively) produced antidepressant-like effects. SePB also demonstrated good oral bioavailability and low toxicity in computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. These findings suggest that SePB has potential as a new antidepressant drug candidate with a particular focus on the dopaminergic system.

A Combination of Magnoflorine and Spinosin Improves the Antidepressant effects on CUMS Mouse Model.

BACKGROUND: Depression is a common neuropsychiatric disease. As a famous traditional Chinese medicine with significant anti-depressive and sleep-promoting effects, Ziziphi Spinosae Semen (ZSS) has attracted the attention of many researchers. Although it is well known that Magnoflorine (MAG) and Spinosin (SPI) were the main active components isolated from ZSS, there is a lack of research on the combined treatment of depression with these two ingredients. METHODS: The shaking bottle method was used to simulate the human environment for detecting the changes in oil-water partition coefficient before and after the drug combination. Cell viability was evaluated by the MTT assay. To establish a mouse model of depression and insomnia by CUMS method, and then to explore the effect of combined administration of MAG and SPI on depression in CUMS model by observing behavior and analyzing pharmacokinetics. RESULTS: The change in LogP values affected the lipid solubility of MAG and increased the water solubility of SPI, allowing them to penetrate more easily through the blood-brain barrier into the brain. Compared with the model group, MAG-SPI with a concentration of 60 µM significantly increased cell survival rate. In both the TST and FST experiments, the mice showed a decrease in immobilization time. Pharmacokinetic results showed that the pharmacokinetic parameters, Cmax and AUC of MAG and SPI, were increased in the case of combination, which resulted in enhancement of their relative bioavailability and improvement of in vivo effects. CONCLUSIONS: The present study demonstrated that a combination of MAG and SPI had a synergistic antidepressant effect in CUMS mouse model.

Pharmacogenomic Characterization of Childbearing-Aged Individuals With Mood Disorders in a Tertiary Care Perinatal Mental Health Clinic.

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic.Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5- defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects.Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49-0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29-0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect.Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy.

GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents.

The NMDA receptor (NMDAR) antagonist ketamine has shown great potential as a rapid-acting antidepressant; however, its use is limited by poor oral bioavailability and a side effect profile that necessitates in-clinic dosing. GM-1020 is a novel NMDAR antagonist that was developed to address these limitations of ketamine as a treatment for depression. Here, we present the preclinical characterization of GM-1020 alongside ketamine, for comparison. In vitro, we profiled GM-1020 for binding to NMDAR and functional inhibition using patch-clamp electrophysiology. In vivo, GM-1020 was assessed for antidepressant-like efficacy using the Forced Swim Test (FST) and Chronic Mild Stress (CMS), while motor side effects were assessed in spontaneous locomotor activity and on the rotarod. The pharmacokinetic properties of GM-1020 were profiled across multiple preclinical species. Electroencephalography (EEG) was performed to determine indirect target engagement and provide a potentially translational biomarker. These results demonstrate that GM-1020 is an orally bioavailable NMDAR antagonist with antidepressant-like efficacy at exposures that do not produce unwanted motor effects.

Basmisanil, an α5-GABAAR negative allosteric modulator, produces rapid and sustained antidepressant-like responses in male mice.

There is a critical need for safer and better-tolerated alternatives to address the current limitations of antidepressant treatments for major depressive disorder. Recently, drugs targeting the GABA system via α5-containing GABAA receptors (α5-GABAAR) as negative allosteric modulators (α5-NAMs) have shown promise in alleviating stress-related behaviors in preclinical studies, suggesting that α5-NAMs may have translational relevance as novel antidepressant medications. Here, we evaluated the efficacy of Basmisanil, an α5-NAM that has been evaluated in Phase 2 clinical studies as a cognitive enhancer, in a battery of behavioral tests relevant to coping strategies, motivation, and aversion in male mice, along with plasma and brain pharmacokinetic measurements. Our findings reveal that Basmisanil induces dose-dependent rapid antidepressant-like responses in the forced swim test and sucrose splash test without promoting locomotor stimulating effects. Furthermore, Basmisanil elicits sustained behavioral responses in the female urine sniffing test and sucrose splash test, observed 24 h and 48 h post-treatment, respectively. Bioanalysis of plasma and brain samples confirms effective blood-brain barrier penetration by Basmisanil and extrapolation to previously published data suggest that effects were observed at doses (10 and 30 mg/kg i.p.) corresponding to relatively modest levels of α5-GABAAR occupancy (40-65 %). These results suggest that Basmisanil exhibits a combination of rapid and sustained antidepressant-like effects highlighting the potential of α5-NAMs as a novel therapeutic strategy for depression.

Increasing the bioavailability of oral esketamine by a single dose of cobicistat: A case study.

BACKGROUND: Intranasal esketamine is an approved drug for treatment­resistant depression (TRD); however, it is costly and may result in specific adverse effects. In this single case study, we explored if oral esketamine can be a suitable alternative. METHODS: In collaboration with a 39­year­old female with TRD, we compared plasma concentration curves of intranasal (84 mg) and oral (1, 2 and 4 mg/kg) esketamine. Because oral esketamine has a relatively low bioavailability, it results in a different ratio between esketamine and its primary metabolite noresketamine. To increase the bioavailability of oral esketamine, we co­administered a single dose of the cytochrome P­450 (CYP) 3A4 inhibitor cobicistat (150 mg). RESULTS: For all doses administered, oral esketamine resulted in lower esketamine but higher noresketamine peak plasma concentrations compared with intranasal treatment. Using oral esketamine it was not possible to generate a similar esketamine plasma concentration curve as with the intranasal treatment, except when combined with cobicistat (esketamine 2 mg/kg plus cobicistat 150 mg). CONCLUSIONS: Our findings demonstrate that cobicistat effectively increases the bioavailability of oral esketamine. Further research is required in a larger population, especially to investigate the clinical benefit of cobicistat as a booster drug for oral esketamine.

Pharmacokinetics of antidepressants in patients undergoing hemodialysis: a narrative literature review

We conducted a narrative literature review on studies that specifically addressed the pharmacokinetics of antidepressants in patients on hemodialysis. The search included the MEDLINE, LILACS, and Web of Knowledge databases and combined Medical Subject Headings and free-text search terms for chronic kidney disease, end-stage renal disease, renal replacement therapy, depression, and antidepressants; it was limited to studies conducted in humans, with no language or time constraints. The search yielded 212 studies. After screening titles and abstracts, 32 studies were read in full and 11 ultimately met the inclusion criteria and were included in the review. Most of the studies showed no difference in the pharmacokinetics of antidepressant drugs between patients with normal renal function and patients undergoing hemodialysis. However, studies with fluvoxamine and amitriptyline showed that variations in albumin levels might affect serum concentrations of these agents. The included studies have several limitations, and there are many obstacles to the adequate treatment of depression in patients undergoing hemodialysis. Further studies on this topic are needed to support proper treatment of these patients, improving their quality of life and reducing mortality.

Usos potenciales de la mirtazapina en cuidados paliativos más allá de su efecto antidepresivo / Potential use of mirtazapine in palliative care patients beyond from its antidepressant action

La evaluación y el tratamiento de los trastornos psiquiátricos son cruciales en los padecimientos al final de la vida. La depresión y los trastornos de ansiedad son altamente prevalentes y no deben ser tomados como parte de la normalidad en los pacientes en cuidados paliativos, ya que están asociados a disminución de la calidad de vida, así como mayor morbilidad y mortalidad. Las herramientas de tratamiento farmacológico de estos padecimientos incluyen a los antidepresivos tricíclicos o a los inhibidores selectivos de la recaptura de serotonina que pudiesen no ser los más adecuados por sus efectos adversos e interacciones medicamentosas. Uno de los fármacos que se ocupa relativamente poco en estos contextos es la mirtazapina. La mirtazapina es un fármaco aprobado para el tratamiento de la depresión que se ha probado tiene un inicio de acción más rápido y mayor efectividad que diversos otros antidepresivos. Su mecanismo de acción es distintivo, pues tiene al antagonismo del receptor alfa-2 adrenérgico y el antagonismo del receptor 5-HT2a y c como sus principales actividades sin involucrar a la inhibición del transportador de serotonina. Además cuenta con el bloqueo del receptor 1 de histamina y del receptor 5-HT3 dentro de sus afinidades que le proporcionan actividad como hipnótico-sedante, antiemético y orexigénico. Por su mecanismo noradrenérgico y serotoninérgico también tiene efectos sobre el dolor crónico. Estos factores pueden ser potencialmente útiles en los pacientes tratados en unidades de cuidados paliativos y generarían una reducción de la polifarmacia o del uso de fármacos que pudiesen generar efectos adversos indeseables en esta población. Esta revisión tiene la finalidad de presentar la evidencia del uso de este fármaco en diversos contextos relacionados con la atención de los pacientes en cuidados paliativos, principalmente aquellos que se encuentran al final de la vida, así como establecer su perfil de seguridad en comparación con los antidepresivos clásicamente utilizados (AU)

Evaluation and treatment of psychiatric disorders is crucial in palliative care patients at the end of life. Depression and anxiety disorders are highly prevalent and should not have been taken as normal in palliative care patients, as they are associated with decreased quality of life and increased morbidity and mortality. The pharmacological treatment of these disorders include selective serotonin reuptake inhibitors and tricyclic antidepressants that should not be the most suitable options because adverse effects and drug interactions associated with them. One of the drugs that is not used often in these contexts is mirtazapine. Mirtazapine is an approved drug for the treatment of depression that has proven to have a faster onset of action and greater effectiveness than several other antidepressants. Its mechanism of action is distinctive because alpha2 adrenergic receptor antagonism and 5-HT2a-c receptor antagonism are the main antidepressant mechanism without involving inhibition of the serotonin transporter. It also has activity as an antagonist of the histamine 1 and the 5-HT3 receptors which produce its hypnotic-sedative, antiemetic and orexigenic properties. By its noradrenergic and serotonergic mechanism also has effects on chronic pain. This factors may be potentially useful in patients treated in palliative care units and also, could reduce polypharmacy or the use of drugs that are likely to generate undesirable adverse effects. The purpose of this review is to show evidence of the use of this drug in various contexts related to palliative care patients, mainly those at the end of life, as well as to establish their safety profile in comparison with tipically used antidepressants (AU)

Venlafaxina en el tratamiento del dolor neuropático / Venlafaxine in the treatment of neuropathic pain

Introducción: La venlafaxina fue el primer antidepresivo inhibidor de la recaptación de serotonina y noradrenalina autorizado en España. Aunque no tiene indicación en ficha técnica en el tratamiento del dolor neuropático, hay guías de práctica clínica en las que la venlafaxina aparece en primera o segunda línea de tratamiento. Desarrollo: Tras una búsqueda bibliográfica, en este artículo se resumen los datos farmacológicos más relevantes de la venlafaxina, así como la bibliografía específica de este fármaco en dolor neuropático. Conclusiones: La venlafaxina es un fármaco seguro y bien tolerado para el tratamiento sintomático del dolor neuropático. Aunque la evidencia actual es bastante alentadora (en dosis de al menos 150 mg/día), son necesarias nuevas investigaciones para ampliar estos hallazgos, particularmente cuando se compara con otros posibles agentes farmacológicos

Introduction: Venlafaxine was the first the first serotonin norepinephrine reuptake inhibitor antidepressant to authorized in Spain. Although there is no indication in the data sheet in the treatment of neuropathic pain, there are clinical practice guidelines in which venlafaxine appears in the first or second line of treatment. Development: Following a literature search, this article summarizes the most relevant pharmacological data of venlafaxine, as well as the specific literature of this drug in neuropathic pain. Conclusions: Venlafaxine is a safe and well tolerated drug for the symptomatic treatment of neuropathic pain. Although the current evidence is quite encouraging (at doses of at least 150 mg/day), further research is needed to extend these findings, particularly when is compared to other possible pharmacological agents

Antidepresivos en la tercera edad / Antidepressants in the elderly

La depresión en el anciano es una enfermedad frecuente, compleja y cambiante. Además sufren con más frecuencia recaídas y requieren cursos más largos de tratamiento. Es un reto su abordaje habida cuenta de otros factores concurrentes que complican su tratamiento además de la propia peculiaridad de la psicopatología. Es importante tener un esquema básico de los antidepresivos que nos ayude desde la atención primaria a tratar con garantías esta enfermedad tan frecuente. No hay ningún fármaco libre de problemas y hay que conocer las características de los mismos para poder realizar la elección más adecuada dependiendo de la eficacia, seguridad y tolerabilidad (AU)

Depression in the elderly is a changing, difficult and common disorder. At this age, there are more relapses and more long-life treatment is required. The pharmacology approach is a challenge because of concurrent factors that make their treatment more difficult. It is very important to have a basic antidepressant scheme, in order to help treat this disorder with efficiency and success from Primary Care. There are no drugs without side effects, and their characteristics have to be known in order to make the right selection depending on effectiveness, safety and tolerance (AU)

Experiencia de cambio de marcas comerciales de lamotrigina en una paciente ambulatoria del Hospital Vilardebó / Experience of changing commercial brands of lamotrigine in an outpatient of the Vilardebó Hospital

Se desarrolló una experiencia en una pacientede cambio entre dos marcas comerciales de lamotrigina: Lamictal (referencia) y Epilepax (test). Esto fue motivado por notificaciones sobre sospecha de falta de eficacia de una de las citadas presentaciones farmacéuticas utilizada en el Hospital Vilardebó. Se realizó la comparación de las curvas salivales de lamotrigina versus tiempo para las dos marcas, determinándose parámetros clínicos, farmacocinéticos y de seguridad. La experiencia de cambio entre las dos marcas en la paciente no evidenció diferencias en ninguno de los parámetros mencionados.

An experience was developed in a patient of change between two commercial brands of lamotrigine: Lamictal (reference) and Epilepax (test). This was motivated by notifications on suspicion of lack of efficacy of one of the aforementioned pharmaceutical presentations used in the Vilardebó Hospital. The comparison of salivary curves of lamotrigine versus time for the two brands was made, determining clinical, pharmacokinetic and safety parameters. The experience of change between the two brands in the patient did not show any differences in any of the mentioned parameters.

A preliminary analysis of association betweenplasma microRNA expression alteration andsymptomatology improvement in Major DepressiveDisorder (MDD) patients before andafter antidepressant treatment

Background and Objectives: Currently, there is a serious need to find practical biomarker(s) for Major Depressive Disorder (MDD) therapeutic target(s). This study aimed to investigate the association between microRNA (miRNA, miR) expression level in Peripheral Blood Mononuclear Cells (PBMCs) and symptomatology improvement in MDD patients before and after six-week antidepressant treatment. Methods: By using an Affymetrix array that covers 723 human miRNAs, 26 miRNAs were identified with significantly altered expression in PBMCs in MDD patients, of which10 miRNAs were selected for quantitative real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) study. Twenty out of all the 81 MDD patients were selected formiRNA expression levels testing and symptomatology assessments before and after sixweektreatment. Results: Compared with the control group, the expression levels of miR-26b, miR-4743, miR-4498, miR-4485 and miR-1972 of the MDD group were significantly higher(P < 0.05); the changes of expression levels of miR-4743, miR-4498, miR-4485 and miR-1972 were positively related to retardation improvement (P < 0.05), and the change of expression level of miR-26b negatively to the improvement of day and night change(P < 0.05); regression analysis result demonstrated that the alteration of miR-4485 expression accounted for 28.8% of retardation improvement (P < 0.05). Conclusions: These five miRNAs (miR-4743, miR-4498, miR-4485, miR-1972 andmiR-26b) may serve as biomarker for MDD diagnosis and therapeutic targets for MDDtreatment (AU)

Boticarium / No disponible

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Antidepressant and skeletal muscle relaxant effects of the aqueous extract of the Prosopis cineraria

The aqueous leaves extract of Prosopis cineraria (AEPC) is used traditionally for the treatment of various CNS disorder. The purpose of this study was to evaluate the extract for antidepressant and skeletal muscle relaxant activity. The antidepressant effect of the extract was evaluated using Forced swim test (FST). The immobility periods of control and treated mice were recorded. The antidepressant-like effect of tested compound was compared to that of imipramine (15 mg/kg. p.o). Muscle relaxant property was studied using rotarod apparatus and total fall off time for standard and control group was recorded. Phytochemical screening revealed the presence of saponins, flavonoids, alkaloids, glycosides, tannins and phenolic compounds. The leaf extract at doses of 200 mg/kg significantly decreased the duration of immobility time in FST. The efficacy of tested extract was found to be comparable to that of imipramine. Our results suggested that the aqueous extract of Prosopis cineraria leaves exerts antidepressant-like effect.

O extrato aquoso de folhas de Prosopis cineraria (AEPC) é utilizado, tradicionalmente, para o tratamento de várias disfunções do SNC. O propósito desse estudo foi avaliar o extrato quanto às atividades antidepressiva e relaxante muscular esquelética. O efeito antidepressivo do extrato foi avaliado usando o teste do nado forçado (FST). Registraram-se os períodos de imobilidade dos camundongos controle e dos tratados. O efeito antidepressivo do composto testado foi comparado com a imipramina ((15 mg/kg. p.o). A propriedade relaxante muscular foi estudada usando o cilindro giratório e o tempo total de queda para os grupos padrão e controle foram registrados. A triagem fitoquímica revelou a presença de saponinas, flavonoides, alcaloides, glicosídeos, taninos e compostos fenólicos. O extrato da folha em doses de 200 mg/kg diminui significativamente a duração do tempo de imobilidade no FST. A eficácia do extrato testado foi comparável àquela da imipramina. Nossos resultados sugeriram que o extrato aquoso das folhas da Prosopis cineraria exerce efeito semelhante ao antidepressivo.

Bases neuroquímicas de la depresión. Un modelo médico de la enfermedad depresiva / Neurochemical bases of depression. A medical model of depressive disorders

El conocimiento del mecanismo de acción de los fármacos antidepresivos provocó una notable actividad investigadora acerca de la implicación de las monoaminas en la patogenia de la depresión. A lo largo de las últimas décadas y en relación a los medios tecnológicos disponibles y al "efecto moda" presente en las revistas científicas se ha generado suficiente grado de conocimiento como para relacionar la hipofunción de al menos 4 neurotransmisores a lo que llamaremos síntomas nucleares de la depresión. La hipofunción serotoninérgica se ha podido vincular, además de al humor depresivo, a la baja tolerancia al estrés y a la intolerancia al dolor; la de su metabolito, la melatonina, a la pérdida de la arquitectura del sueño y al aplanamiento de todos los ritmos circadianos. En cuanto a las catecolaminas, la noradrenalina y la dopamina a la disfunción cognitiva y a la incapacidad de sentir placer respectivamente. La elaboración por parte del paciente de estos síntomas básicos o nucleares dará lugar a la constelación de síntomas que caracterizan el episodio depresivo (AU)

Knowledge of the mechanism of action of antidepressant drugs prompted intense research activity on monoamine involvement in the pathogenesis of depression. Over the last few decades and related to the technological means available and the "fashion effect" in scientific journals, sufficient knowledge has been generated to relate hypofunction of at least 4 neurotransmitters to what we call the core symptoms of depression. Serotonergic hypofunction has been linked to depressed mood, low stress tolerance and pain intolerance, while its metabolite melatonin has been linked to loss of sleep architecture and flattening of all circadian rhythms. Catecholamines, norepinephrine and dopamine have been related to cognitive dysfunction and an inability to feel pleasure, respectively. The development of these basic or core symptoms will lead to the constellation of symptoms characterizing depressive episodes (AU)

¿En qué consiste el efecto procognitivo de los antidepresivos? / What is the pro-cognitive effect of antidepressants?

La disfunción cognitiva en el trastorno depresivo mayor (TDM) abarca varios dominios incluyendo, pero no limitados, a la función ejecutiva, la memoria verbal y la atención. Por otra parte, la disfunción cognitiva es una manifestación residual frecuente en la depresión y puede persistir durante la fase de remisión de los síntomas afectivos y somáticos. Los déficits cognitivos también pueden impedir la recuperación funcional incluyendo la capacidad de recuperación laboral, social y familar. Los nuevos antidepresivos como vortioxetina parecen conseguir una importante mejoría en dominios cognitivos alterados en el TDM y superan el efecto antidepresivo a este nivel de los antidepresivos convencionales y los antidepresivos selectivos. Los objetivos generales de este artículo de opinión son evaluar críticamente los efectos de los antidepresivos disponibles, así como las nuevas dianas terapéuticas sobre la disfunción neurocognitiva en el TDM (AU)

Cognitive dysfunction in major depressive disorder (MDD) spans multiple domains, including-but not limited to-executive function, verbal memory and attention. Moreover, cognitive dysfunction is a common residual manifestation in depression and may persist during the remission phase of affective and somatic symptoms. Cognitive deficits can also prevent functional recovery, including the ability to work, and social and familar recovery. New antidepressants such as Vortioxetine seem to achieve a significant improvement in the cognitive domains that are altered in MDD, thus providing additional benefits over conventional and selective antidepressants. The general objectives of this article are to critically assess the effects of available antidepressants and to discuss new therapeutic targets on neurocognitive dysfunction in MDD (AU)