Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Anti-proliferative effects of paroxetine alone or in combination with sorafenib in HepG2 cells

Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib is the first approved drug for the treatment of advanced HCC. Depression is frequent in cancer patients. Moreover, sorafenib might exert depression as an adverse drug reaction and paroxetine, a selective serotonin reuptake inhibitor, is a recommended pharmacotherapy. This study aimed to investigate the potential synergistic effects of paroxetine and sorafenib on HepG2 cell proliferation and death. Paroxetine and sorafenib were administered to HepG2 cells as single-agents or in combination. Cell viability was determined with XTT cell viability assay. Cellular apoptosis and DNA content were assessed by flow cytometry. The expression of anti-apoptotic Bcl-2 was examined by immunofluorescence confocal microscopy. A lower dose of sorafenib was found to be required to inhibit cell proliferation when in combination with paroxetine. Similarly, the coadministration enhanced cellular apoptosis and resulted in cell cycle arrest. Confocal imaging revealed a remarkably lower cell density and increased expression of Bcl-2 following combined treatment of paroxetine with sorafenib. To our knowledge, this is the first study demonstrating the synergistic effect of paroxetine and sorafenib in HCC and might provide a potentially promising therapeutic strategy.

La cara oculta del estudio 329 y la manipulación de la evidencia científica / Study's 329 hiddens face and scientifics evidence manipulation

El emblemático ensayo clínico 329, financiado por Smith Kline Beecham (actualmente GlaxoSmith-Kline) y publicado en2001, permitió posicionar a la paroxetina como un tratamiento efectivo y seguro para la depresión mayor en adolescentes. En la presente editorial el autor describe los sucesos ocurridos luego de su publicación, partiendo de los cuestionamientos iniciales respecto de su eficacia, hasta llegar a los resultados de su reciente reanálisis (llevando adelante por la iniciativa internacional RIAT), el cual concluyo que dicho fármaco no solo no provee un beneficio adicional al placebo para la condición y población utilizada, sino que además se asocia a efectos adversos sustanciales que no habían sido reportados en el informe original. Se exploran además las repercusiones de este suceso en la comunidad científica y se hace un señalamiento de la necesidad de permitir el acceso a las bases de datos originales que sustentan los resultados y conclusiones de las investigaciones publicadas, como mecanismo de transparencia superador a la revisión por pares. (AU)

The emblematic 329 study, funded by Smith Kline Beecham (now GlaxoSmith-Kline) and published in 2001, allowed to position paroxetine as an effective and safe treatment for major depression in adolescents. In this editorial, the author describes the events after its publication, from the initial concerns about its effectiveness, to the results of its recent reanalysis (accounted by the international RIAT initiative), which concluded that the drug not only does not provide an additional benefit than placebo, but is also associated with significant adverse effects that were not reported in the original report. It also explores the repercussions generated in the scientific community by this event, pointing out the need to allow access to original databases that support the findings and conclusions of published research, as an overcoming mechanism for transparency to the traditional peerreview. Agustín Ciapponi Study's 329 hiddens face and scientifics evidence manipulation. (AU)

Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine

The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4 percent in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95 percent; P = 0.001). The most common adverse events were drowsiness/fatigue (57 percent), memory/concentration difficulties (24 percent), and sexual dysfunction (11 percent) in the clonazepam group and drowsiness/fatigue (81 percent), sexual dysfunction (70 percent), and nausea/vomiting (61 percent) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.

Síndrome serotonínico secundario al uso de paroxetina en una paciente en hemodiálisis periódica / Serotonin syndrome secondary to the use of paroxetine in a patient under systematic hemodißlisis regime

El síndrome serotonínico es una situación clínica que se caracteriza por alteraciones del estado mental, inestabilidad autonómica y anormalidades neuromusculares como tremor, hiperreflexia o mioclonías y que puede aparecer como complicación por el uso de medicamentos que incrementan los niveles de serotonina como los inhibidores de la recaptación selectiva de serotonina, o la asociación de estos con otras drogas como los inhibidores de la monoaminooxidasa. Se presenta el caso de una paciente de 78 años de edad con insuficiencia renal crónica terminal por hipertensión arterial, bajo tratamiento de hemodiálisis periódica, que desarrolla un síndrome serotonínico secundario al uso de 20 mg diarios de paroxetina que se comenzaron a administrar por un cuadro depresivo, previamente fueron descartadas enfermedades infecciosas, metabólicas, neurológicas y la sobredosis de algún medicamento. La paciente mejoró después de la suspensión de la paroxetina.

Serotonin syndrome is a clinical situation characterized by altered state of mind, autonomic instability and neuromuscular anomalies such as tremor, hyperreflexia or myoclonia, which are symptoms that may occur as a result of the use of drugs that increase serotonin levels when acting as selective serotonin reuptake inhibitors or their association with other drugs as monoaminoxidase inhibitors. This paper presented the case of a 78 years-old female patient suffering from terminal chronic renal failure caused by hypertension, low therapy of periodic hemodyalisis which gave rise to serotonin syndrome secondary to the daily use of 20 mg paroxetine prescribed for a depression condition. Infectious, metabolic, neurological diseases as well as some drug overdose were ruled out. The patient improved her condition after paroxetine treatment was suspended.

Síndrome serotoninérgica associada ao uso de paroxetina: relato de caso / Serotonin syndrome associated to the use of paroxetine: case report

Relatamos um caso de síndrome seretoninérgica pelo uso de inibidor da recaptação da serotonina, a paroxetina. Tal síndrome por esta droga, sem combinações, ainda não tinha sido descrita na literatura.

Interaçöes medicamentosas: Antidepressivos novos e o sistema citocromo P450 / Drug interactions: Newer antidepressants and the cytochrome P450 system

A maioria dos fármacos sofre biotransformaçäo, frequentemente envolvendo a oxidaçäo no fígado. Recentemente, descobriu-se que algumas enzimas do sistema enzimático citocromo P450 säo responsáveis pelos primeiros passos metabólicos d maioria dos fármacos. Algumas drogas podem inibir enzimas P450 e esta inibiçäo pode levar a interaçöes potenciais com outros fármacos. Muitos estudos têm focalizado o sistema citocromo P450 e seu papel em interaçöes medicamentosas potnciais. Este artigo apresenta as evidências in vitro e in vivo da inibiçäo de enzimas do sistema citocromo P450 (1A2, 2C9, 2C19, 2D6, 3A3/4) por antidepressivos recentemente introduzidos no mercado (citalopram, fluoxetina, fluvoxamina, nefazodona, paroxetina, sertralina e venlafaxetina) e sua relevância clínica potncial

Bruxismo associado ao uso de antidepressivos inibidores seletivos da recaptaçäo de serotonina: relato de quatro casos / SSRI-associated bruxism: case report of 4 patients

Bruxismo ocorre entre 5 a 20 por cento da populaçäo em alguma fase da vida. Frequentemente está associado a sintomas ansiosos, estresse e transtornos do sono. A associaçäo bruxismo e efeitos adversos e transtornos do sono. A associaçäo bruxismo e efeitos adversos de drogas psicotrópicas é escassa. Relatamos quatro casos clíncos de pacientes que começaram a apresentar bruxismo após o uso de antidepressores ISRS - paroxetina, citalopram e sertralina. Esses casos servem como alerta para maiores investigaçöes clínicas no sentido de confirmara associaçäo e verificar a sua magnitude

Dos inhibidores de recaptación de serotonina en eyaculación precoz / 2 serotonin reuptake inhibitors in premature ejaculation

La eyaculación precoz es muy frecuente, pero sólo consultan aquellos hombres que lo sienten como problema. Los inhibidores de la recaptacción de Serotonina actuan a nivel de la vesícula sináptica impidiendo la recaptación del neurotransmisor, permitiendo así una mayor utilización por la neurona sináptica

Disfunçäo sexual associada ao uso de antidepressivos / Sexual dysfunction associated with antidepressant therapy

A disfunçÝo sexual é um efeito colateral bastante conhecido relacionado ao uso de antidepressivos. Noventa pacientes em uso de vários antidepressivos foram avaliados. Observou-se que a maioria dos casos nÝo cumpriam seus programas terapêuticos devido à disfunçÝo sexual. As principais alteraçSes encontradas foram diminuiçÝo da libido, retardo ou inibiçÝo da ejaculaçÝo, inibiçÝo do orgasmo, disfunçÝo erétil e orgasmo doloroso

Estudo randomizado, duplo-cego, controlado de paroxetina e fluoxetina no tratamento de pacientes com depressäo maior associada a ansiedade / Study randomized

Nos últimos anos, a literatura médica mundial reportou o desenvolvimento de novas drogas com efeito antidepressivo. Entre elas, estäo os ISRSs (inibidores seletivos da recaptaçäo de serotonina). Os autores apresentam um estudo randomizado, duplo-cego, no qual foram avaliadas a eficácia e a segurança de dois agentes, paroxetina e fluoxetina, no tratamento da depressäo maior e da depressäo maior associada à ansiedade. Foram usadas as escalas MADRS e HAM-A para avaliar a ansiedade; à gravidade da doença e a evoluçäo do tratamento foram usados para avaliar a melhora clínica global. Para avaliar a segurança, os sinais físicos, ECG, exames laboratoriais e a ocorrência de efeitos adversos foram as variáveis usadas. Ambos os agentes foram eficazes e bem tolerados no tratamento da depressäo maior e da depressäo maior associada a ansiedade