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Objective:To investigate the efficacy of tandospirone combined with venlafaxine in the treatment of comorbid anxiety and depression and its effects on neurotransmitters and related factors.Methods:A total of 92 patients with comorbid anxiety and depression who received treatment in the Second People's Hospital of Lishui between June 2019 and June 2020 were included in this study. They were randomly divided into an observation group and a control group ( n = 46/group). The control group was treated with venlafaxine, while the observation group was treated with tandospirone and venlafaxine. Before and after treatment, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), the levels of 5-hydroxytryptamine, brain-derived neurotrophic factor, nerve growth factor, and adverse drug reactions were compared between the two groups. Results:At 4 and 8 weeks after treatment, HAMA scores in the observation group were (11.39 ± 3.11) points and (8.26 ± 2.18) points, respectively, which were significantly lower than (14.72 ± 3.57) points and (10.46 ± 2.37) points in the control group ( t = 4.77, 4.63, both P < 0.05). At 4 and 8 weeks after treatment, HAMD scores in the observation group were (15.95 ± 2.90) points and (9.33 ± 1.54) points, respectively, which were significantly lower than (17.43 ± 2.87) points and (13.28 ± 2.65) points in the control group ( t = 2.46, 8.74, both P < 0.05). After treatment, 5-hydroxytryptamine, nerve growth factor, and brain-derived neurotrophic factor levels in the observation group were (154.59 ± 45.26) μg/L, (13.62 ± 1.16) ng/L, (28.54 ± 2.33) ng/L, respectively, which were significantly higher than (129.99 ± 48.31) μg/L, (11.98 ± 1.04) ng/L, and (25.69 ± 2.51) ng/L in the control group ( t = 2.52, 7.14, 5.64, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( χ2 = 0.81, P = 0.369). Conclusion:The adjuvant treatment with tandospirone can markedly improve anxiety and depression and protect neurological function of patients with comorbid anxiety and depression, and is highly safe.
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Venlafaxine (VEN) is a new antidepressant drug that can effectively antagonize the reuptake of serotonin (5-HT) and norepinephrine (NE), compared with other antidepressants, venlafaxine pharmacokinetics / pharmacodynamics (PK-PD) is more regular and has the characteristics of less toxic side effects, fast oral absorption, and high bio-availability. This article reviews the PK-PD model-ling of venlafaxine and its quantitative relationship, as well as the factors affecting the process in vivo of venlafaxine, including sex, body weight, individual genotype, liver and kidney function impairment, drug-drug interaction and other related factors.
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OBJECTIVE To study the pharm acokinetics of venlafaxine（VEN）combined with vinpocetine （VIN）in rats ，and to investigate the interaction between them. METHODS Healthy male SD rats were randomly divided into VEN group （13.5 mg/kg）， VIN group （1.8 mg/kg） and VEN + VIN group （13.5 mg/kg VEN + 1.8 mg/kg VIN ），with 6 rats in each group. Before administration，rats in each group fasted but didn ’t deprived of water for 12 hours，and were given corresponding drugs intragastrically at one time. Blood was collected from rats in each group through orbital venous plexus at different time points after administration. After plasma sample was pretreated （domperidone as internal standard ），LC-MS/MS method was adopted to determine the concentration of VEN ，active metabolite O-desmethylvenlafaxine of VEN （ODV）and active metabolite apovinblastic acid of VIN （AVA）in plasma. DAS 2.0 software was used to calculate and compare the pharmacokinetic parameters of VEN ，ODV and AVA. RESULTS Compared with VEN group ，the pharmacokinetic parameters cmax，AUC0－t，AUC0－∞，MRT0－t（except for VEN），MRT0－∞（except for VEN ）of VEN and ODV in VEN+VIN group were increased significantly ，while CL/ F and Vz/F were decreased significantly （P＜0.05 or P＜0.01）. Compared with VIN group ，there was no statistical difference in the pharmacokinetic parameters of AVA in rat plasma of VEN+VIN group （P＞0.05）. CONCLUSIONS After the combination of VEN and VIN ，VIN can affect the metabolism of VEN by increasing the absorption of VEN and ODV and slowing down their elimination.
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Objective:To investigate the efficacy of venlafaxine combined with transcranial direct current stimulation in the treatment of postpartum depression and its effects on neurological function.Methods:A total of 135 patients with postpartum depression who were admitted to Wenzhou Seventh People's Hospital from November 2019 to October 2021 were included in this study. They were randomly divided into observation ( n = 70) and control ( n = 65) groups. The control group was treated with venlafaxine alone, and the observation group was treated with an IS200 intelligent electrical stimulator based on the treatment used in the control group. The two groups were treated for 4 weeks. Clinical efficacy and neurological function were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group (98.57% vs. 89.23%, χ2 = 7.61, P < 0.05). After treatment, the scores of Edinburgh Postnatal Depression Scale and Hamilton Depression Scale in the observation group were (8.03 ± 0.79) points and (9.03 ± 3.98) points, respectively, which were significantly lower than (11.74 ± 0.98) points and (14.68 ± 3.79) points in the control group ( t = 3.28, 4.65, both P < 0.05). Standard deviation of heart rate variability, root mean square of successive differences between adjacent NN intervals, ratio of low frequency to high frequency, activity of the autonomic nervous system in the observation group were (32.38 ± 0.93) ms, (27.86 ± 0.78) ms, 1.79 ± 0.19, (86.65 ± 1.21) points, respectively, which were significantly higher than (27.84 ± 0.88) ms, (25.79 ± 0.81) ms, 1.38 ± 0.14, (82.94 ± 1.19) points in the control group ( t = 4.09, 3.72, 2.98, 4.09, all P < 0.05). Conclusion:Venlafaxine combined with transcranial direct current stimulation for treatment of postpartum depression can enhance clinical efficacy and remarkably improve patient's neurological function.
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Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence, open-label, two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method, and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows: Cmax(58.50±19.47)vs(60.14±22.18)μg•L-1, AUC0-t(1 074.1±526.7)vs(1 057.9±539.7)μg•h•L-1, AUC0-∞(1 084.7±536.8)vs(1 067.8±554.0)μ g•h•L-1.The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows: Cmax(101.63±29.64)vs(101.45±31.62)μg•L-1, AUC0-t(2 694.0±834.5)vs(2 702.9±946.4)μg• h•L-1, AUC0-∞(2 753.9±885.5)vs(2 753.2±988.4)μg•h•L-1.The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ for the test preparation and the reference preparationwere all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.
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ObjectiveTo investigate the efficacy and safety of venlafaxine in the treatment of depression under the guidance of pharmacogenomics testing， and to provide references for individualized medication. MethodsA total of 66 patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for depressive episode were included in the study. Patients who were recommended to be treated with venlafaxine in the pharmacogenomics testing report were divided into study group （n=32）， and those who were decided to be treated with venlafaxine by doctors after consultation with patients were divided into control group （n=34）. At the baseline and the end of the 2nd， 4th， 6th and 8th weekend of treatment， Hamilton Depression Scale-24 item （HAMD-24） was adopted to evaluate the clinical efficacy. Meanwhile， Sheehan Disability Scale （SDS） was applied to measure the social function of patients at the baseline and the end of the 8th weekend of treatment. After treatment， Treatment Emergent Symptom Scale （TESS） was used to assess the incidence of adverse reactions. ResultsAt the end of the 4th， 6th and 8th weekend of treatment， HAMD-24 scores in the study group were all lower than those in the control group， with statistical differences （t=2.344， 4.316， 5.760， P<0.05 or 0.01）. At the end of the 8th weekend of treatment， SDS score of the study group was lower than that of the control group， with statistical difference （t=2.173， P<0.05）. The adverse reaction rate in the study group was lower than that in the control group， with statistical difference （χ2=5.720， P<0.05）. ConclusionTreatment of depression with venlafaxine based on pharmacogenetic testing is an effective and safe way to alleviate the depression symptoms in patients.
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The current research work was to develop bilayer tablet of venlafaxine hydrochloride to increase drug efficacy for efficient treatment of depression. The satisfactory result of treatment can be achieved upon the maintenance of drug concentration within an effective level in the body, so a uniform and constant drug supply are desirable. An immediate layer of venlafaxine HCl was formulated using super disintegrants, i.e., croscarmellose sodium (CCS) and sodium starch glycolate (SSG); tablet compact by direct compression. HPMC K100M and ethylcellulose (EC) were utilized as release retarding polymers in sustained release layer by wet granulation technique with the help of PVP K30 in IPA solution (10%) as a granulating agent. Full 32 factorial designs were used to find out the optimum quantity of release retardant polymers. Bilayer tablet was evaluated for various parameters, i.e. hardness, friability, weight variation, % drug content, disintegration time (IR layer), and % drug release study. Statically, an analysis was carried out using factor X1 (HPMC K100M) and X2 (EC) for dependent variable % drug release at 8, 12, and 20 hours. A formulation was optimized and a formulation containing 305.36 mg of HPMC K100M and 54.03 mg of ethyl cellulose. Optimized formulation show 47.12 ± 2.1, 59.89 ± 2.2, and 89.06 ± 2.3 drug release at 8, 12, and 20 hours, respectively, which is almost similar to theoretical dose calculation with similarity factor f2 97, 99, and 98%, respectively. Bilayer tablet formulation was observed to be stable and fulfilled all compendia specifications.
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Abstract Introduction Depression is a global health problem with nearly 350 million people affected, mainly women. However, nowadays a rising amount of men are being diagnosed. This makes necessary the screening of new treatment options that are effective in women as well as in men. Objective To analyze if the administration of mirtazapine and venlafaxine to male and female rats shows a sex-related antidepressant-like effect, and the possible associated neurochemical mechanisms. Method Mirtazapine (40 mg/kg) or venlafaxine (60 mg/kg) were administered subchronically to young adult male and female (ovariectomized and steroid-primed) rats, and their antidepressant-like effects were evaluated using the forced swim test (FST). The active behaviors, swimming and climbing, were also analyzed. Results a) mirtazapine and venlafaxine reduced immobility in the FST in males and females; b) both antidepressants increased climbing and swimming in male rats; c) in female rats, mirtazapine and venlafaxine only increased swimming. Discussion and conclusion In males, the effects of mirtazapine and venlafaxine seem to be produced by the activation of the serotonergic and noradrenergic systems. Conversely, estradiol might be modulating the mechanisms of action of both antidepressants in females producing only an increased swimming and suggesting the participation of the serotonergic system.
Resumen Introducción La depresión es un trastorno psiquiátrico que representa un problema de salud mundial. Afecta a cerca de 350 millones de personas, predominantemente mujeres. Sin embargo, algunos reportes indican que su incidencia en hombres está aumentando, por lo que es necesario buscar opciones de tratamiento que sean igualmente efectivas en ambos sexos. Objetivo Analizar si existen diferencias relacionadas con el sexo en el efecto de tipo antidepresivo de la mirtazapina y la venlafaxina, y considerar los posibles mecanismos neuroquímicos involucrados. Método se administraron mirtazapina (40 mg/kg) o venlafaxina (60 mg/kg) en esquema subcrónico a grupos independientes de ratas macho y hembra ovariectomizadas tratadas con estradiol y progesterona. Se evaluaron el efecto tipo antidepresivo y las conductas activas (nado y escalamiento) utilizando la prueba de nado forzado (PNF). Resultados a) tanto la mirtazapina como la venlafaxina redujeron la inmovilidad en la PNF en machos y hembras; b) ambos antidepresivos incrementaron las conductas activas en machos; c) en hembras, la mirtazapina y la venlafaxina produjeron un aumento del nado, pero no modificaron el escalamiento. Discusión y conclusión En machos, los efectos de la mirtazapina y la venlafaxina en la PNF se deben a su acción sobre los sistemas serotonérgico y noradrenérgico; en cambio, en hembras sólo se modifica la conducta de nado, lo que sugiere que el estradiol modula las acciones de ambos antidepresivos sobre el sistema serotoninérgico.
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A reverse phase high performance liquid chromatography method has been developed and validated for accelerated stability study and determination of pharmacokinetic parameters of venlafaxine HCl. The chromatographic separation was carried out using ODS analytical column (250 × 4.6 mm i.d., 5 µm particle size). The mobile phase included acetonitrile, methanol and potassium dihydrogen phosphate buffer (30:30:40; pH 6.1) at a flow rate 1.5 mL min−1. UV-Visible detector was used at wavelength of 227 nm to monitor elutions. Retention time observed was 2.745 min. The method was validated for linearity, accuracy, precision, sensitivity and robustness. Accelerated stability study of venlafaxine HCl capsules was carried out at 40 and 50 ºC under 75% RH level. Suggested method was successfully applied for the pharmacokinetic analysis of venlafaxine hydrochloride tablets. Each of ten albino rabbits (≈ 1.2 kg each) was orally administered with 5 mg dose of venlafaxine HCl. The method was proved to be linear (R2 >0.998), accurate (98.25-99.27%), sensitive (LOD: 35ngmL−1; LOQ: 105 ng mL−1) and robust (RSD<1%). The drug showed stability at accelerated conditions of temperature and humidity. The main pharmacokinetic parameters of tested products were as follows: tmax was 2.5h, Cmax was 56.5 µg mL−1, t1/2 was 8.2 h, AUC0-36 was 845.9 µg h mL−1. The developed method is suitable to apply for quality control analysis and pharmacokinetic studies.
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Background: Pain is an unpleasant sensation with varying subjective experience. Its management is always challenging for physicians particularly in case of chronic pain. Chronic pain and depression usually co-exist due to poor quality of life and increase in health care costs posing an individual to suffer from depression. Anti-depressants for pain management are being used successfully using since years. In this study venlafaxine, a newer anti-depressant drug was evaluated for anti-nociceptive activity, tail immersion test an analgesic animal model of albino mice.Methods: Randomly selected albino mice of either sex with reaction time of <6 seconds were included in the study and divided into 7 groups with 6 mice in each group. Grouping was done based on the drug received i.e., venlafaxine 15, 30 and 60 mg/kg, tramadol 10 and 20 mg/kg, control group (normal saline) and combination group venlafaxine 15 mg/kg+tramadol 10 mg/kg. Drugs were administered by intra-peritoneal route.Results: Venlafaxine (30 and 60 mg/kg), tramadol (20 mg/kg) and combination group venlafaxine (15 mg/kg+tramadol 10 mg/kg) has shown significant (p<0.001) increase in tail withdrawal latency compared to control group (normal saline) by tail immersion test. Venlafaxine potentiated anti-nociceptive activity of tramadol on concomitant administration with tramadol. Venlafaxine at 60 mg/kg has comparable anti-nociceptive effect to tramadol at 20 mg/kg.Conclusions: Venlafaxine at doses of 30 and 60 mg/kg is having anti-nociceptive effect, but less potent than tramadol.
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Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.
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Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Saphenous Vein/drug effects , Saphenous Vein/transplantation , Tranylcypromine/pharmacology , Fluoxetine/pharmacology , Amitriptyline/pharmacology , Antidepressive Agents/pharmacology , Reference Values , Vasodilation/drug effects , Endothelium, Vascular/drug effects , Coronary Artery Bypass/methods , Analysis of Variance , Transplants/drug effects , Venlafaxine Hydrochloride/pharmacology , Muscle, Smooth, Vascular/drug effectsРеферат
OBJECTIVE@#To explore the effectiveness and safety of the combined treatment with acupuncture and venlafaxine hydrochloride on depression in terms of the microstructure change of white matter fiber tracts of brain based on diffusion tensor imaging technology (DTI).@*METHODS@#The prospective study design was adopted. All of 60 patients with depression were randomized into an acupuncture-medication group and a medication group, 30 cases in each one. In the medication group, venlafaxine hydrochloride was used, 75 mg per day in the 1st week, 150 mg per day in the 2nd week and 225 mg per day from the 3rd to 6th week. In the acupuncture-medication group, on the base of the treatment in the medication group, acupuncture was combined. Baihui (GV 20) and Yintang (GV 29) were the main acupoints. The supplementary acupoints were selected according to the clinical symptoms of individuals. The needles were retained for 30 min. Acupuncture was provided once every 2 days, 3 times a week. The consecutive 12 weeks of treatment were required in the two groups. Additionally, a normal group was prepared with 30 healthy volunteers. Separately, before treatment, in 2, 8 and 12 weeks of treatment, Hamilton's depression scale (HAMD-17), Beck depression inventory scale (BDI) and the antidepressant side effect scale (SERS) were adopted to evaluate the effectiveness and safety of the two groups. Moreover, before and after 12 weeks of treatment, DTI was adopted to detect the fractional anisotropy score (FA) of each brain region in the patients.@*RESULTS@#After treatment, the scores of HAMD-17 and BDI were all reduced in the two groups (0.05). Compared with the healthy volunteers, FA scores in 6 brain regions changed obviously in the patients with depression, including the white matter of bilateral frontal lobes, splenium of corpus callosum, left cingulated gyrus, white matter of bilateral inferior temporal gyrus, white matter of bilateral inferior parietal lobe and white matter of bilateral deep temporal occipital region separately. Before treatment, the differences in FA scores of these 6 brain regions were not significant statistically between the two groups (>0.05). After treatment, FA scores in the white matter of bilateral frontal lobes, white matter of bilateral inferior temporal gyrus and white matter of bilateral deep temporal occipital region in the acupuncture-medication group were all higher than those in the medication group (<0.05).@*CONCLUSION@#Acupuncture repairs the brain white matter fiber tracts in some brain regions to certain extent and the therapeutic effects are enhanced with the adjuvant medication of venlafaxine hydrochloride.
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Humans , Acupuncture Therapy , Brain , Depression , Therapeutics , Diffusion Tensor Imaging , Prospective Studies , Venlafaxine HydrochlorideРеферат
Objective To investigate the effect of psychological intervention combined with venlafaxine and risperidone in the treatment of refractory depression and its influence on the quality of life .Methods 97 patients with refractory depression were selected .According to the random number table , they were divided into the observation group(50 cases) and the control group(47 cases).The control group was given venlafaxine combined with risperidone treatment,the observation group received psychological intervention on basis of the control group .The Hamilton depression scale ( HAMD) of patients in the two groups before treatment ,4,8 and 12 weeks after treatment were recorded .The curative effect after 12 weeks of treatment was evaluated ,the adverse reaction was evaluated by the side effects scale ( TESS ) , and the quality of life ( WHOQOL-100 ) of the two groups before treatment , 12 weeks after treatment were compared .Results The HAMD score of the two groups had no statistically significant difference before treatment(t=0.307,P>0.05).After treatment for 4,8,12 weeks,the HAMD scores of the two groups were significantly lower than before treatment (t=5.743,17.756,27.288,4.595,15.801,23.247,all P<0.05),and the HAMD scores in the observation group after treatment for 8 weeks and 12 weeks were significantly lower than those in the control group(t=0.887,3.717,5.854,all P<0.05).After 12 weeks of treatment,the total effective rate of the observation group was significantly higher than that of the control group (90.00％ vs.74.47％,χ2 =4.043,P <0.05 ).There was no statistically significant difference in incidence rate of adverse reactions between the two groups (26.00％vs.25.52％,χ2 =0.003,P >0.05).The WHOQOL-100 scores of the two groups had no statistically significant differences before treatment(t=0.597,0.497,0.378,0.923,0.136,all P>0.05).The WHOQOL-100 scores of the two groups after treatment were significantly higher than those before treatment ( t =11.668,8.701, 6.857,7.053,2.247,4.815,4.639,2.999,4.117,2.011,all P<0.05).After treatment,the psychological and physiological independence and social relationship domain scores in the observation group were significantly higher than those in the control group(t=5.618,3.295,4.335,3.603,all P<0.05).Conclusion Psychological interven-tion combined with venlafaxine and risperidone in the treatment of refractory depression can significantly improve the clinical efficacy ,improve the clinical symptoms and the quality of life of patients .
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Objective To investigate the clinical effect of sodium valproate tablets combined with venlafaxine hydrochloride sustained-release tablets in female patients with schizophrenia complicated with affective disorders and its influence on the recurrence time.Methods From January 2013 to July 2016,98 female patients with schizophrenia complicated by affective disorder in Taiyuan Mental Hospital were selected and randomly divided into single group (n =49) and combination group (n =49) according to the digital table.The single drug group was treated with sodium valproate tablets,and the combination group was treated with venlafaxine hydrochloride sustained-release tablets on the basis of a single drug group.The clinical efficacy and recurrence time of the two groups were compared.Results The scores of withdrawal symptoms [(4.39 ± 0.94) points],positive symptoms [(11.55 ± 4.30) points],negative symptoms [(11.09 ± 1.21) points] and psychiatric symptoms [(12.01 ±2.16) points] in the combination group were all significantly lower than those at 1 month after treatment[(10.98 ±1.43) points,(16.74 ± 3.89) points,(18.43 ± 2.05) points,(19.83 ± 3.44) points] (t =12.957,18.471,all P ＜0.05).The incubation period and amplitude of the P300 potentials in the combination group were (314.55 ± 9.21) s,(4.05 ± 1.76)s,respectively,which were both higher than those of the single drug group [(341.60 ± 25.87)s,(2.58 ± 2.30)s] (t =18.251,15.738,all P ＜ 0.05).The eye movements of the combination group 12 weeks after operaion were (27.30 ± 1.41) s and (6.15 ± 0.98) s,respectively,which were higher than those of the single drug group[(25.10 ± 2.93) s and (5.10 ± 1.20) s] (t =13.992,15.836,all P ＜ 0.05).The recurrence rate of the combined group was 8.16％,which was lower than 18.37％ of the single drug group(x2 =6.893,P ＜ 0.05).The hospitalization duration [(14.83 ± 4.61)d],symptom improvement time [(34.94 ± 7.85)d] of the combined group were shorter than those of the single drug group [(27.91 ± 7.49) d,(59.81 ± 10.94) d] (t =18.946,21.461,all P ＜ 0.05).The recurrence time at 12 weeks after treatment of the combination group was (148.48 ± 33.19)d,which was longer than (109.46 ±28.88)d of the single drug group(t =16.893,P ＜0.05).Conclusion The combination of sodium valproate tablets and venlafaxine hydrochloride sustained-release tablets in.patients with schizophrenia complicated with affective disorders can improve the clinical effect,shorten the recurrence time and improve the cognitive function of patients,which is worth popularizing and applying.
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OBJECTIVE:To develop a method for simultaneous determination of carbamazepine,venlafaxine,rosiglitazone and nifedipine in human plasma.METHODS:UPLC-MS/MS method was adopted to determine plasma sample after precipitated with methanol (containing 0.1％ formic acid) using pioglitazone hydrochloride as internal standard.The determination was performed on Waters ACQUITY UPLC HSS C18 column with mobile phase consisted of aqueous solution containing 0.01％ formic acid-methanol containing 0.01％ formic acid (gradient elution) at the flow rate of 0.3 mL/min.The column temperature was 50 ℃,and sample size was 5 μL.ESI was used for positive ion scanning by multi reaction monitoring mode.The ion pairs for quantitative analysis were m/z 237.00 to 194.05 (carbamazepine),m/z 278.20 to 58.10 (venlafaxine),m/z 358.08 to 135.04 (rosiglitazone),m/z 347.15 to 315.17 (nifedipine),m/z 357.09 to 134.06 (internal standard).RESULTS:The liner ranges of carbamazepine,venlafaxine hydrochloride,rosiglitazone hydrochloride and nifedipine were 2.00-2 000.00 (r=0.995 9,n=5),2.12-2 120.00(r=0.990 5,n=5),2.00-2 000.00(r=0.991 5,n=5) and 2.04-1 020.00(r=0.991 0,n=5) ng/mL;the minimum detection limits were 0.200,0.106,0.100,1.020 ng/mL,respectively.RSDs of inter-day and intra-day were less than 15％.The absolute values of RE were less than 15％.The extraction recoveries were 65.66％-96.36％ (RSD％ ＜15％,n=5),and matrix effects ranged 80.99％-114.33％.The plasma concentrations of carbamazepine in 2 epileptic patients were (1 500.41 ± 169.11),(1 159.01 ±59.24) ng/mL(RSD were 11.27％,5.60％,n=3).The plasma concentrations of nifedipine in 2 hypertensive patients were (14.68 ±1.92),(21.18 ± 3.59)ng/mL (RSD were 16.98％,13.10％,n=3).CONCLUSIONS:The method is simple,specific,sensitive,accurate and suitable for the monitoring of plasma concentration and pharmacodynamic study of above drugs.
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OBJECTIVE:To establish a method for simultaneous determination of methadone,venlafaxine and their metabolites in rat plasma,and to use it for the study of pharmacokinetic in rats. METHODS:UPLC-MS/MS method was adopted to determine plasma after precipitated with acetonitrile using diazepam as internal standard. The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile-0.1％ formic acid (gradient elution) at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃,and sample size was 2 μL. ESI was used for positive ion scanning by multiple reaction monitoring (MRM) mode. The ion pairs for quantitative analysis were m/z 310.4→265.4(methadone),m/z 278.2→234.1 (EDDP),m/z 278.1→57.8(venlafaxine),m/z 263.9→57.9(O-desvenlafaxine),m/z 285.1→193.1(internal standard). Eight SD rats were given methadone hydrochloride 6 mg/kg and venlafaxine hydrochloride 10 mg/kg intragastrically(4 rats for each drug);blood samples (0.3 mL) were collected from the tail vein before and 0.083,0.167,0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12, and 24 h after medication. Pharmacokinetic parameters were calculated by using DAS 3.0 software. RESULTS:The linear ranges of methadone,EDDP,venlafaxine and O-desvenlafaxine were 0.5-250 ng/mL(r=0.9997),0.5-250 ng/mL(r=0.9992),0.4-200 ng/mL(r=0.9999),0.4-200 ng/mL(r=0.9999),respectively. The limits of quantitation were 0.5,0.5,0.4,0.4 ng/mL. RSDs of intra-day and inter-day were all lower than 9.0％(n=6). The method recoveries were 94.20％-102.87％,90.93％- 102.94％, 92.95％-101.61％,90.33％-101.97％(RSD≤5.5％,n=6). The extraction recoveries were 85.90％-94.45％,85.97％- 91.66％, 87.97％ -93.58％ , 88.53％ -94.54％(RSD≤5.9％ ,n=6). The matrix effects were 95.96％ -97.78％ , 92.33％ -97.40％ , 95.28％-97.71％,95.33％-95.74％(RSD≤4.9％,n=3). The pharmacokinetic parameters included that t1/2 were (1.42 ± 1.02),(2.59 ± 0.76),(0.63 ± 0.08),(1.29 ± 0.14) h;cmax were (52.21 ± 5.42),(25.68 ± 3.45),(45.68 ± 2.29),(47.63 ± 13.09) μg/L;MRT0-24 h were (3.55 ± 0.21),(3.98 ± 0.41),(1.44 ± 0.21),(2.01 ± 0.17) h;AUC0-24 h were (201.95 ± 51.14),(86.092 ± 15.95),(75.38 ± 23.95),(82.90 ± 23.44)μg·h/L. CONCLUSIONS:The method is specific, absolute separated, rapid and sensitive, and can be used for the simultaneous determination of methadone,venlafaxine and their metabolites in plasma and pharmacokinetics research.
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Aim To investigate the effects of chronic corticos-terone injection on anxiety and depression-like behavior of tree shrews, evaluate the predictability of drug and establish a novel animal model of anxious depression .Methods Twelve Chinese and Burma tree shrews were randomly divided into normal group, model group and venlafaxine group .The anxious depres-sion model of tree shrew was established by chronic corticoster-one injection ( ih, 27 mg· kg-1 , 21 d) .The venlafaxine group received intragastric administration (6 mg· kg-1).Autonomous activity score, sugar water preference test and Morris water maze test were used to evaluate the anxiety and depression-like behav-ior of tree shrews .The expressions of CRH , ACTH and COR in the tree shrew plasma were determined by Elisa kit .The con-tents of monoamine neurotransmitters of tree shrews in the hippo-campus , amygdala and prefrontal cortex were detected by HPLC-ECD.Results Compared with the normal group , the autono-mous activity score , sugar water partial eclipse degree and the learning and memory ability significantly decreased (P<0.01), while the contents of CRH , ACTH and COR significantly in-creased ( P<0.05) , and the contents of 5-HT, NE and DA in the hippocampus , amygdala and prefrontal cortex declined in the model group(P<0.05).In the venlafaxine group, the learning and memory abilities of the tree shrews were improved , the lev-els of CRH and COR in plasma were significantly decreased ( P<0.05), and the contents of 5-HT, NE and DA were increased (P<0.05).Conclusions The tree shrews of anxious depres-sion have obvious HPA axis hyperactivity and monoamine neuro-transmitter disorder , and venlafaxine can reverse this phenome-non, indicating that the tree shrews model of anxious depression has drug predictability , which is a kind of novel animal model of anxious depression closer to human in clinic .
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Venlafaxine is a serotonergic and noradrenergic reuptake inhibitor which is used for the treatment of depression. We report a case of galactorrhea in a patient with major depressive disorder after starting treatment with venlafaxine. In particular, we discuss the course of hyper and normoprolactinemic galactorrhea. We managed this side effect initially by dose reduction and further by switching to essitalopram. Physicians should be aware of endocrinologic side effects such as galactorrhea during the serotonin and noradrenaline reuptake inhibitor treatment.
Тема - темы
Female , Humans , Pregnancy , Depression , Depressive Disorder, Major , Galactorrhea , Norepinephrine , Prolactin , Serotonin , Venlafaxine HydrochlorideРеферат
Objective To investigate the effect and safety of venlafaxine augmented with amisulpride in the treatment of major depressive disorder. Methods Fifty patients with major depressive disorder were randomly divided into control group treated with venlafaxine (n=25) and study group treated by venlafaxine augmented with amisulpride (n=25). The treatment lasted 8 weeks. Hamilton Depression Rating Scale (HAMD) and Treatment Emergent Symptom Scale (TESS) were used to evaluate the effect and safety of therapy before and 1, 2, 4, and 8-week after treatment. The serum level of IL-18 was detected at each time points in two groups. Results After treatment for 2, 4 and 8 weeks, the serum levels of IL-18 were significantly decreased in study group than that of control group (P<0.05). The serum levels of IL-18 were gradually reduced with the extended treatment time in two groups. There was no interaction between two groups and different processing times. Scores of HAMD decreased gradually after treatment in two groups. Scores of HAMD were significantly lower after treatment than that before treatment in study group (P<0.05). Scores of HAMD were significantly lower after treatment than that before treatment except for one-week treatment in control group (P<0.05). There were no significant differences in HAMD scores before treatment and one-week treatment of two groups. Scores of HAMD were significantly lower 2,4 and 8 weeks after treatment in study group compared with those of control group (P<0.05). There was a interaction between groups and processing times (P<0.05). The effective rates increased in study group (96%) than control group (76.0%). The adverse effects were less in two groups. Conclusion The low dose of amisulpride helps to improve the efficacy of venlafaxine in the treatment of major depressive disorder, which has good security and can inhibit inflammatory reaction.
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Objective To observe the effect of modified electroconvulsive therapy combined with venlafaxine on cognitive function and its efficacy in patients with depression.Methods 60 patients with depressive disorder were selected,and they were randomly divided into study group and control group according to the random number table method,30 cases in each group.The patients in the study group accepted modified electroconvulsive therapy for 10 times combined with venlafaxine sustained-release tablets treatment,while the patients in the control group were only treated with venlafaxine.Both two groups were treated for 6 weeks.The cognitive function was assessed by the Repeat able Battery for the Assessment of Neuropsycholgical Status (RBANS) and the therapeutic effect was evaluated by Hamilton Depression(HAMD) Scale before and after treatment.Results The scores of immediate memory,delayed memory,speech function,visual breadth and attention of both two groups after treatment were significantly higher than those before treatment(all P ＜ 0.05),and the attention score of the study group was (109.96 ± 19.01) points,which was higher than (100.32 ± 17.13)points of the control group (t =2.062,P ＜ 0.05).The HAMD scores after treatment in both two groups were significantly lower compared with those before treatment (all P ＜ 0.05),and the HAMD score of the study group was (7.23 ± 4.19)points,which was lower than (10.27 ± 5.99)points of the control group (t =2.273,P ＜ 0.05).The total effective rate of the study group(96.7％) was significantly higher than that of the control group (86.7 ％) (x2 =6.546,P ＜ 0.05),and the cure rate of the study group (60.0％) was also higher than that of the control group (36.7％) (x2 =10.901,P ＜ 0.05).Conclusion Modified electroconvulsive therapy combined with venlafaxine treatment can effectively improve the cognitive function of depressive patients,and its effect is significantly better than monotherapy.