Escitalopram versus paroxetine for social anxiety disorder: an analysis of efficacy for different symptom dimensions.

BACKGROUND: A previous factor analysis of pooled data demonstrated that the Liebowitz Social Anxiety Scale (LSAS) can be divided into six subscales. This paper examines data from a fixed-dose trial of escitalopram versus paroxetine, in order to determine the differential effects of these agents on symptom dimensions in social anxiety disorder (SAD). METHODS: Data from a 24-week randomised, placebo-controlled, comparative study of fixed doses of escitalopram (5 mg, 10 mg, 20 mg) versus paroxetine (20 mg) in SAD were examined. The six factors identified in a previous factor analysis of baseline data from escitalopram studies on the primary efficacy scale, the LSAS, were used to compute subscale scores. These were analysed using analysis of covariance (ANCOVA), and standardised effect sizes were calculated. RESULTS: The combined escitalopram data and the paroxetine data both demonstrated significant superiority to placebo on each of the 6 LSAS factors at week 24 (OC analysis). Escitalopram doses of 5 mg, 10 mg, and 20 mg were generally more effective than placebo for each of the factors. Escitalopram 20 mg was significantly more effective than paroxetine 20 mg on 5 of the 6 symptom dimensions. CONCLUSION: Factor analysis of the LSAS allows for useful secondary analyses that support and extend the primary efficacy analysis of this instrument. The analysis here indicates that different escitalopram doses are effective across the various symptom dimensions of SAD.     

度洛西汀与帕罗西汀治疗伴有疼痛症状的抑郁障碍患者的对照研究简

目的：比较度洛西汀与帕罗西汀治疗伴有疼痛症状的抑郁障碍患者的疗效和安全性。方法：对本院60例符合CCMD-3抑郁症的诊断标准并伴有疼痛症状的抑郁障碍患者随机分为研究组（30例）和对照组（30例）,研究组给予度洛西汀肠溶胶囊,起始剂量40mg／d,最高为60mg／d,对照组给予帕罗西汀,起始剂量20mg／d,最高为40mg／d。分别治疗8周。用汉密尔顿抑郁量表（HAMD-17）项和临床大体印象量表（CGI-SI）评定疗效,用副反应量表（TESS）评定药物安全性,采用国外经典的疼痛视觉模拟评分（VAS）评估疼痛严重程度。结果：治疗后两组疗效相比无显著性差异,但在第1周末研究组HAMD评分显著低于对照组,且差异具有显著性（P〈0．05）,对疼痛症状改善,研究组比对照组明显。结论：度洛西汀可快速、有效地改善抑郁症状,且能明显改善抑郁患者的躯体疼痛症状。     

Hepatitis C virus infection: immune responsiveness and interferon-alpha treatment

Hepatitis C virus (HCV) is responsible for most cases of posttransfusion hepatitis and sporadic or community-acquired non-A, non-B hepatitis. Different generations of enzyme-linked immunosorbent assay have been generated for detecting antibodies to HCV epitopes. HCV-RNA quantitative analysis has been developed by means of polymerase chain reaction technique. This approach is the only reliable method for HCV-RNA tissue localization, being helpful in early diagnosis. HCV infected liver is characterized by an inflammatory infiltrate including CD4+, CD8+, and B lymphocytes. Evidence has been provided that in HCV patients CD8+ cell response is associated with low level of viraemia and higher level of disease activity. CD4+ T cells exhibit specificity for the core antigen, also correlating with disease activity and viraemia. Costimulatory molecules, cytokines, oxygen radicals, the complex Fas/Fas-ligand and soluble class I HLA structures are discussed as putative cofactors involved in disease evolution. Various forms of interferon (IFN)-alpha have been evaluated for the treatment of patients with HCV infection. Initial enthusiasm has been attenuated by the evidence of a low sustained virological response rate and the constant side effects of IFN-alpha therapy in patients with chronic HCV disease. Among possible markers for predicting therapeutic outcome in HCV-positive individuals, anti-core antibodies correlate positively with response to IFN-alpha administration, as well as reduction of interleukin-2 serum levels has been detected in patients with a good therapeutic response. Association between HCV infection and autoimmune phenomena, also in relation to IFN-alpha therapy has been reported. Finally, results of the combined treatment with IFN-alpha/ribavirin are illustrated.     

Neurobehavioral teratogenic effects of thalidomide in rats.

Thalidomide-induced embryopathy has been known for four decades, however, the drug has been reintroduced for human use in a number of countries, including the United States. In utero thalidomide exposure in humans is associated with central nervous system (CNS) effects in addition to the well-known limb, ear and other malformations. Despite knowledge of these CNS effects, not a single experimental study could be found that examined thalidomide for possible developmental neurobehavioral effects. In the present experiment, gravid Sprague-Dawley rats were treated with either thalidomide (100 mg/kg by gavage) or vehicle (propylene glycol) on embryonic days E7-18 and allowed to deliver and raise their own offspring. The offspring were evaluated in a series of neurobehavioral tests (reflexes, locomotor activity, startle reactivity and learning in the Morris and Cincinnati water mazes). There was a small reduction in maternal weight among thalidomide-treated dams during midgestation. Thalidomide offspring showed increased preweaning mortality and male-specific, late onset reduction in growth that persisted until the end of the study. Male thalidomide offspring showed significant increases in errors and latency in the multiple-T Cincinnati water maze. Although rats are refractory to thalidomide-induced teratogenesis, the present results suggest that thalidomide selectively impairs offspring survival and growth and at least one type of learning among male offspring.     

Effects of interferon-alpha monotherapy on hepatic drug metabolism in cancer patients.

1. The influence of interferon-alpha (IFN alpha) on the clearances of theophylline (TH), antipyrine (AP) and hexobarbitone (HB) was studied in seven cancer patients given IFN alpha as their only treatment. In addition, IFN alpha effects on drug clearance were correlated with changes in serum inflammatory cytokines and acute phase proteins. 2. A 'baseline' study was performed by administering an oral drug 'cocktail' of TH (150 mg), AP (250 mg) and HB (250 mg) with saline injected simultaneously and again 24 h later. One week later, an 'acute' study was performed at the initiation of IFN alpha therapy, 3 x 10(6) units injected with the drug cocktail and again 24 h later. After 2 weeks of IFN alpha treatment three times per week, a 'chronic' study was performed with IFN alpha injected the day prior to, simultaneously with, as well as 24 h after the drug cocktail. 3. Plasma samples were collected over 48 h and the clearances of TH, AP and HB were estimated. Serum samples were collected at various times for the measurement of tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (C-RP) and alpha 1-acid glycoprotein (AGP). 4. IFN alpha caused a 33% decrease in the oral clearance of TH during the chronic study compared with baseline (P < or = 0.05). Although IFN alpha inhibited TH clearance by 16% during the acute study and AP clearance by 20-21% during both acute and chronic studies, these changes did not reach statistical significance. IFN alpha caused minimal changes in HB clearance. There were no chronic effects of IFN alpha on serum cytokines or acute phase proteins. 5. The findings confirm that the most commonly used dose of IFN alpha inhibits the hepatic clearance in humans of some but not all drugs and that this inhibition persists during IFN alpha therapy. Because inhibition was not associated with increases in serum cytokines or acute phase proteins, the mechanism by which IFN alpha inhibits cytochrome P450 activities in vivo does not appear to involve inflammatory mediators such as TNF. IL-1 or IL-6.     

Neurobehavioral effects of prenatal alcohol: Part I. Research strategy

This paper, Part I of a three-part series, reviews the literature on the neurobehavioral effects of prenatal alcohol exposure and describes a large group of tests assembled to assess neurobehavioral outcomes of alcohol teratogenesis in 7-year-old children. This paper presents the distribution of these test scores for our sample and discusses their relationships with an alcohol binge score and with full-scale IQ. This group of tests is suitable for children with a wide range of abilities and provides a broad assessment of neurobehavioral deficits. Part II of this series describes a new method of statistical analysis, Partial Least Squares (PLS), which is particularly well suited to complex multivariate data sets such as these, and with its aid, examines the effects of prenatal alcohol exposure on IQ, achievement, vigilance and classroom behavior, a total of 43 outcome scores. Part III examines prenatal alcohol effects on outcomes from the broad group of 164 scores deriving from 17 neuropsychologic tests, using the Partial Least Squares methodology, and summarizes the implications of our findings for the behavioral teratology of alcohol.     

Changes in the Temperament and Character Inventory dimensions after paroxetine treatment in patients with major depressive disorder

Previous studies have reported changes in the dimensions of the Temperament and Character Inventory (TCI) after patients with major depressive disorder are treated. We aimed to investigate the changes in the TCI dimensions after paroxetine treatment in patients with major depressive disorder. Forty‐eight patients were enrolled in this study and were treated with 10–40 mg/day of paroxetine for 6 weeks. The TCI was completed twice, at weeks 0 and 6. We used the Montgomery–Asberg Depression Rating Scale (MADRS) to evaluate patients. The participants were divided into three groups (responders, non‐responders, and early responders) based on treatment response. The scores of each dimension of the TCI were compared before and after treatment using repeated‐measures two‐way analyses of variance. In the responders group (n = 24), no TCI dimension scores changed significantly during treatment, but the interaction between sex and MADRS score change was significantly associated with the results. In the non‐responders group (n = 15), the self‐directedness score increased significantly during the treatment period (p = 0.000), and the change in MADRS score significantly affected the results. In the early responders group (n = 9), no TCI dimension scores changed significantly during treatment. The results of the present study may reveal a possible correlation between paroxetine treatment and changes in personality traits. Copyright © 2015 John Wiley & Sons, Ltd.     

Reboxetine versus paroxetine versus placebo: effects on cognitive functioning in depressed patients

Impaired cognitive functioning is often associated with major depressive disorder (MDD). Moreover, a number of agents used to treat MDD are known to have negative effects on cognitive functioning. We report an assessment of the effects of the selective norepinephrine reuptake inhibitor reboxetine, the selective serotonin reuptake inhibitor paroxetine, and placebo on a variety of measures of cognitive functioning in patients with MDD. Cognitive functioning in 74 adult patients (aged 18-65 years) with a confirmed diagnosis of MDD (DSM-IV) was assessed as part of two identical, randomized, double-blind, placebo- and active-treatment-controlled, fixed/flexible dose comparisons of 8 weeks of treatment with reboxetine (8-10 mg/day), paroxetine (20-40 mg/day) and placebo. Cognitive function was assessed at baseline, day 14 and day 56 using a selection of tasks from the Cognitive Drug Research computerized assessment system, including Simple Reaction Time, Digit Vigilance, Choice Reaction Time, Numeric Working Memory, Word Recognition and Critical Flicker Frequency. The results in the 74 patients (reboxetine n = 25, paroxetine n = 23, placebo n = 26) showed that reboxetine significantly improved the ability to sustain attention at day 56 compared with baseline (P = 0.023). In addition, patients who received reboxetine experienced significant improvements in their speed of cognitive functioning when tested at day 56 compared to baseline (P = 0.024). No significant changes or trends in this direction were seen among patients who received either placebo or paroxetine. The results of the present study provide objective data to support the possibility that reboxetine favourably affects cognitive processes in depressed patients.     

Genetic associations between the ADHD symptom dimensions and Cloninger's temperament dimensions in adult twins

Previous studies have identified phenotypic associations between Cloninger's temperament dimensions and the symptoms of attention deficit hyperactivity disorder (ADHD) in adults. However the underlying aetiology of these associations remains unclear. We investigate the extent to which genetic and environmental influences contribute to the relationship between temperament and ADHD, examining the ADHD symptoms of inattention (IA) and hyperactivity/impulsivity (HI) separately. Participants were 886 adult twin pairs aged 19–20 years. ADHD symptoms of IA and HI were measured using a DSM-IV based rating scale. Temperament was measured using Cloninger's Temperament and Character Inventory (TCI), across four dimensions: novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PS). The twin method was used to decompose phenotypic variance/covariance among these variables into genetic and environmental components. We found that NS was genetically associated with both ADHD symptom dimensions (IA and HI), but that HA was genetically associated with IA only. There was also some evidence of genetic association between PS, IA and HI. These findings suggest that unique profiles of temperament are genetically related to the two ADHD symptom dimensions in adults. Further work is now needed to elucidate the mechanisms that underlie both the combined and separate symptom factor domains of ADHD.     

Neurobehavioral effects of perinatal AZT exposure in Sprague-Dawley weaning rats.

Because AZT (azidothymidine, zidovudine, ZDV) has become the standard of care for preventing HIV transmission during pregnancy, we conducted a study to assess the possible neurobehavioral effects of this drug, using a rat model. Each litter was randomly assigned to a treatment group: vehicle, AZT 50, 100, or 150 mg/kg, or no treatment. Treatments were administered once daily via gastric intubation, prenatally from gestation day (G) 19-22 and then postnatally from postnatal day (PND) 2-20, except the nontreated group, which was only weighed every 4 days. On PND21 each rat was given a single dose of amphetamine (0.25, 0.50, 0.75, or 1.0 mg/kg) or saline and placed in the Accuscan activity chamber for 1 h of data collection and video taping. Results show that all of the behaviors analyzed produced statistically significant main effects of perinatal treatment, challenge drug, and time block. For distance traveled, there was a significant three-way interaction between treatment, sex, and time block, an effect that was independent of the effects of handling and injecting the rats. That is, within the males, the AZT 150 group displayed the greatest amount of locomotion, while among the females, the AZT 50 group was the most active. Furthermore, the AZT 50 group showed significantly less margin time (wall hugging) and more grooming than the nontreated control group. However, handling contributed to these differences because they were not observed when the vehicle-intubated group was used as the control. Across all treatment groups, amphetamine increased locomotion, the duration of rearing, and sniffing, while it decreased wall hugging, grooming, and time spent quiet. Complex interactions between amphetamine dose and time block were also seen for each behavior. In summary, these data indicate that amphetamine, at the doses used in the current study, alters behavior in the rat at 21 days of age, and that perinatal AZT exposure alters behavior in a single domain, locomotion with the threshold for this effect depending on genders.     

Neurobehavioral effects of perinatal AZT exposure in Sprague-Dawley adult rats.

Since AZT (azidothymidine, zidovudine, ZDV) has become the standard of care for preventing human immunodeficiency virus transmission during pregnancy, we conducted a study to assess the possible long-term neurobehavioral effects of AZT, using a rat model. Each litter was randomly assigned to a treatment group: no treatment, vehicle or AZT 50, 100, or 150 mg/kg. Treatments were administered once daily via gastric intubation, prenatally from gestation day (G) 19-22 and then from postnatal day (PND) 2-20. Between PND 59-65, each rat was given a single dose of amphetamine (0.1, 0.5, 1.0, or 2.0 mg/kg) or saline and placed in the Accuscan activity chamber for 1 h of data collection and video taping. There was a significant interaction between perinatal treatment and amphetamine challenge drug for one behavioral category, distance traveled, which was due to differences in the nontreated control group compared to all treated groups. These data indicate that chronic AZT treatment at three dose levels during the perinatal period produces no lasting changes in response to amphetamine in the open field in the rat.     

Neuropsychiatric adverse effects of interferon-alpha: recognition and management

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.     

Neurobehavioral effects of dietary restriction in rats

The effects of reduced body weight gain on nervous system function of young male Fischer 344 rats were examined. The rats were fed 15% ('mild') or 50% ('severe') less than the controls. Mild and severe dietary restriction resulted in 9% and 38% lower body weight compared to the controls. Mild dietary restriction caused slight changes in flash evoked potentials, auditory brainstem responses, caudal nerve action potentials, and body temperature. Severe dietary restriction increased the magnitude of the effects noted in the mild group, as well as causing a significant decrease in grip strength. Somatosensory evoked responses were not affected by either mild or severe restriction. Diet restricted rats were more excitable while restrained for testing. Thus, dietary restriction has significant effects on numerous behavioral and neurophysiological parameters that should be considered in the interpretation of neurotoxicological data when body weight differences are present.     

Neurobehavioral teratogenic effects of clomipramine and alpha-methyldopa

Neonatal treatment of rats with centrally acting drugs such as clomipramine was shown to affect adult body and brain weight, behavior and sleep. We made a further study of the effects of clomipramine and tested one dose of alpha-methyldopa. Male rats were treated twice daily with saline, 7.5 or 15 mg/kg clomipramine or 100 mg/kg alpha-methyldopa from postnatal day 2-14 and tested in adulthood for effects on acquisition of radial maze behavior, on problem solving behavior in Hebb-Williams mazes, sexual performance and sleep-wake patterns. Clomipramine-treated rats had reduced body weight. No effects of neonatal drug treatment were found on several measures in the two mazes. Ejaculating rats in all three treatment groups showed longer latencies for sexual behavior and clomipramine-treated rats showed fewer ejaculations. Clomipramine-treated rats spent more time sleeping than the controls during the 24 hr sleep-wake recordings in adulthood.     

The effects of anticancer chemotherapeutic drugs on cognitive function and other neuropsychiatric dimensions in breast cancer patients

This preliminary study aimed to apply a novel computerized measure derived from the content analysis of 5-min speech samples from patients with breast cancer to measure cognitive impairment and other neuropsychiatric dimensions during the course of anticancer chemotherapeutic treatment. Since such patients are often administered other pharmacological agents to alleviate their symptoms in addition to anticancer chemotherapeutic agents, another aim was to try to distinguish the mental effects of the anticancer drugs from the effects of any other drugs administered. Before and during the course of their anticancer chemotherapy, 12 breast cancer patients gave 5-min verbal samples, elicited by purposely ambiguous instructions, to talk about any personal life experiences. The recorded verbal samples were scored by a computer program (PCAD 2000) to measure the magnitude of cognitive impairment and other relevant neuropsychiatric dimensions. All of the pharmacological agents administered to the patients were recorded. The computer program automatically compared the scores derived from each verbal sample to already established norms to determine whether each score was within normal limits or one to three standard deviations from the norms. Significantly elevated Cognitive Impairment Scale scores were found in the verbal samples of 9 of the 12 patients. All patients had instances of elevated Health/Sickness Content Analysis Scale scores as well as frequent significantly elevated scores in shame anxiety and in death anxiety. In the Quality of Life Content Scale, the scores were uniformly low, ranging from +1.64 to -9.11. Further studies are being carried out to determine which patients are especially susceptible to cognitive impairment under these treatment conditions.     

Neurobehavioral effects of prenatal alcohol: Part II. Partial least squares analysis

This paper, the second in a series of three, introduces Partial Least Squares (PLS) methods for assessing the effects of moderate levels of prenatal alcohol exposure on performance and behavior in young school-age children. Studies of human behavioral teratology pose statistical problems for which standard multiple regression methods are inadequate. Prenatal alcohol exposure, the teratogenic "dose," can be assessed only indirectly through a variety of measures of alcohol consumption. Similarly, the behavioral outcomes we examine--IQ, achievement, classroom behavior, and vigilance--are each measured indirectly in terms of multiple items or indicators. We find that a single latent variable, estimated as a linear combination of the measures of alcohol consumption, provides an appropriate measure of "dose" for summarizing the relationships between alcohol exposure and each of the four blocks of outcome variables. A pattern of alcohol consumption emphasizing binge behavior (i.e., reporting average consumption of multiple drinks per drinking occasion, or at least five drinks on any single occasion) in the period prior to recognition of pregnancy is significantly correlated with latent variables computed from each of the four outcome blocks: IQ, academic achievement, classroom behavior and attention/vigilance.     

Neurobehavioral effects of prenatal alcohol exposure at 26 months.

Effects of prenatal alcohol exposure on the Bayley Scales of Infant Development were evaluated at 13 and 26 months and on three language measures at 26 months, in 92 economically disadvantaged, African American toddlers. After consideration of 17 potential confounders, a significant alcohol-related deficit in the Mental Development Index (MDI) was seen at 13 months as was a tendency for poorer Psychomotor Development Index (PDI) performance. The PDI deficit continued to be evident at 26 months. When the 26-month MDI was factor analyzed, four factors emerged: Linguistic Representation, Spatial Fine Motor, Other Fine Motor, and Relational Representation. As in a previous study of these children at 13 months of age, Spatial Fine Motor deficits were specifically associated with prenatal alcohol exposure. These findings appear consistent with reports relating prenatal alcohol exposure to poorer spatial visualization and spatial memory in adolescence. No effects of prenatal exposure were detected on language. Maternal postpartum drinking was associated with decreased language intelligibility.     

Marihuana use by pregnant women: Neurobehavioral effects in neonates

In a prospective study of 291 mothers-to-be, 20 per cent reported some use of marihuana before and/or during prenancy. A significant increase in symptoms associated with nervous system abnormalities was observed among babies born to heavy regular marihuana users and visual responses were affected in two- to three-day-old infants in a dose-related fashion. No relationship between marihuana use and maternal weight gain, length of gestation, duration of labor or birthweight was found.     

芳香疗法在癌症患者症状管理中的应用进展

随着全球癌症发病率的日益攀升,癌症已成为威胁人类生命与健康的"头号杀手".芳香疗法作为一种补充照护手段,具有减轻疼痛、改善睡眠、缓解焦虑抑郁、防止皮肤干燥等作用,在欧美国家已被广泛应用于安宁疗护领域,近年来国内也已开始相关的临床研究和应用.本文阐述芳香疗法的概念、种类、使用方法和作用机制,综述芳香疗法在癌症患者恶心呕吐...