D-Cycloserine Augmentation of Exposure Therapy for Post-Traumatic Stress Disorder: A Pilot Randomized Clinical Trial

Viewing post-traumatic stress disorder (PTSD) as a disorder of emotional learning, this study used a cognitive enhancer synergistically with virtual reality exposure (VRE) therapy for the treatment of PTSD. The main objective was to determine if a novel pharmacotherapy, D-cycloserine (DCS), enhanced the efficacy of the psychotherapy. Pre-clinical studies suggest that when fear extinction occurs during DCS administration, neuroplasticity may be enhanced. VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients. In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2. Assessments occurred at pre-treatment, following sessions 3, 6, 10, post-treatment, and at 6 months. The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively). A similar pattern was observed for depression, anger expression, and sleep. PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months). Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group. These results suggest a promising new treatment for PTSD.     

White Matter Integrity in Highly Traumatized Adults With and Without Post-Traumatic Stress Disorder

Prior structural imaging studies of post-traumatic stress disorder (PTSD) have observed smaller volumes of the hippocampus and cingulate cortex, yet little is known about the integrity of white matter connections between these structures in PTSD samples. The few published studies using diffusion tensor imaging (DTI) to measure white matter integrity in PTSD have described individuals with focal trauma rather than chronically stressed individuals, which limits generalization of findings to this population; in addition, these studies have lacked traumatized comparison groups without PTSD. The present DTI study examined microstructural integrity of white matter tracts in a sample of highly traumatized African-American women with (n=25) and without (n=26) PTSD using a tract-based spatial statistical approach, with threshold-free cluster enhancement. Our findings indicated that, relative to comparably traumatized controls, decreased integrity (measured by fractional anisotropy) of the posterior cingulum was observed in participants with PTSD (p<0.05). These findings indicate that reduced microarchitectural integrity of the cingulum, a white matter fiber that connects the entorhinal and cingulate cortices, appears to be associated with PTSD symptomatology. The role of this pathway in problems that characterize PTSD, such as inadequate extinction of learned fear, as well as attention and explicit memory functions, are discussed.     

Re-traumatization Cycle: Sexual Abuse,Post-Traumatic Stress Disorder and Sexual Risk Behaviors among Club Drug Users

Background: Club drug users are high risk and vulnerable population for adverse drug-related consequences and sexual risk behaviors. Few investigations have addressed the possible interrelationship between early trauma and PTSD among young club drug using populations. Objective: Exposure to traumatic experiences – especially in childhood, has been linked to risk behaviors exposure and substance use disorder. This study aimed to assess and compare drug use patterns and the presence of childhood sexual abuse (CSA) experiences among ecstasy and LSD users with and without Posttraumatic Stress Disorder (PTSD). Method: This cross-sectional study employed targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals. The Global Appraisal of Individual Needs questionnaire was used as the primary assessment instrument. Participants were from 18 to 39?years of age, had used ecstasy and/or LSD in the 90?days prior to the interview, and were not in treatment for alcohol and other drug problems. Results: Out of the 240 participants, 123 (51.2%) presented PTSD symptoms. Those presenting PTSD were younger, less educated, with lower income, and presented higher drug use severity than those without PTSD symptoms. Moreover, a higher prevalence of sexual risk behavior was verified among those with PTSD. There was an association between PTSD symptoms and CSA history, where 64.2% of individuals with PTSD also presented CSA, compared to 47% among those without PTSD (p?=?.028). Individuals with co-occurring history of CSA and PTSD symptoms reported earlier use of ecstasy, LSD, and cocaine compared to individuals with a history of CSA but without PTSD. Conclusions: In the present study, participants with a history of PTSD demonstrate a history of CSA, as well as pronounced severity in several areas – precocity of use, severity of addiction, and greater exposure to situations of sexual risk. Thus, a cycle of traumatization may be established through early potential trauma, which can remain unprocessed and contribute to earlier and more severe substance use and sexual risk behaviors. Identification of PTSD symptoms and risk for HIV and other STIs among young club drug users is critical to address focused treatment approaches for this vulnerable population.     

Interaction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress Disorder

FKBP5 regulates the cortisol-binding affinity and nuclear translocation of the glucocorticoid receptor. Polymorphisms at the FKBP5 locus have been associated with increased recurrence risk of depressive episodes and rapid response to antidepressant treatment. A recent study showed that FKBP5 genotypes moderated the risk of post-traumatic stress disorder (PTSD) symptoms associated with childhood maltreatment. One thousand one hundred forty-three European Americans (EAs) and 1284 African Americans (AAs) recruited for studies of the genetics of substance dependence were also screened for lifetime PTSD. Four single-nucleotide polymorphisms (SNPs) in FKBP5, rs3800373, rs9296158, rs1360780, and rs9470080, were genotyped on the complete sample. Logistic regression analyses were performed to explore the interactive effect of FKBP5 polymorphisms and childhood adversity on the risk for PTSD. After correction for multiple testing, childhood adversity significantly increased the risk for PTSD. FKBP5 genotypes were not associated with the development of the disorder. In AAs, one of the SNPs, rs9470080, moderated the risk of PTSD that was associated with childhood abuse. Without childhood adverse experiences, participants with the TT genotype of this SNP had the lowest risk for PTSD, whereas they had the highest risk for PTSD after childhood adversity exposure. In addition, in EAs, alcohol dependence was observed to interact with childhood adverse experiences, and also FKBP5 polymorphisms, to increase the risk for PTSD. This study provides further evidence of a gene × environment effect of FKBP5 and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations.     

艾司西酞普兰联合喹硫平治疗广泛性焦虑障碍的疗效观察

目的 评价艾司西酞普兰联合喹硫平治疗广泛性焦虑障碍(GAD)的疗效、安全性和可行性。方法 采用随机、双盲、平行对照研究。60例患者随机分为艾司西酞普兰喹硫平组(研究组)和艾司西酞普兰(对照组),每组30例,疗程为8周。在治疗前和第1,2,4,6,8周末进行汉密尔顿焦虑量表(HAMA)及临床疗效总评量表的病情严重度(CGI-SI)等评定疗效。用副反应量表(TESS)、心电图(ECG)检查、实验室检查评定安全性。结果 与治疗前比较,2组在第8周末HAMA、CGI-SI评分均显著下降(P<0.05);第1周末,研究组显著下降(P<0.05),对照组下降无统计学差异。组间HAMA比较有统计学意义(P<0.05)。CGI-SI在第1,2,4周末比较有统计学意义(P<0.05)。研究组和对照组治疗有效率分别为86.7％和70％,差异有统计学意义(P<0.05);不良反应发生率分别为20.0％和23.3％,差异无统计学意义。结论 喹硫平联用艾司西酞普兰治疗广泛性焦虑障碍疗效确切、起效快、不良反应轻。     

奥沙西泮与劳拉西泮治疗广泛性焦虑症的对照研究

目的 研究奥沙西泮与劳拉西泮治疗广泛性焦虑的临床疗效和安全性.方法 回顾性分析广泛性焦虑障碍120例,随机分为两组,奥沙西泮组和劳拉西泮组,各60例,比较两组治疗后的临床疗效,以及评定治疗期间的不良反应发生率.结果 奥拉西泮组临床治疗有效率高于劳拉西泮组,差异有统计学意义(P<0.05);两组治疗期间所发生的不良反应比率差异均无统计学意义(P>0.05);奥拉西泮组治疗后肝功能异常低于劳拉西泮组.差异有统计学意义(P<0.05).结论 奥沙西泮治疗广泛性焦虑症,临床疗效优于劳拉西泮,对肝功能影响小,安全性更高.     

加味酸枣仁合剂治疗广泛性焦虑症对照研究

目的:观察加味酸枣仁合剂治疗广泛性焦虑症的临床疗效和安全性。方法:将195例广泛性焦虑症患者随机分为研究组(加味酸枣仁合剂治疗)98例和对照组(阿普唑仑治疗)97例,疗程6周,于疗前、及治疗后第1、2、4、6周末采用Hamil- ton焦虑量表(HAMA)和副反应量表(TESS)评定疗效和不良反应。结果:两组疗效相似,加味酸枣仁合剂组总有效率为65．3％;阿普唑仑组总有效率69．1％,两组无统计学差异;加味酸枣仁合剂的不良反应以胃肠道症状为主,阿普唑仑的不良反应以嗜睡为主。结论:加味酸枣仁合剂用于治疗广泛性焦虑症安全有效。     

九味镇心颗粒治疗广泛性焦虑障碍疗效观察

目的：探讨九味镇心颗粒治疗广泛性焦虑障碍的疗效与安全性。方法：112例广泛性焦虑障碍患者随机分为研究组和对照组,每组56例,分别给予九味镇心颗粒和帕罗西汀治疗,疗程6周。采用汉密尔顿焦虑量表（HAMA）观察两组疗效,采用副反应量表（TESS）观察两组药品不良反应。结果：两组治疗后2周HAMA评分均较前明显下降（P〈0.01）,治疗前、后各时间点两组间HAMA评分比较,差异无统计学意义（P〉0.05）。两组治愈率、有效率比较,差异均无统计学意义（P〉0.05）。研究组不良反应发生率为14.8%,低于对照组的22.6%（P〈0.05）,两组TESS总分比较,差异无统计学意义（P〉0.05）。结论：九味镇心颗粒治疗广泛性焦虑障碍疗效与帕罗西汀相仿,但不良反应较少,安全性好。     

西酞普兰与阿普唑仑治疗广泛性焦虑症的Meta分析

目的：评价西酞普兰与阿普唑仑治疗广泛性焦虑症的疗效及安全性。方法：根据关键词检索出2000～2010年的文献,对入选合格的文献进行Meta分析。结果：共有8篇文献,包括557例患者。在治疗广泛性焦虑症结束后HAMA和SAS评分比较上,西酞普兰明显优于阿普唑仑（P〈0．05）,而两者临床显效率和有效率差异无统计学意义。在锥体外系反应和嗜睡的不良反应发生率上,西酞普兰明显低于阿普唑仑（P〈0．05）;在胃肠道反应和口干的不良反应发生率上,阿普唑仑明显低于西酞普兰（P〈0．05）;两者其他不良反应发生率上差异无统计学意义。结论：西酞普兰与阿普唑仑均是治疗广泛性焦虑症的良好药物,不良反应有明显不同,但在中长期治疗中西酞普兰明显优于阿普唑仑。     

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety- and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery.     

Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder

Patients with generalized social anxiety disorder (GSAD) exhibit heightened activation of the amygdala in response to social cues conveying threat (eg, fearful/angry faces). The neuropeptide oxytocin (OXT) decreases anxiety and stress, facilitates social encounters, and attenuates amygdala reactivity to threatening faces in healthy subjects. The goal of this study was to examine the effects of OXT on fear-related amygdala reactivity in GSAD and matched healthy control (CON) subjects. In a functional magnetic resonance imaging study utilizing a double-blind placebo-controlled within-subjects design, we measured amygdala activation to an emotional face matching task of fearful, angry, and happy faces following acute intranasal administration of OXT (24 IU or 40.32 μg) and placebo in 18 GSAD and 18 CON subjects. Both the CON and GSAD groups activated bilateral amygdala to all emotional faces during placebo, with the GSAD group exhibiting hyperactivity specifically to fearful faces in bilateral amygdala compared with the CON group. OXT had no effect on amygdala activity to emotional faces in the CON group, but attenuated the heightened amygdala reactivity to fearful faces in the GSAD group, such that the hyperactivity observed during the placebo session was no longer evident following OXT (ie, normalization). These findings suggest that OXT has a specific effect on fear-related amygdala activity, particularly when the amygdala is hyperactive, such as in GSAD, thereby providing a brain-based mechanism of the impact of OXT in modulating the exaggerated processing of social signals of threat in patients with pathological anxiety.     

坦度螺酮联合九味镇心颗粒治疗广泛性焦虑的临床研究

摘 要 目的： 观察九味镇心颗粒治疗广泛性焦虑的有效性及安全性。方法: 广泛性焦虑诊断患者按入院先后顺序分为联合用药组31例（九味镇心颗粒与坦度螺酮胶囊联用）、九味镇心组32例（单用九味镇心颗粒）、坦度螺酮组33例（单用坦度螺酮胶囊）。疗程均为4周。采用汉密尔顿焦虑量表（HAMA）分别于给药前,给药后第2、4、6周末进行评定,比较3组的临床疗效和药品不良反应。结果: 治疗第4周后,3组HAMA评分较治疗前均有明显下降（P<0.01）;治疗第6周,联合用药组HAMA评分明显低于其他两组（P<0.05）,而其他两组间差异无统计学意义(P＞0.05)。3组临床总有效率与药品不良反应发生率比较,差异均无统计学意义(P＞0.05)。结论: 九味镇心颗粒联合坦度螺酮胶囊治疗广泛性焦虑能更有效改善患者HAMA评分,疗效显著,且不增加不良反应,值得临床推广。     

九味镇心颗粒联合脑电生物反馈疗法治疗广泛性焦虑障碍的对照研究

目的:比较九味镇心颗粒联合脑电生物反馈疗法与单一的脑电生物反馈疗法治疗广泛性焦虑障碍(GAD)的临床疗效.方法:78例GAD患者随机分为两组,研究组40例予九味镇心颗粒6 g,po,tid,同时联合脑电生物反馈疗法治疗;对照组38例予单一的脑电生物反馈疗法治疗.疗程均为6周.采用汉密尔顿焦虑(HAMA)、焦虑自评量表(SAS)、临床总体印象-疗效总评量表(CGI-GI)、药物不良反应量表(TESS)评定治疗效果.结果:研究组总有效率为90.0％,对照组总有效率为68.4％,两组疗效差异有统计学意义(P＜0.01);研究组在治疗的2,4,6周末,HAMA减分率均高于对照组(P＜0.01).结论:九味镇心颗粒联合脑电生物反馈疗法治疗广泛性焦虑障碍较单一的脑电生物反馈疗法具有更好的疗效,起效较对照组快,不良反应轻微,易耐受,依从性好.     

急诊重症患者机械通气脱机后发生创伤后应激障碍的危险因素分析

目的:分析急诊重症患者于机械通气脱机后发生创伤后应激障碍(PTSD)的危险因素.方法:回顾性选择某院急诊室收治的160例重症患者为研究对象,统计患者机械通气脱机后PTSD的发生率,并以患者发生PTSD为因变量,以可能造成PTSD的相关因素(患者基线资料)为自变量,分析PTSD发生的危险因素.结果:160例患者机械通气脱...     

文拉法辛治疗焦虑症30例

目的:比较文拉法辛与丁螺环酮治疗焦虑症的疗效和不良反应.方法:将60例符合CCMD-3诊断标准的焦虑症患者随机分为文拉法辛组(30例)和丁螺环酮组(30例)治疗4周.采用汉密尔顿焦虑量表(HAMA)和副反应量表(TESS)评价疗效和副反应.结果:文拉法辛与丁螺环酮治疗焦虑症均有效,且疗效相当,不良反应均轻微.文拉法辛起效较丁螺环酮快.结论:文拉法辛是治疗焦虑症起效较快的、安全和有效的药物.     

九味镇心颗粒与坦度螺酮治疗广泛性焦虑症疗效对照

目的对比九味镇心颗粒与坦度螺酮治疗广泛性焦虑症的疗效及安全性。方法将72例符合入组标准的广泛性焦虑症患者随机分为两组,分别予以九味镇心颗粒与坦度螺酮治疗8周,采用汉密尔顿焦虑量表（HAMA）和Dtreatmentemergentsymptomscale（TESS）价疗效及不良反应。结果治疗8周后,九味镇心颗粒与坦度螺酮的显效率分别为72．22％和69．44％,两组比较无显著性差异（P〉0．05）。结论九味镇心颗粒与坦度螺酮治疗广泛性焦虑症的疗效相＂-3,均可作为治疗广泛性焦虑症的有效选择。     

Pharmacotherapy of Comorbid Mood,Anxiety, and Substance Use Disorders

Mood and anxiety disorders commonly co-occur with substance use disorders. Exploration of the neurobiology of substance use disorders and mood and anxiety disorders have found that the neural circuitry in mood, anxiety, and substance use disorders is clearly overlapping. These discoveries have encouraged the exploration of a number of pharmacotherapeutic agents in the treatment of co-occurring mood, anxiety, and substance use disorders. In this article, recent data on the pharmacotherapeutic treatment of mood and anxiety disorders in individuals with substance use disorders are reviewed. Some of the barriers to the use of pharmacotherapy in individuals with substance use disorders are discussed.     

Use of duloxetine in patients with an anxiety disorder,or with comorbid anxiety and major depressive disorder: a review of the literature

Importance of the field: Except for generalized anxiety disorder, few reports have been published on the efficacy, safety and tolerability of duloxetine in patients with anxiety disorders individually or in comorbidity with major depressive disorder (MDD).

Areas covered in this review: The literature search in Medline (dating back to 1966) and Embase (dating back to 1988) databases was conducted using the OVID interface on 9 April 2009, restricted to any article or abstract in English, per title, reporting any information on the use of duloxetine in patients with any anxiety disorder with or without concomitant MDD. A systematic review approach was taken.

What the reader will gain: The reader will gain knowledge of the current data available on the use of duloxetine to treat patients with anxiety disorders individually or in comorbidity with MDD.

Take home message: Duloxetine could be considered an effective treatment option in the treatment of anxiety disorders individually or in comorbidity with each other, or with MDD; however, apart from the well-demonstrated efficacy, tolerability and safety of duloxetine in the treatment of MDD with or without anxiety and GAD, data on this subject are preliminary and very limited, and more research is warranted.     

米氮平与氯丙米嗪治疗抑郁症伴有焦虑的临床评价

目的:比较米氮平与氯丙米嗪对抑郁症伴焦虑的疗效及其安全性。方法:111例抑郁症分为两组,米氮平组56例,男性30例,女性26例,年龄(39.4±13.7)岁,本次抑郁病期(3.4±5.2)个月,予米氮平30~45mg/d;氯丙米嗪组55例,男性29例,女性26例,年龄(40.2±12.6)岁,本次抑郁病期(4.1±3.8)个月,予氯丙米嗪100mg~200mg,1日2次,均6周为1个疗程。结果:对抑郁症状的治疗,米氮平组显效率为73.2%,丙氯米嗪组显效率为67.3%,疗效差异无显著意义(P>0.05);对焦虑症状的治疗,米氯平组显效率为78.8%,氯丙米嗪组显效率为43.6%,疗效差异有显著意义(P<0.05),整体药物不良反应发生率两组相当。结论:米氮平和氯丙米嗪是安全有效的治疗抑郁症的药物,但抗焦虑作用米氮平优于氯丙米嗪。