文拉法新、瑞波西汀对五羟色胺回吸收抑制剂治疗后达不到完全缓解抑郁症的疗效

目的 研究文拉法新和瑞波西汀对经五羟色安回吸收抑制剂(SSRIs)治疗达不到完全缓解的抑郁症患者的疗效和副反应.方法 收集经SSRIs治疗8周达不到完全缓解的抑郁症患者117例,随机分成3组,分别给予文拉法新、瑞波西汀和继续维持原药和原剂量继续治疗8周.于患者入组前和入组后1,2,4,6,8周末用汉密尔顿抑郁量表(HAMD)和副反应量表(TESS)评定疗效和副反应,并于入组前和入组治疗后4、8周末检查血压、血糖、血常规、尿常规和心电图.结果 文拉法新组和瑞波西汀组患者在治疗4周末[分别为(18.8±5.5)分和(19.3±5.8)分]、8周末[分别为(12.7±3.3)分和(14.5±3.7)分]HAMD量表的评分显著低于原药组[4周末(22.7±6.2)分,8周末(19.3±6.0)分]( F =3.93,6.79,P <0.05).治疗8周末,文拉法新组HAMD量表的评分显著低于瑞波西汀组( F =6.79,P <0.05).文拉法新和原药组患者治疗2周后[分别为(24.5±6.3)分和(24.3±7.1)分]HAMD评分较治疗前[分别为(28.2±9.5)分和(28.5±9.7)分]有显著下降( t =2.7,2.1,P <0.05),瑞波西汀组患者治疗4周末才显著下降( t =4.8,P <0.01).治疗结束时文拉法新和瑞波西汀组患者的认知障碍[分别为(4.8±2.3)分和(4.1±1.9)分]、迟缓[分别为(4.4±1.9)分和(3.4±1.7)分]和绝望感[分别为(1.7±0.8)分和(1.5±0.7)分]因子减分显著高于原药组[分别为(2.5±1.4)分、(1.9±1.3)分和(1.0±0.4)分]( F =5.49,10.35,6.47,P <0.05或<0.01);文拉法新组迟缓因子减分[(4.4±1.9)分]显著高于瑞波西汀组[(3.4±1.7)分]( F =10.35,P <0.05).文拉法新、瑞波西汀和原药组疗效比较差异有显著性(χ2＝9.8,P <0.05);文拉法新与瑞波西汀组疗效比较差异无显著性(χ2＝1.6,P ＞0.05),但显著优于原药组(χ2＝8.9,P <0.01);瑞波西汀与原药组比较差异无显著性(χ2＝3.7,P ＞0.05).3组副反应的发生率差异无显著性(χ2＝2.3,P ＞0.05).结论 文拉法新对SSRIs治疗达不到完全缓解的抑郁症患者有较好疗效,特别是对伴有迟滞的抑郁症患者疗效更好;文拉法新的起效时间快于瑞波西汀.     

Bleeding induced by SSRIs

Selective Serotonin Reuptake Inhibitors (SSRIs) have been accused of causing bleeding problems as a side effect. Theories about the mechanism are still being discussed. We report a case, presenting bleeding problems, during sertraline treatment. The SSRIs are widely used to treat depression and many other psychiatric disorders. Their lower severity of side effects and being markedly safer in overdose are some of the reasons of their preference as primary choice in most of the cases. Besides their common side effects like, agitation, headache, insomnia, weight gain or loss, and sexual dysfunction, SSRIs also have been suspected of increasing the risk of bleeding. A population-based cohort study supported the hypothesis of an increased risk of upper gastrointestinal bleeding during the use of SSRIs, and they also indicated that this effect is potentiated with concurrent use of NSAIDs or low-dose aspirin. We would like to report our recent experience with one patient who was on sertraline, 50 mg/day.     

针刺联合西药对初发抑郁障碍患者血清5-HT及TH1/TH2的影响

目的:比较针刺联合选择性5-HT再摄取抑制剂(selective serotonin reuptake inhibitors,SSRIs)与单用SSRIs对初发抑郁障碍患者抑郁缓解程度疗效差异,并探讨其对血清5-羟色胺(5-HT)及TH1/TH2失衡的影响.方法:将90例初发抑郁障碍患者随机分为针药组和药物组,每组各45例.药物组口服SSRIs,1～2次/日,连续服用4周;针药组在口服SSRIs基础上联合针刺治疗,主穴取百会、印堂、神庭、风池、大椎、四神聪,隔日1次,连续治疗4周.两组于治疗前、治疗第1、2、4周末采用汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评估患者抑郁程度.分别于治疗前、治疗4周后检测血清5-HT及白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-4(IL-4)、白介素-10(IL-10)水平,并同45例健康人作对照.结果:针药组治疗第1、2、4周末HAMD评分较治疗前降低(均P＜0.01);药物组治疗第2、4周末HAMD评分较治疗前降低(均P＜0.01),针药组治疗第1、2、4周末HAMD评分较药物组低(均P＜0.01).治疗前药物组、针药组血清5-HT及IL-4、IL-10水平均较健康组低(均P＜0.01),IL-1β、IL-6水平较健康组高(P＜0.01);针药组、药物组治疗4周后血清5-HT及IL-4、IL-10水平较治疗前升高(均P＜0.01),IL-1β、IL-6水平较治疗前降低(均P＜0.01);针药组治疗4周后血清IL-1β、IL-6水平较药物组低(均P＜0.01),血清5-HT及IL-4、IL-10水平较药物组升高(P＜0.01,P＜0.05).结论:针刺联合SSRIs治疗较单纯口服SSRIs可更快、更有效地缓解抑郁障碍患者抑郁程度,且更有利于调节血清5-HT及TH1/TH2的失衡.     

SSRIs在儿童及青少年精神障碍中的应用

目的：了解选择性5—羟色胺回收抑制剂(SSRI)类在儿童及青少年精神障碍中的应用。方法：对儿童精神科门诊使用SSRIs的75例患者进行回顾性分析。结果：SSRIs已广泛应用于治疗多种儿童及青少年精神障碍。结论：SSRIs对部分儿童及青少年精神障碍疗效较好，安全性高。     

The treatment of social phobia: a critical assessment

This article critically reviews the effects of psychological treatment (exposure, cognitive restructuring, social skills training) and pharmacological treatment (MAOIs, reversible MAOIs, anxiolytics and SSRIs) of social phobia. Only controlled studies have been included, and their outcomes were assessed for improvement in anxiety and avoidance, social functioning and clinical status. Both psychological and pharmacological treatments resulted in a significant and meaningful reduction in anxiety and, in most cases, a weakening of the tendency to avoid. Although useful, the effects were not of such a magnitude as to result in remission. Reduction in anxiety was long-lasting in patients treated by psychological methods. The lessening of anxiety did not necessarily lead to meaningfully improved social functioning. The combination of psychological and pharmacological treatments was disappointing, and did not exceed the effects of psychological treatments alone. However, the most promising medications were not tested. Subtype of social phobia and additional diagnoses did not determine the response to treatment.     

Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects

AIMS: Studies of novel centrally acting drugs in healthy volunteers are traditionally concerned with kinetics and tolerability, but useful information may also be obtained from biomarkers of clinical endpoints. This paper provides a systematic overview of CNS-tests used with SSRIs in healthy subjects. A useful biomarker should meet the following requirements: a consistent response across studies and drugs; a clear response of the biomarker to a therapeutic dose; a dose-response relationship; a plausible relationship between biomarker, pharmacology and pathogenesis. METHODS: These criteria were applied to all individual tests found in studies of selective serotonin reuptake inhibitors (SSRIs), performed in healthy subjects since 1966, identified with a systematic MedLine search. Separate databases were created to evaluate the effects of single or multiple dose SSRI-studies, and for amitriptyline whenever the original report included this antidepressant as a positive control. Doses of the antidepressant were divided into high- and low-dose ranges, relative to a medium range of therapeutic doses. For each test, the drug effects were scored as statistically significant impairment/decrease (-), improvement/increase (+) or no change (=) relative to placebo. RESULTS: 56 single dose studies and 22 multiple dose studies were identified, investigating the effects of 13 different SSRIs on 171 variants of neuropsychological tests, which could be clustered into seven neuropsychological domains. Low single doses of SSRIs generally stimulated tests of attention and memory. High doses tended to impair visual/auditory and visuomotor systems and subjective performance, while showing an acceleration in motor function. The most pronounced effects were observed using tests that measure flicker discrimination (improvement at low doses: 75%, medium doses: 40%, high doses: 43% of studies); REM sleep (inconsistent decrease after medium doses, decrease in 83% of studies after high doses); and EEG recordings, predominantly in alpha (decrease in 60% and 43% of studies after low and medium doses, respectively) and in theta activity (increase in 43% and 33% of studies after medium and high doses, respectively). Amitriptyline generally impaired central nervous system (CNS) functions, which increased with doses. Multiple doses caused less pronounced effects on the reported tests. The most responsive tests to amitriptyline appeared to be EEG alpha and theta, and REM sleep duration. CONCLUSIONS: SSRIs in healthy subjects appear to cause slight stimulating effects after low doses, which tend to diminish with dose. The most consistent effects were observed with flicker discrimination tests, EEG (alpha and beta bands), REM sleep duration, and subjective effects at higher doses. These effects are small compared with amitriptyline and other CNS-active drugs. Multiple dosing with SSRIs caused even fewer measurable differences from placebo, probably due to adaptive processes. SSRI-effects are best detected with a test battery that is sensitive to general CNS-stimulation, but such tests only comprise a very small portion of the close to 200 different methods that were found in current review.     

新的异苯骈呋喃胺类化合物的合成和抗抑郁活性初步研究

目的为进一步提高选择性5-羟色胺再摄取抑制剂（SSRIs）的选择性和抗抑郁活性,合成具有抗抑郁活性的新的异苯骈呋喃胺类化合物。方法通过三维定量构效模型成果,指导设计并合成出新的化合物,用经典抗抑郁药理试验筛选,得到新的异苯骈呋喃胺类化合物。结果新化合物合成的总收率分别为44%,51%,40%,36%,47%;药理试验结果显示,化合物4b明显减少了小鼠的静止时间,具有显著统计学意义（P〈0.05）。结论化合物4b是一种潜在的具有更高抗抑郁活性的SSRIs。     

Baseline patient characteristics associated with placebo remission and their impact on remission with duloxetine and selected SSRI antidepressants

Abstract

Objective:

We examined whether identification of patients with placebo-remitter characteristics and placebo-nonremitter characteristics enhances the ability to identify drug–placebo treatment differences and, perhaps, differences between agents in major depressive disorder (MDD). We hypothesized: 1) that drug–placebo differences in remission rates would be greater for both duloxetine and selective serotonin reuptake inhibitors (SSRIs) among placebo nonremitters than placebo remitters and: 2) that the difference between active treatments would also be greater in placebo nonremitters than placebo remitters.     

Treatment of premenstrual dysphoria with selective serotonin re-uptake inhibitors: focus on safety

Many women experience physical or mood symptoms associated with the menstrual cycle. For approximately 3 – 8% of women, the symptoms are severe enough to significantly affect social, domestic and occupational functioning. This cluster of primarily emotional and behavioural symptoms is now labelled premenstrual dysphoric disorder (PMDD). Women who meet criteria for PMDD do not usually respond to conservative interventions; selective serotonin re-uptake inhibitors (SSRIs) taken either daily or intermittently are considered to be an effective first-line therapy for this population. In this paper, the authors report on the efficacy and tolerability of SSRIs that are currently recognised as the treatment of choice for PMDD.