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1.
Barak Y Swartz M Baruch Y 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(7):1744-1747
Background
Approximately 50% of patients with major depressive disorder (MDD) do not respond after adequate first-line treatment with a selective serotonin reuptake inhibitor (SSRI). Special interest is paid to whether specialist level inpatient psychiatric care results differ from community studies.Aim
To compare switching alternatives after treatment failure with an SSRI; switching to venlafaxine (Dexcel Pharma Israel) versus switching to another SSRI in depressed inpatients.Method
A retrospective register study of inpatients was undertaken in a psychiatric tertiary care university center serving an urban catchment area in Israel with a population of more than 900,000.Results
A total of 401 MDD inpatients were assigned to antidepressant treatment. Of these, 232 records (47 venlafaxine, 185 SSRI) were included in the analysis. Patients assigned to venlafaxine treatment were older (mean age 64.3 ± 15 years versus 53.6 ± 17; p < 0.01) and had more comorbid physical disorders (80% versus 57%; p < 0.001).In the primary analysis, there was no statistical difference between groups in reduction in CGI-S total scores. The secondary end point of achieving a CGI-S score of 2 or less (1 = normal, not at all ill or 2 = borderline mentally ill) was statistically significantly better for the venlafaxine treated inpatients (P = 0.02). AEs were reported less than 10% of patients in both groups.Conclusion
Patients who remain severely depressed following treatment with an SSRI may gain benefit from the dual-action drug venlafaxine, rather than switching to another SSRI. These findings need to be further supported by prospective studies. 相似文献2.
Reiji Yoshimura Hikaru HoriAtsuko Ikenouchi-Sugita Wakako Umene-NakanoNobuhisa Ueda Jun Nakamura 《Progress in neuro-psychopharmacology & biological psychiatry》2009
In the present study, we compared plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNFα), and brain-derived neurotrophic factor (BDNF) among selective serotonin reuptake inhibitor (SSRI)- or serotonin noradrenaline reuptake inhibitor (SNRI)-responsive depressed patients (n = 31), SSRI- or SNRI-refractory depressed patients (n = 20), and healthy controls (n = 30). The plasma levels of IL-6 and TNF-α were significantly higher in depressed patients than in healthy controls. Treatment with antidepressants significantly reduced plasma levels of IL-6 and TNF-α. In addition, the plasma IL-6 level, but not the plasma TNF-α level, was higher in SSRI-refractory than SSRI-responsive depressed patients, and higher in SNRI-refractory than SNRI-responsive depressed patients. On the other hand, the plasma BDNF level was significantly lower in depressed patients than in healthy controls, whereas no difference was found in plasma BDNF levels between SSRI-responsive and -refractory depressed patients or between SNRI-responsive and -refractory depressed patients. These results suggest that higher plasma IL-6 activity is associated with the refractoriness of depression, and plasma IL-6 levels might be a predictor for response to SSRIs or SNRI. 相似文献
3.
Anne Flöck Astrid Zobel Gerhard Bauriedel Christoph Hammerstingl Anna Schuhmacher Georg Nickenig 《Thrombosis research》2010,126(2):e83
Introduction
Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation.Methods
Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting. Depressed patients were randomized to two groups treated either with escitalopram (n = 47) or nortriptyline (n = 44). Platelet aggregation was studied on days 0, 1, 3, 7, 14, 21, 84 of continuing medication and was determined in response to adenosine diphosphate (ADP) and collagen.Results
Platelet aggregation induced by ADP was increased among depressive patients compared with that of healthy controls (26%, p = 0.006). With antidepressant treatment, changes in platelet aggregation remained comparable in both groups at early time points (d1 to 21). In contrast, at day 84, patients with antidepressive response revealed significant differences in both medication groups: Patients receiving escitalopram showed a 23% decrease of ADP induced aggregation (p = 0.03) and a 15% decrease of collagen induced aggregation (p = 0.03). With nortriptyline the increase in impedance was reduced by 29% after ADP induction (p = 0.046).Conclusion
Depressed patients have higher ex vivo platelet aggregation that may contribute to increased cardiovascular morbidity. After three months of antidepressant treatment with either escitalopram or nortriptyline, platelet aggregation was significantly reduced in antidepressant responders, irrespective of the antidepressant medication type. 相似文献4.
Saiz PA García-Portilla P Paredes B Corcoran P Arango C Morales B Sotomayor E Alvarez V Coto E Flórez G Bascaran MT Bousoño M Bobes J 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(6):1518-1524
Objective
To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior.Subjects and methods
227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.Results
There were no differences in genotype frequencies between the three groups. The −1438A/G [χ2 (df) = 9.80 (2), uncorrected p = 0.007] and IL-1α −889C/T [χ2 (df) = 8.76 (2), uncorrected p = 0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of −1438G/G or IL-1α −889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df) = 6.84 (2), p = 0.033] and between the polymorphisms APOE and IL-1RA (86 bp)n [LRT (df) = 12.21 (4), p = 0.016] in relation to suicide attempt lethality.Conclusion
These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior. 相似文献5.
Sublette ME Galfalvy HC Fuchs D Lapidus M Grunebaum MF Oquendo MA Mann JJ Postolache TT 《Brain, behavior, and immunity》2011,25(6):1272-1278
Background
Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with major depressive disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers.Methods
Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n = 31) and patients with MDD with (n = 14) and without (n = 16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels.Results
KYN levels differed across groups (F = 4.03, df = (2,58), and p = 0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t = 2.105, df = 58, and p = 0.040), who did not differ from healthy volunteers (t = 0.418, df = 58, and p = 0.677). In post hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters.Conclusion
These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior. 相似文献6.
Reiji Yoshimura Taro Kishi Hikaru Hori Atsuko Ikenouchi-Sugita Asuka Katsuki Wakako Umene-Nakano Nakao Iwata Jun Nakamura 《Progress in neuro-psychopharmacology & biological psychiatry》2012
Objective
Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.Subjects and methods
Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.Results
Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.Conclusion
Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order. 相似文献7.
Yoshimura R Kishi T Suzuki A Umene-Nakano W Ikenouchi-Sugita A Hori H Otani K Iwata N Nakamura J 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(4):1022-1025
Background
We investigated the relationship between a brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and the clinical response of patients with major depressive disorder to selective serotonin reuptake inhibitors (SSRIs; here, paroxetine and sertraline). In addition, serum BDNF levels in these patients were considered together with the clinical response.Methods
A total of 132 patients who met the DSM-IV criteria for major depressive disorder were enrolled in the study. 54 of these patients were male and 78 were female (age range, 20-74 years; mean ± S.D., 51 ± 15). The patients' clinical improvement was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17) before (T0) and at 8 weeks after the administration of SSRI treatment (T8). Patients with at least a 50% decrease in the HAMD-17 score were classified as responders.Results
No correlation was observed between the BDNF Val66Met polymorphism and response to SSRIs or between the BDNF Val66Met polymorphism and serum BDNF levels at T0. An inverse correlation was found between serum BDNF levels and HAMD-17 scores at T0.Conclusions
These results suggest that the BDNF Val66Met polymorphism is independent of both the response to SSRI treatment and serum BDNF levels. The findings in the present study reconfirm that the serum BDNF level is a state biomarker for depression. 相似文献8.
Wolkowitz OM Wolf J Shelly W Rosser R Burke HM Lerner GK Reus VI Nelson JC Epel ES Mellon SH 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(7):1623-1630
Objectives
The “neurotrophin hypothesis” of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response.Methods
Thirty un-medicated depressed subjects were treated with escitalopram (N = 16) or sertraline (N = 14) for 8 weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects.Results
Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p = 0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p < 0.001), and BDNF levels increased with treatment (p = 0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p < 0.01), and “Responders” to treatment (≥ 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did “Non-responders” (p < 0.05).Conclusions
These results confirm low serum BDNF levels in un-medicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants. 相似文献9.
William Berger Akhil Mehra Maryann Lenoci Thomas J. Metzler Christian Otte Gary Tarasovsky Synthia H. Mellon Owen M. Wolkowitz Charles R. Marmar Thomas C. Neylan 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Introduction
Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats.Objectives
This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response.Methods
Medically healthy male subjects (N = 16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5–20 mg/day) escitalopram monotherapy. BDNF levels were obtained at baseline, and at weeks 4, 8 and 12.Results
PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment. Despite a substantial improvement in PTSD symptoms, there was virtually no change in BDNF levels over time. Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r = 0.58, p = 0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial.Conclusions
PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects. 相似文献10.
Introduction
Formation of denser fibrin networks displaying impaired lysability has been reported in subjects at an increased risk of atherosclerosis. Given recent data on prothrombotic fibrin clot phenotype reported in patients with antiphospholipid syndrome (APS), we tested the hypothesis that altered fibrin clot properties are associated with increased intima-media thickness (IMT) observed in PAPS.Materials and methods
We studied 30 consecutive patients with PAPS and 30 controls matched for age, sex and the type of previous thromboembolism. We assessed plasma fibrin clot permeability (Ks) and clot lysis time (CLT) with their potential determinants. The IMT was measured in 3 segments of the carotid arteries.Results
Patients with APS had 15.2% lower Ks (p = 0.002) and 9.7% prolonged CLT (p = 0.039) compared with controls. The IMT in the APS group was greater in the common carotid artery (5.7%; p = 0.002), at the bifurcation (17.46%; p < 0.001), and the internal artery (9.26%; p = 0.015). Patients with triple positivity in the antiphospholipid antibody profile (n = 9; 30%) had lower Ks and greater IMT (both, p < 0.05), compared with those with single positivity (n = 13; 43.3%). Multivariate analysis adjusted for potential confounders showed that in APS patients, oxidized low-density lipoproteins (p = 0.019) were the only independent predictor of Ks, while thrombin activatable fibrinolysis inhibitor activity (p < 0.001) predicted CLT. Plasminogen activator inhibitor-1 (PAI-1) was found to be the independent predictor of the IMT in the common carotid artery (p = 0.004), and in the internal carotid artery (p < 0.001).Conclusions
Reduced Ks and susceptibility to lysis are associated with greater IMT in PAPS, which might contribute to the early atherosclerosis in this disease. 相似文献11.
Nakajima S Uchida H Suzuki T Watanabe K Hirano J Yagihashi T Takeuchi H Abe T Kashima H Mimura M 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(8):1983-1989
Rationale
Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.Objectives
We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.Method
Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.Results
Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).Conclusions
Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression. 相似文献12.
Background
Despite evolution of new antidepressant treatment, clinicians still encounter challenges in the treatment of depressed patients. Looking for new medications that can potentiate the effects of current antidepressants seems to be necessary. Our objective is to survey the efficacy of topiramate augmentation in resistant major depressive disorder (MDD).Method
This augmentation trial was designed as an 8-week randomized, placebo-controlled, double-blind study. Fifty three patients with DSM-IV diagnosis of MDD who had failed to respond to at least 8 weeks of treatment with an adequate dose of one of the SSRIs (fluoxetine, citalopram or serteraline) were included in the study. Patients were randomized to receive a flexible dose of topiramate (100-200 mg/day) or placebo beside their current antidepressant medication for a period of eight weeks. Outcome measures were Hamilton Depression Scale (HAM-D) and Clinical Global Impression (CGI).Results
42 patients completed the study and there were 6 and 5 dropouts in topiramate and placebo groups, respectively. The topiramate group demonstrated significant improvement over the study period based on mean HAM-D score at week 8 compared to baseline (P = .000, Z = 3.699). Those receiving topiramate demonstrated to have a mean decrease of 32.0% in HAM-D score, compared to only 5.5% for those receiving placebo. Depressed mood, suicidality, insomnia (early, middle and late), agitation and anxiety symptoms were significantly improved in the topiramate group.Conclusion
Our double-blind placebo-controlled study demonstrated that topiramate augmentation potentiate the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treatment of resistant major depressive disorder. Of note is that our study is preliminary and larger double-blind studies are needed to confirm the results. 相似文献13.
Aleksandra Matyja-Bednarczyk Jakub Swadźba Teresa Iwaniec Marek Sanak Sylwia Dziedzina Adam Ćmiel Jacek Musiał 《Thrombosis research》2014
Introduction
Antiphospholipid syndrome (APS) is associated with the risk of both arterial and venous thrombosis. However, it is not known which factors might determine the location of thrombosis.Materials and Methods
To retrospectively characterize factors associated with the risk of arterial thrombosis in a cohort of APS patients. Analysis included laboratory and clinical criteria of APS, together with classical cardiovascular risk factors and the possible role of platelet integrin α2β1 (807 C/T) and αIIbβ3 (PI A1/2) genetic polymorphisms. We enrolled 163 APS patients (123 women and 40 men aged 21-75; mean age 43 years); 78 suffered from arterial thrombosis.Results
There were no significant differences in the frequency or titers of different antiphospholipid antibodies with the exception of slightly increased frequency of IgG anticardiolipin antibodies (ACL) in the arterial thrombosis group. Livedo reticularis was observed significantly more often in the arterial thrombosis group, particularly in stroke patients.In univariate analysis arterial thrombosis was associated with male gender (OR-2,201; p = 0,033), arterial hypertension (OR-2,81; p = 0,002) and hypercholesterolemia (OR-3,69; p = 0,001). On multivariate analysis arterial hypertension (OR = 1,78; p = 0,008) and hypercholesterolemia (OR = 2,001; p = 0,002) remained as independent risk factors for arterial thrombosis. Platelet glycoprotein polymorphisms studied did not show any significant associations with arterial thrombosis in APS patients.Conclusions
Among APS patients those with ACL IgG antibodies, having livedo reticularis, and suffering from hypertension an hypercholesterolemia are at the increased risk of arterial thrombosis. 相似文献14.
Kristen M. Kochanski-Ruscio Jaime T. Carreno-PonceKathryn DeYoung Geoffrey GrammerMarjan Ghahramanlou-Holloway 《Comprehensive psychiatry》2014
Introduction
Individuals with multiple versus single suicide attempts present a more severe clinical picture and may be at greater risk for suicide. Yet group differences within military samples have been vastly understudied.Purpose
The objective is to determine demographic, diagnostic, and psychosocial differences, based on suicide attempt status, among military inpatients admitted for suicide-related events.Method
A retrospective chart review design was used with a total of 423 randomly selected medical records of psychiatric admissions to a military hospital from 2001 to 2006.Results
Chi-square analyses indicated that individuals with multiple versus single suicide attempts were significantly more likely to have documented childhood sexual abuse (p =.025); problem substance use (p = .001); mood disorder diagnosis (p = .005); substance disorder diagnosis (p =.050); personality disorder not otherwise specified diagnosis (p =.018); and Axis II traits or diagnosis (p = .038) when compared to those with a single attempt history. Logistic regression analyses showed that males with multiple suicide attempts were more likely to have problem substance use (p = .005) and a mood disorder diagnosis (p =.002), while females with a multiple attempt history were more likely to have a history of childhood sexual (p =.027).Discussion
Clinically meaningful differences among military inpatients with single versus multiple suicide attempts exist. Targeted Department of Defense suicide prevention and intervention efforts that address the unique needs of these two specific at-risk subgroups are additionally needed. 相似文献15.
Reiji Yoshimura Atsuko Ikenouchi-SugitaHikaru Hori Wakako Umene-NakanoAsuka Katsuki Kenji HayashiNobuhisa Ueda Jun Nakamura 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Only two-thirds of depressive patients respond to antidepressant treatment. Recently, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we examined the effects of various atypical antipsychotic drugs as adjuvant to antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants and mood stabilizers, on plasma BDNF levels in refractory depressed patients. Forty-five patients who met the DSM-IV criteria for major depressive disorder (n = 31) or bipolar disorder (10 with bipolar I, 4 with bipolar II) were enrolled in the study. Twenty-one were male and 24 were female, and their ages ranged from 28 to 71 (mean ± SD = 49 ± 12) years. Plasma BDNF levels were measured using a sandwich ELISA. The plasma BDNF levels in responders (those showing a decline in HAM-D scores of 50% or more) were significantly increased 4 weeks after the administration of each atypical antipsychotic drug, while the levels in non-responders were not changed. Furthermore, there was a significant correlation between the changes in HAM-D scores and the changes in plasma BDNF levels. These results suggest that adding an atypical antipsychotic drug to ongoing treatment with an antidepressant or mood stabilizer is useful and well-tolerated for refractory depressed patients, and the efficacy of atypical antipsychotics as an adjuvant might involve an increase of plasma BDNF levels. 相似文献
16.
Johanna Hilli Tuomas Korhonen Kari Laine 《Progress in neuro-psychopharmacology & biological psychiatry》2009
Objectives
To evaluate the potential of pharmacodynamic and pharmacokinetic interactions of a concomitantly administered monoamine oxidase (MAO) type B inhibitor rasagiline and a selective serotonin reuptake inhibitor (SSRI) escitalopram.Methods
Twelve healthy male volunteers received a 10-day regimen of rasagiline 1 mg daily, followed by concomitant rasagiline 1 mg and escitalopram 10 mg daily for 7 days.Results
We found that the drug combination was generally well tolerated, and there were no signs of central nervous system hyperexcitation or changes in the subjects' vital signs. The reported adverse effects were mainly mild or moderate, and typical for SSRIs. The MAO-A-dependent catecholamine metabolite DHPG levels did not change significantly during the study suggesting that rasagiline's MAO-B selectivity was preserved. The plasma monoamine concentrations indicated no subclinical signs of interaction. As expected, the whole blood serotonin was significantly reduced by escitalopram but unaffected by rasagiline. Rasagiline AUC was increased by 42% (p < 0.0001) and the weight-adjusted apparent oral clearance was reduced by 35% (p = 0.0009) after 7 days' concomitant escitalopram treatment. Escitalopram reduced the ratio of the AUC values of the main metabolite 1-aminoindan and rasagiline by about 23% (p = 0.0079). There were no significant changes in the elimination half-life, tmax and Cmax of rasagiline.Conclusions
These results suggest good tolerability of concomitant administration of rasagiline and escitalopram. However, other medications, diseases and aging may change the individual drug response and tolerability of concomitant rasagiline and escitalopram, e.g. in Parkinsonian patients, and thus careful monitoring is recommended when combining rasagiline and escitalopram. 相似文献17.
Leonardo Lorente María M. Martín Juan M. Borreguero-León Jordi Solé-Violán José Ferreres Lorenzo Labarta César Díaz Alejandro Jiménez José A. Páramo 《Thrombosis research》2014
Background
Higher plasma plasminogen activator inhibitor-1 (PAI-1) levels have been reported in septic patients. However, some questions remain unanswered, such as whether there is an association between plasma PAI-1 levels and sepsis severity and mortality, and inflammation state during the first week.Methods
Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units of 260 patients with severe sepsis. Circulating levels of PAI-1 and tumour necrosis factor (TNF)-α were measured at day 1, 4 and 8. End-point was 30-day mortality.Results
Nonsurviving septic patients (n = 89) presented higher PAI-1 levels than surviving (n = 171) at day 1 (58.4 (33.3-83.8) vs 36.5 (21.1-62.5) ng/mL; p < 0.001), 4 (34.0 (14.7-53.3) vs 16.2 (10.2-27.4) ng/mL; p < 0.001) and 8 (30.6 (16.2-47.8) vs 18.9 (10.4-29.5) ng/mL; p = 0.004). We found a positive correlation of PAI-1 levels with SOFA, lactic acid, aPTT, INR and TNF-α, and negative with platelet count at day 1, 4 and 8. Logistic regression analyses showed that PAI-1 levels at day 1 (p < 0.001), 4 (p < 0.001) and 8 (p = 0.001) were associated with 30-day mortality. On ROC curve analysis to predict 30- day survival, the area under the curve of PAI-1 levels at day 1, 4 and 8 were 0.65 (95% CI = 0.58-0.72; p < 0.001), 0.69 (95% CI = 0.60-0.78; p < 0.001) and 0.65 (95% CI = 0.54-0.75; p = 0.005) respectively.Conclusions
The most interesting findings of our study, to our knowledge the largest series reporting PAI-1 levels during follow-up in septic patients, were that plasma PAI-1 levels during the first week were associated with inflammation, severity and mortality. 相似文献18.
Background
Point of care (POC) devices measuring the international normalized ratio (INR) are accurate for patients with stable disease, but their efficiency has not been prospectively assessed during the “bridging period” when patients are receiving a low molecular weight heparin (LMWH) on top of a vitamin K antagonist (VKA) until the target INR is reached.Methods
188 dual INR measurement using the POC (INRPOC) and the laboratory (INRlab) at the same time were consecutively determined : 69 in patients receiving LMWH + VKA (bridging group) and 119 in patients receiving only a VKA (control group). INRpoc was compared to INRlab.Results
Test strip failure rate was higher in the bridging group than in the control group (29% vs 4% ; p < 0,001).In successful tests, POC accuracy was not modified by LMWH administration: the correlation coefficients between POC and lab INR values for the bridging group and the control group were 0,81 and 0,87 respectively, and the relative measure of divergence (RMD = INRlab - INRpoc / INRlab) was lower in the bridging group than in the control group (4 ± 7% vs 10 ± 14%; p = 0,02). Finally, clinically relevant agreement between POC and laboratory was of 90% in the bridging group and 92.1% in the control group (p = 0.6).Conclusion
With the POC used (INRatio), in patients receiving LMWH when the POC gives a result, it is as accurate as in patients not receiving a LMWH. 相似文献19.
Background
Retrieval rates of optional recovery inferior vena cava (IVC) filters in US hospitals range from 11 - 70%. We conducted a retrospective study in a Canadian tertiary care centre to determine retrieval rates and predictors of filter removal.Methods
Consecutive patients who had a retrievable IVC filter inserted or removed between January 2007 and December 2010 were identified. Data collected included baseline demographics, indications for filter insertion and removal, documentation of an IVC filter management plan, reasons for non-retrieval, complications, and death.Results
275 patients with a median age of 60 years were followed in hospital for a median of 17 patient-days (range 1–876). Indications for filter placement were acute or prior VTE with contraindication to anticoagulation (72.4%), high risk of PE (11.3%) and primary prophylaxis (13.8%). Retrieval was attempted in 165 patients (60%) and was successful in 146 patients (53.1%). The most common reason for failed retrieval was filter thrombus. Predictors of attempted retrieval included documentation of filter plan (odds ratio [OR] 16.7; p < 0.001), surgical indication for IVC filter insertion (OR 4.8; p = 0.002), age ≤ 70 years (OR 3.8; p = 0.001), Hematology service involvement (OR 3.0; p = 0.006), and presence of metastatic cancer (OR 0.2; p = 0.001). Thrombotic complications occurred in 48 patients, including 3 patients who died of fatal PE.Conclusion
Our filter retrieval rate is suboptimal. Improvements in follow-up documentation or a dedicated clinical service may help increase retrieval rates. 相似文献20.
Mehmet Sevki Uyanik Gulsum Emel Pamuk Omer Nuri Pamuk Sedat Alpaslan Tuncel 《Thrombosis research》2014