Effects of paroxetine on the safety of mothers and infants in the second and third trimesters of pregnancy：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.

Effects of repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride on executive function in depressed adolescents with non-suicidal self-injury / 中国基层医药

Objective:To investigate the effects of repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride on executive function in depressed adolescents with non-suicidal self-injury.Methods:The clinical data of 120 depressed adolescents with depressive disorders who were admitted to The Second Hospital of Jinhua from August 2021 to July 2022 were retrospectively analyzed. They were randomly assigned to undergo treatment either with paroxetine hydrochloride (control group, n = 60) or repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride (observation group, n = 60). All patients were treated for 2 months. Hamilton Depression Rating Scale-24 (HAMD-24) score, Non-suicidal Self-injury Behavior and Function Scale for Adolescents (ANSSIQ) score, executive function, brain-derived neurotrophic factor, 5-hydroxytryptamine, and clinical efficacy were determined in each group. Results:After treatment, the Hamilton Depression Rating Scale-24 score in the observation group was significantly lower than that in the control group [(15.85 ± 1.08) points) vs. (18.72±1.21) points, t = 13.71, P < 0.001). After treatment, the number of self-injury attacks, number of self-injury impulsions, and the intensity of self-injury thought within 2 weeks in the observation group were significantly lower than those in the control group ( t = 3.42, 3.03, 1.92, all P < 0.05). The scores of the Trail Making Test, Stroop Word test, Stroop Color test, and Stroop Color-Word Interference Test were significantly higher in the observation group than those in the control group ( t = 2.66, 3.33, 3.97, 4.64, all P < 0.01). Brain-derived neurotrophic factor and 5-hydroxytryptamine levels in the observation group were (11.45 ± 1.79) μg/L and (136.68 ± 11.90) μg/L, respectively, which were significantly higher than (9.06±2.21) μg/L and (124.82 ± 10.34) μg/L in the control group ( t = 6.51, 5.83, both P < 0.001). The total response rate in the observation group was significantly higher than that in the control group (91.7% vs. 78.3%, Z = 2.73, P = 0.006). Conclusion:Repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride is highly effective on depressive disorders in adolescents with non-suicidal self-injury. The combined therapy can reduce symptoms, improve executive function and cognitive function, and optimize serological indicators, and thereby deserves the clinical promotion.

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.

Effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder / 中国医师进修杂志

Objective:To compare the effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder (GAD).Methods:Ninety-six patients with GAD treated in Zaozhuang Mental Health Center from January 2019 to September 2020 were selected and randomly divided into the paroxetine group (treatment with oral paroxetine) and the milnacipran group (treatment with oral milnacipran), each group with 48 cases. A course of treatment consists of 4 weeks. After 3 months of regular medication, the clinical efficacy, Hamilton Anxiety Scale (HAMA) scores, visual analogue scale (VAS) scores, migraine-specific quality of life questionnaire (MSQ V2.1) scores, and Headache Impact Test-6 (HIT-6) scores were compared between the two groups. Adverse reactions during the treatment were recorded in both groups.Results:The total effective rate in the milnacipran group at 4 weeks and 3 months after treatment were significantly higher than those in the paroxetine group: 47.92%(23/48) vs. 22.92%(11/48), χ2 = 6.56, P<0.05; 75.00%(36/48) vs. 51.47%(26/48), χ2 = 4.55, P<0.05. After treatment for 4 weeks and 3 months, the HAMA scores, VAS scores, MSQ V2.1 scores and HIT-6 scores in the milnacipran group were significantly lower than those in the paroxetine group ( P<0.05). The difference of incidence of adverse reactions in the two groups had no statistical significance ( P>0.05). Conclusions:For patients with GAD, the treatment effect of milnacipran is more significant than paroxetine, which can not only reduce patients′ anxiety state and headache degree, but also improve their specific quality of life, with high safety.

Paroxetine alone versus paroxetine combined with gabapentin in patients with somatoform disorders / 中国医师杂志

Objective:To compare the efficacy and safety of paroxetine alone and paroxetine combined with gabapentin in patients with somatoform disorder (SFD).Methods:From July 2018 to December 2020, 108 adult patients with SFD were prospectively selected from the psychological clinic of Jining First People′s Hospital. All patients were divided into the control group (52 cases) and the observation group (56 cases) according to the random number table method. The control group only received paroxetine, and the observation group received paroxetine combined with gabapentin for 12 weeks. Before treatment, at the end of treatment and at the 3-month follow-up after treatment, the levels of anxiety, depression and quality of life in the two groups of SFD patients were assessed by Symptom Checklist 90 (SCL-90), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and the Short Form-36 Health Survey (SF-36), respectively. Adverse event during treatment was recorded with Treatment Emergent Symptom Scale (TESS). At the end of treatment and at the 3-month follow-up after treatment, the therapeutic efficacy was evaluated with the patient′s Global Impression of Change (GIC).Results:At the end of treatment, GIC scores of the control group and the observation group were 3 (2-4) and 2 (1.25-3) respectively ( Z=2.081, P=0.037), and the treatment efficiency (GIC score ≤3) was 65.4%(34/52) and 83.9%(47/56), respectively, with a statistically significant difference (χ 2=4.945, P=0.026). Compared with that before treatment, the SCL-90, HAMA and HAMD scores of the two groups at the end of treatment were significantly reduced (all P<0.05); the SCL-90 somatization and anxiety factor scores of the observation group were lower than those of the control group (all P<0.05), and the HAMA somatization anxiety score of the observation group at the end of treatment was lower than that of the control group ( P<0.05). Compared with that before treatment, the scores of physical health and mental health in the two groups at the end of treatment and 3 months follow-up after treatment were significantly increased (both P<0.05), but there was no significant difference between the two groups (both P<0.05). There was no statistical difference in the total incidence of adverse events between the two groups ( P=0.085), but the incidence of vertigo in the observation group was significantly higher than that in the control group (χ 2=4.405, P=0.036). Conclusions:Paroxetine combined with gabapentin can further increase the effective rate of paroxetine treatment and improve the anxiety of SFD patients, but it has no significant impact on the quality of life, and has the potential risk of increasing dizziness, lethargy and other adverse reactions.

Observation of intestinal flora in patients with depression before and after antidepressant treatment based on 16S rDNA high-throughput sequencing analysis / 中国医师杂志

Objective:To observe the results of 16S rDNA high-throughput sequencing analysis of intestinal flora in patients with depression before and after antidepressant treatment.Methods:94 patients with major depression treated in the First Hospital of Shanxi Medical University from January 2020 to December 2020 were selected as the research objects. All patients were treated with paroxetine hydrochloride for 12 weeks. Fecal samples were collected before and after treatment. The patients were divided into effective group and ineffective group according to the treatment effect. 16S rDNA high-throughput sequencing was used to detect the changes of flora before and after treatment.Results:There was significant difference in age and gender between the two groups (all P<0.05). There was no significant difference in α diversity index such as Chao1, PD and Shannon index between effective group and ineffective group before and after treatment (all P>0.05). β diversity analysis showed that there was a graphical difference between the effective group and the ineffective group at baseline, but it did not show statistical significance after adjusting for age and gender (Adonis, P=0.078). Compared with the ineffective group, the effective group had fecal bacilli enrichment at baseline. β-diversity analysis showed that there was no clear pattern of microbiota changes in the effective group ( P=0.142) and ineffective group ( P=0.127) from baseline to post-treatment. After treatment, the abundance of Roche bacteria in the effective group increased significantly ( P=0.013, Cohen′s d=1.90), while the abundance of Flavonifractor decreased significantly ( P=0.01, Cohen′s=5.84). Before and after treatment, the samples of the ineffective group did not identify the genus with diversity through DESeq2. The logarithm ratio of the top ranked genera (top 12%) to the bottom ranked genera (bottom 12%) in the ineffective group increased significantly ( P=0.027, Cohen′s=1.1). Conclusions:The baseline fecal microbiota status may have an impact on the treatment outcome of depression, and improving the intestinal microbiota status may contribute to the remission of depression.

Study on the effect of relaxation training in the treatment of patients with obsessive-compulsive disorder / 中国实用护理杂志

Objective:To explore the effect of relaxation training in the treatment of patients with obsessive-compulsive disorder.Methods:From January 2017 to June 2018, 90 patients with obsessive-compulsive disorder were admitted to the fourth ward of the Mental Health Center of Shanghai Jiaotong University School of Medicine. According to the random number table method, they were divided into the control group and the intervention group with 45 cases each. The control group was given medication, and the intervention group used relaxation training on the basis of the control group. The obsessive-compulsive disorder scores, quality of life, depression, and anxiety of the two groups were compared before and after treatment.Results:The obsessive thinking and compulsive behavior scores of the control group after treatment were (14.02±3.12) and (15.01±2.45) points; the intervention group was (11.91±3.01) and (12.23±2.34) points after treatment, and lower than the control group ( t values were 3.265, 5.504, P<0.05 or 0.01). The quality of life score of the control group after treatment was (283.64±51.28) points; the intervention group was (305.67±49.28) points after treatment, and the intervention group was higher than the control group after treatment (t value was -2.078, P<0.05). After treatment, the scores of the depression scale and anxiety scale of the control group were (12.35±2.89) and (15.35±4.03) points; the intervention group was (8.05±1.72) and (10.35±3.65) points after treatment, and the intervention group after treatment all lower than the control group ( t values were 8.577, 6.169, P<0.01). Conclusion:Using relaxation training combined with conventional drugs to treat patients with obsessive-compulsive disorder can improve obsessive-compulsive symptoms, improve quality of life, and relieve negative emotions.

Does Propolis improve sperm quality in Paroxetine-Induced Sexual Dysfunction in male Wistar rats?

@#Propolis is a resinous product collected by honey bees for construction of hives. It is locally used as remedy for several ailments including various degrees of sexual dysfunctions. This study investigated the protective property of propolis in improving sperm quality in paroxetine-induced sexually impaired male Wistar rats. Forty-two male rats were divided into 7 groups of 6 rats each. Groups I (normal saline), II (administered paroxetine only for two weeks), III (Sildenafil), IV (low dose propolis), V (moderate dose propolis), VI (high dose propolis), and group VII (propolis+sildenafil). There was significant (p< 0.05) increase in sperm count in group VI, no significant (p>0.05) change in sperm count of group VII, but significant decrease in the other groups compared to control. There was significant (p< 0.05) reduction in sperm motility of rats in groups II, III, and IV, compared to significant (p< 0.05) increase in sperm motility of rats in groups VI and VII, but there was no significant (p>0.05) change in group V. The total sperm abnormality in groups II, III and IV showed significant (p<0.05) increase, while there was significant (p<0.05) reduction in sperm abnormality of groups VI and VII compared to control, and no significant (p>0.05) difference seen in group V. The plasma testosterone levels were significantly (p<0.05) reduced in groups II, III and IV, compared to significant (p< 0.05) increase in plasma testosterone level in groups VI and VII, but no significant (p> 0.05) difference in plasma testosterone in group V. The results indicate that high doses of propolis caused significant increase in plasma testosterone, and there was improvement in sperm count and motility as was obtained by the analysis of seminal fluid (SFA).

Clinical Observation on Shiwei Wendantang in Treating Post-ischemic Stroke Depression of Heart and Gallbladder Qi Deficiency Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Shiwei Wendantang on post-ischemic stroke depression of heart and gallbladder Qi deficiency syndrome. Method:The 80 patients with post-ischemic stroke depression of heart and gallbladder Qi deficiency syndrome were divided into two groups by random number table. 40 cases in control group received oral administration of antidepressant Paroxetine, 20 mg·d-1, and 40 cases in observation group received Shiwei Wendantang, 1 dose/day. The treatment course was 4 weeks in both groups. The clinical efficacy, hamilton depression scale (HAMD-17) score, serum C-reactive protein (CRP), homocysteine (Hcy) level, traditional Chinese medicine(TCM) syndrome score and quality of life score of two groups were observed and compared. Result:After treatment, the curative effect of observation group was better than that of the control group (Z=-2.104，P<0.05), and the total effective rate in observation group was significantly higher than that of control group（χ2 =5.00，P<0.05）. After treatment, the scores of each factor of HAMD-17 scale in observation group were significantly decreased (P<0.05), and the scores of factors of HAMD-17 scale in the control group were also significantly decreased (P<0.05) except despair and anxiety. The decrease of scores in the observation group was more obvious than that in the control group (P<0.05). After treatment, the values of serum CRP and Hcy in two groups were decreased significantly (P<0.01）,and the values of serum CRP and Hcy in observation group were also decreased significantly (P<0.01）.After treatment, the scores of TCM syndromes in observation group were decreased significantly (P<0.01）， while in control group, only the score of urination was significantly decreased（P<0.05）. The scores of quality of life in observation group were all significantly higher than those before treatment (P<0.01）. The scores of SF-36 Health Survey Form in the control group were significantly decreased except for energy and social function (P<0.05). The scores of physical function, physical intelligence, physical pain, social function, and mental health in observation group were significantly higher than those in the control group (P<0.05). Conclusion:As compared with the conventional western medicine treatment, the application of Shiwei Wendantang in the treatment of post-ischemic stroke depression of heart and gallbladder Qi deficiency syndrome, can further reduce the degree of depression of patients, improve the symptoms of depression, and improve the quality of life, with more significant clinical efficacy and comprehensive effect.

Aphrodisiac Effects of Aqueous Extracts of Pausinystalia yohimbe, Cassia sieberiana and Cissus populnea Roots In Paroxetine-Induced Sexual Dysfunction Male Rats: A Comparative Study:

@#There is a folkloric claim that Pausinystalia yohimbe,Cassia sieberiana and Cissus populnearoots can be used to enhance sexual behaviour in male rats. However, there is still dearth of scientific evidence that substantiated the acclaimed efficacy of separate and combined use of the plant as sex enhancer. Therefore, the aims of this study were to compare the separate and combined effects of aqueous extracts of Pausinystalia yohimbe, Cassia sieberiena and Cissus populnearoots in paroxetine-induced sexually impaired male rats.Thirty five male rats were assigned into seven groups (A-G) such that rats in group A received orally 1.0 ml of distilled water for 7 days, while those in groups B -G which were induced into sexual dysfunction (administration of 10 mg/kg of paroxetine) also received equal volume of distilled water, 7.14 mg/kg body weight of PowmaxM (a reference drug), 50 mg/kg body weight of P. yohimbe, 50 mg/kg body weight of C. sieberiana, 50 mg/kg body weight of C. populneaand 50 mg/kg body weight of 1:1:1 mixture of the three extracts, once daily for seven days respectively. The sexual behavior indices of the male rats and the levels of their reproductive hormones were evaluated by standard procedures. The paroxetine-treatment related reductions (P<0.05) in the sexual behaviour indices of Mount Frequency, Intromission Frequency and Ejaculatory Frequency, levels of serum reproductive hormones of testosterone, luteinizing hormone and follicle stimulating hormone were progressively attenuated by the separate administration of the plant extracts. Furthermore, the increases in the Mount Latency, Intromission Latency, Ejaculatory Latency and Post-ejaculatory Interval were also gradually reduced, following the administration of the plant extracts. The male rat sexual behaviour indices and the levels of the male reproductive hormones following the administration of the 1:1:1 mixture of the extracts were not significantly different (P>0.05) from the effects of the separate extracts. All these changes compared favourably (P>0.05) well with those of the sexual dysfunction rats that received PowmaxM (Group G). The results obtained in the present study indicate that the extracts of these plants may have the potentialfor the management of sexual dysfunction in male rats. The combined use of the plants was not significantly better than the individual use of the plants thereby, each and any of the three plants readily available might be used for this purpose.

Prescripción de paroxetina en adolescentes Colombianos / Prescription of paroxetine in Colombian adolescents

RESUMEN Objetivo Determinar la frecuencia de uso de paroxetina en pacientes adolescentes menores de 20 años afiliados al sistema de salud colombiano. Métodos Estudio de corte transversal, a partir de una base de datos poblacional de personas afiliadas al Sistema General de Seguridad Social en Colombia entre primero de enero 2011 y 31 diciembre 2015 buscando los pacientes menores de 20 años que hubiesen recibido cualquier presentación de paroxetina. Para el análisis de datos se establecieron frecuencias y proporciones. Resultados Se hallaron 777 sujetos prescritos con paroxetina durante los cinco años de evaluación, con edad promedio de 53,8±16, dos años Solo 36 pacientes menores de 20 años lo recibían, especialmente hombres (n=24; 64,8%) con edad media de 17,7±1,8 años. La mayoría estaban siendo tratados en la ciudad de Bogotá (58,3%), seguidos de Medellín (16,7%) y Cartagena (8,3%). Conclusiones Una baja proporción de adolescentes están recibiendo paroxetina en Colombia lo que reduce el riesgo que puede representar este fármaco para ellos.(AU)

ABSTRACT Objective To determine the frequency of paroxetine use in adolescent patients under 20 years of age enrolled in the Colombian Health System. Material and Methods Cross-sectional study, based on a population database of people enrolled in the Colombian Health System between January 1, 2011 and December 31, 2015. The sample included patients under 20 years of age who had received any presentation of paroxetine. For data analysis, frequencies and proportions were established. Results 777 subjects were prescribed with paroxetine during the five years of evaluation, with an average age of 53.8 ± 16.2 years. Only 36 patients under 20 received it, especially men (n=24, 64.8%) with a mean age of 17.7 ± 1.8 years. Most of them were being treated in the city of Bogotá (58.3%), followed by Medellín (16.7%) and Cartagena (8.3%). Conclusions A low proportion of adolescents are receiving paroxetine in Colombia, which reduces the risk that this drug may pose on them.(AU)

Effect of fluoxetine and paroxetine on intestinal motility

Background: Serotonin (5-HT) is a biogenic amine that functions as a neurotransmitter of sensorimotor functions in the digestive tract. Te role of 5-HT agents in the modulation of lower gastrointestinal function. Selective serotonin reuptake inhibitors (SSRIs) are of potential benefit in functional gastrointestinal diseases although formal evidence is lacking. Apart from central effects, they may have peripheral. The present study was carried out to find out the possible effects of fluoxetine and paroxetine on gastrointestinal smooth muscles of rabbit as they cause severe nausea and vomiting initially.Methods: Experimental study design. Power lab (USA) for recording the contractions of ileal smooth muscle of rabbit in response to serotonin, fluoxetine and paroxetine.Results: The percent responses with serotonin, fluoxetine and paroxetine were 100, 10.53, and 4.75 percent respectively.Conclusions: SSRIs (fluoxetine and paroxetine) were unable to enhance the serotonergic transmission in vitro inturn decreases the qualitative response.

MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment

Aberrant expression of microRNAs (miRNAs) has been shown to be involved in early observations of depression. The aim of this study was to determine if serum levels of miRNA-451a, miRNA-34a-5p, and miRNA-221-3p can serve as indicators of disease progression or therapeutic efficacy in depression. We collected data from 84 depressed patients and 78 control volunteers recruited from the medical staff at the West China Hospital. Depression severity was rated using the 24-item Hamilton Depression Scale (HAMD). Serum miRNA-451a, miRNA-34a-5p, and miRNA-221-3p levels were determined in samples from the depressed patients before and 8 weeks after antidepressant treatment as well as in samples from controls. Compared with the controls, the patients had lower miRNA-451a levels, higher miRNA-34a-5p and miRNA-221-3p levels, and increased HAMD scores whether they underwent antidepressant treatment or not. Eight weeks after antidepressant treatment, the patients exhibited increased miRNA-451a levels, decreased miRNA-34a-5p and miRNA-221-3p levels, and reduced HAMD scores. The serum level of miRNA-451a was negatively correlated with HAMD scores of the patients, while the serum levels of miRNA-34a-5p and miRNA-221-3p were positively correlated with HAMD scores whether the patients underwent antidepressant treatment or not. Paroxetine was markedly effective in 50 patients who also displayed an increased level of miRNA-451a but reduced levels of miRNA-34a-5p and miRNA-221-3p. In contrast, paroxetine was moderately effective or ineffective in 34 patients. In conclusion, depressed patients had lower serum miRNA-451a but higher serum miRNA-34a-5p and miRNA-221-3p, and these miRNAs are potential predictors of the efficacy of antidepressants.

Effects of Paroxetine on a Human Ether-a-go-go-related Gene (hERG) K⁺ Channel Expressed in Xenopus Oocytes and on Cardiac Action Potential

K⁺ channels are key components of the primary and secondary basolateral Cl- pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human K⁺ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier K⁺ channel (I(Kr)) in the heart. Mutations in hERG reduce I(Kr) and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at 36℃, treatment with 0.4 µM paroxetine for 5 min decreased the action potential duration at 90% of repolarization (APD₉₀) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

Antidepressant drug paroxetine blocks the open pore of Kv3.1 potassium channel

In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to highfrequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an IC₅₀ value of 9.43 µM and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding (k₊₁) and unbinding (k₋₁) rate constants for the paroxetine effect were 4.5 µM⁻¹s⁻¹ and 35.8 s⁻¹, respectively, yielding a calculated K(D) value of 7.9 µM. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a usedependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.

Comparative study on paroxetine combined with folic acid and paroxetine in the treatment of primary premature ejaculation and plasma 5-HT level / 国际检验医学杂志

Objective To compare the efficacy and safety of paroxetine alone and combined with folic acid in patients complaining of premature ejaculation ,and measured the 5-hydroxyptamine(5-HT ) concentration in two groups before and after treatment and compared the differences .Methods 126 cases of PE were included from department of Urology of 363 Hospital of Chengdu .Subjects were randomly divided into 2 groups ,group A were given paroxetine hydrochloride 20 mg/d ,group B were given paroxetine hydrochloride 20 mg/d and fo-lic acid 0 .4 mg/d ,study duration was 8 weeks .Blood sample got from the candidates both in screening period and after 8 weeks of treatment .The efficiency after treatment was measured by IELT and PEP ,the plasma 5-HT level was measured too .SPSS16 .0 statistical analysis was used .Results After treatment ,IELT of group A and group B was improved from 1 .21 ,1 .18 min to 8 .04 ,9 .42 min .The improvement of average IELT in group B was significantly higher than that in group A ,the difference was statistically significant (P＜0 .05) ;The PEP score and 5-HT level in group B were significantly higher than that in group A ,the difference was statistically significant (P＜0 .05) .Conclusion Paroxetine combined with folic acid in the treatment of primary premature ejaculation has a significant effect ,compared to paroxetine alone .The average plasma level of 5-HT increased significantly ,and folic acid could assist paroxetine in elevating plasma levels of 5-HT and improving primary premature ejaculation symptoms .

Observation of efficacy of quetiapine combined with paroxetine in the treatment of bipolar depression / 中国基层医药

Objective To explore the curative effect of quetiapine combined with paroxetine in the treatment of bipolar depression,and to provide reference for the choice of clinical treatment.Methods According to the digital table,96 patients with bipolar disorder were randomly divided into observation group and control group,48 cases in each group.The control group was treated with quetiapine orally,the observation group was treated with quetiapine combined with paroxetine.After 6 weeks of treatment,the clinical curative effect,the Montgomery Asberg Depression Rating Scale and the Beck pull fan Sen Mania Rating table score before and after treatment were compared between the two groups.At the same time,the adverse reactions of the two groups were compared.Results After 6 weeks of treatment,the total effective rate of the observation group was 70.83％,which was significantly higher than 50.00％ in the control group,the difference was statistically significant(x2 =4.356,P =0.037).After 6 weeks of treatment,the Montgomery Asberg Depression Rating quantity score in the observation group was (14.01 ± 2.95) points,which was significantly lower than (18.07 ± 3.05)points in the control group,the difference was statistically significant (t =5.527,P =0.036).The Baker-pull fan Sen Mania Rating score before and after treatment between the two groups had no statistically significant differences.There were no serious adverse reactions in the two groups.Conclusion Quetiapine combined with paroxetine can effectively inhibit bipolar depressive episodes,avoid manic episodes,has good clinical efficacy and high safety,it is worthy of popularization and application.

Clinical Observation of Acupuncture plus Paroxetine for Depression Due to Liver-qi Stagnation / 上海针灸杂志

Objective To observe the clinical efficacy of acupuncture plus Paroxetine in treating depression due to liver-qi stagnation, for seeking a more effective treatment for this disease.Method Sixty patients with depression due to liver-qi stagnation were randomized into a treatment group and a control group, 30 cases in each group. The treatment group was intervened by acupuncture plus Paroxetine, while the control group was by Paroxetine alone, successively for 8 weeks. Hamilton Depression Scale (HAMD), Chinese medicine syndrome and sign score, and central neurotransmitters were observed before and after the treatment, for evaluating the therapeutic efficacy.Result The total effective rate was 96.6% in the treatment group versus 71.4% in the control group, and the treatment group was superior to the control group (P<0.05).Conclusion Acupuncture plus Paroxetine is an effective method in treating depression due to liver-qi stagnation.

Effects of Paroxetine on Depression Symptom and Neurological Function Recovery of Patients with Post-stroke Depression / 中国药房

OBJECTIVE:To investigate the effects of paroxetine on depression symptoms and neurological function recovery in patients with post-stroke depression. METHODS:A total of 108 patients with post-stroke depression in our hospital were analyzed retrospectively and divided into observation group(51 cases)and control group(50 cases). Both groups received routine therapy as dehydration,activating blood circulation to dissipate blood stasis,anticoagulation,defibringen. Based on it,observation group was additionally given Paroxetine hydrochloride tablet 20 mg,once a day;control group was additionally given Sertraline hydrochloride tablet 50 mg,once a day. Treatment courses of 2 groups lasted for 4 weeks. The depression symptom relief and the recovery of neu-rological function were observed in 2 groups before and after treatment. HAMD score and MESSS score were compared before and after treatment,and the occurrence of ADR was recorded during treatment. RESULTS:Total response rate of depression symptom relief(70.37% vs. 38.89%)and the recovery of neurological function(66.67% vs. 40.74%)in observation group were significant-ly higher than control group,with statistical significance(P0.05);after treatment,HAMD score and MESSS score of 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the control group,with statistical significance(P<0.05). During treatment,no obvious ADR was found in 2 groups. CONCLUSIONS:Paroxetine has good therapeu-tic efficacy for post-stroke depression and can effectively relieve the depression so as to promote the recovery of neurological func-tion,which has a positive effect on the prognosis of patients with acute cerebral infarction and doesn't increase the occurrence of ADR with good safety.

Comparison of Therapeutic Efficacy and Safety of Sertraline and Paroxetine in the Treatment of Post Stroke Depression / 中国药房

OBJECTIVE:To compare the therapeutic efficacy and safety of sertraline and paroxetine in the treatment of post stroke depression.METHODS:The information of 91 patients with post stroke depression were analyzed retrospectively and divided into observation group (42 cases) and control group (49 cases) according to therapy plan.Based on routine treatment,observation group was given Sertraline hydrochloride tablet orally with initial dose of 50 mg at first week,once a day,increasing by 50 mg each week,no more than 200 mg.Control group was given Paroxetine tablet with initial dose of 10 mg,once a day,increasing by 10 mg each week,no more than 40 mg.Treatment course of 2 groups lasted for 2 months.Clinical efficacies of 2 groups were observed.NIHSS score,MMSE score,HAMD score,the serum levels of 5-HT,BDNF and S1003 were observed before and after treatment,and the correlation of serum levels of 5-HT,BDNF and S100β with HAMD score were evaluated in observation group after treatment;the occurrence of ADR was recorded.RESULTS:The total response rate of observation group (90.48％) was significantly higher than that of control group (73.47％),with statistical significance (P＜0.05).After treatment,NIHSS score,HAMD score and S100β level of 2 groups were significantly lower than before treatment,and HAMD score and S100β level of observation group were significantly lower than those of control group.MMSE score,serum levels of 5-HT and BDNF in 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group,with statistical significance (P＜0.05).There was no statistical significance in NIHSS score between 2 groups (P＞0.05).The serum levels of 5-HT and BDNF were negatively correlated with HAMD score in observation group after treatment,and the level of S100β was positively correlated with HAMD score.There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Based on routine treatment,therapeutic efficacy of sertraline is significantly better than that of paroxetine in the treatment of post stroke depression,and can improve cognitive function and depression.The two drugs are similar in improving nerve function and mental state,safety.