选择性5-羟色胺再摄取抑制剂安全性研究概述

选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors，SSRIs）是广泛应用的新型抗抑郁药，用于治疗各种抑郁症。常用的SSRIs有氟西汀、帕罗西汀、舍曲林、氟伏沙明及西酞普兰。SSRIs有多种类型的不良反应，主要为胃肠道反应、停药反应、性功能障碍及抗利尿激素异常分泌综合征等。SSRIs有可能增加儿童和青少年自杀意念和行为的风险，但目前尚无定论。最新研究表明，孕妇早期服用SSRIs似乎不增加胎儿先天畸形风险，但孕妇晚期服用SSRIs，可致新生儿出现肺动脉高压和停药综合征。一般而言，用含SSRIs的母乳喂养是安全的，因其在乳汁中的含量很低，但长期服用对婴儿发育的影响尚不清楚。对于老年人，SSRIs可增加骨折风险。SSRIs和某些药物联用发生相互作用导致的不良反应如下：单胺氧化酶抑制剂：5-羟色胺综合征；利尿剂：严重低钠血症；抗凝血药：增加出血危险；非甾体抗炎药：增加上消化道出血风险；色氨酸：5-羟色胺综征；阿司咪唑、特非那定：室性心律失常，Q-T间期延长；氟哌啶醇、马普替林：严重锥体外系反应；锂盐：锂血浓度升高，毒性增加。总之，SSRIs的不良反应虽然少于三环类抗抑郁药，但其有自身特有的不良反应。因此，医师临床使用SSRIs应予以注意。     

A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis

OBJECTIVE: To examine the relative tolerability and side effect profile of tricyclic antidepressants and selective serotonin reuptake inhibitors in older depressed people. METHODS: A systematic literature search generated 37 randomised controlled trials of TCAs and SSRIs of which 11 were entered into a meta analysis comparing withdrawal rates and side effect profiles. RESULTS: 537 TCA recipients and 554 SSRI recipients were compared. TCAs had an increased withdrawal rate (RR: 0.24, CI 1.04, 1.47). A similar result was found when comparing classical TCAs (451 patients) (amitriptyline, clomipramine, doxepin and dothiepin) with SSRIs (466 patients) (RR 1.30 CI: 1.02,1.64). These findings were reflected in the increased TCA prevalence of side effects including dry mouth, drowsiness, dizziness and lethargy. No differences were found when comparing TCA related drugs (mianserin and trazadone) with SSRIs (RR 1.07 CI 0.43, 2.70). CONCLUSIONS: Despite the relative low prevalence of side effects associated with SSRIs a significant minority of older people find these drugs intolerable and experience nausea, vomiting, dizziness and drowsiness. We conclude that TCA related drugs are comparable to SSRIs in terms of tolerability and may offer an alternative when SSRIs are either contra-indicated or clinically unacceptable.     

Delayed mood transitions in major depressive disorder

The hypothesis defended here is that the process of mood-normalizing transitions fails in a significant proportion of patients suffering from major depressive disorder. Such a failure is largely unrelated to the psychological content. Evidence for the hypothesis is provided by the highly variable and unpredictable time-courses of the depressive episodes.     

A benzisothiazole derivative and antipsychotic agent,perospirone, for augmentation of selective serotonin reuptake inhibitors (SSRIs) in refractory obsessive-compulsive disorder (OCD): two patient case series

Even though selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharamacological treatment for obsessive-compulsive disorder (OCD), as many as 40% of patients do not have an adequate response to these medications. For such SSRI-refractory patients, the augmentation of SSRIs with new-generation antipsychotics that modulate both 5-HT and DA systems has recently been proven effective in controlled augmentation studies. The benzisothiazole derivative perospirone is a new serotonin 5-HT2 and dopamine D2 antagonist available in Japan for the treatment of schizophrenia. As its unique property, perospirone also exhibits 5-HT1A agonistic action. We present two SSRI-refractory OCD patients who showed little improvement with adequate trials of SSRI monotherapy, but exhibited significant improvement in their OCD symptoms after the addition of perospirone to ongoing SSRI treatment. The cases suggest that perospirone augmentation may be an effective and well-tolerated strategy for SSRI-refractory OCD patients. Controlled studies are required to further confirm the efficacy and tolerability of perospirone augmentation for treatment-resistant OCD.     

2013—2017年江苏省荣军医院选择性5-HT再摄取抑制剂类抗抑郁药的使用情况分析

目的 分析江苏省荣军医院2013-2017年选择性5-HT再摄取抑制剂（SSRIs）类抗抑郁药的使用情况,为临床合理用药和优化药品管理提供参考。方法 收集江苏省荣军医院2013-2017年SSRIs的使用资料,利用Excel对药品金额、用药频度（DDDs）、日均费用（DDC）、药品排序比值（B/A）等进行分析。结果 2013-2017年SSRIs类抗抑郁药的销售金额呈上升趋势,艾司西酞普兰、舍曲林的销售金额与DDDs一直处于前列,氟伏沙明增长幅度最快。艾司西酞普兰的DDC相对较高,舍曲林和氟伏沙明的DDC相对较低。氟伏沙明的B/A值较高,其余各药物的B/A值接近于1。结论 2013-2017年江苏省荣军医院SSRIs类抗抑郁药的应用基本合理,药品的疗效是影响临床应用的关键,同时药物的经济性也是重要因素。     

5-羟色胺再摄取抑制剂联合胰岛素治疗躯体形式障碍对照研究

目的探讨高选择性5羟色胺再摄取抑制剂联合胰岛素治疗躯体形式障碍的临床疗效。方法将59例躯体形式障碍患者随机分为A组30例、B组29例，两组均口服高选择性5羟色胺再摄取抑制剂治疗，B组联合胰岛素治疗。疗程6w。于治疗前及治疗第1w、2w、4w、6w末采用汉密顿焦虑量表、汉密顿抑郁量表评定临床疗效。结果治疗6w末A组显效率53．33％，总有效率96．67％；B组分别为86．21％，100％；B组显效率显著高于A组（χ2=7．516，P〈0．01）。两组汉密顿焦虑量表、汉密顿抑郁量表评分治疗第1w末起均较治疗前有显著下降（P〈0．01），第6w末B组较A组下降显著（P〈0．05）。不良反应B组除体重增加较多外，其他因子与A组无显著性差异（P〉0．05）。结论高选择性5羟色胺再摄取抑制剂联合胰岛素治疗躯体形式障碍疗效显著，安全性高，依从性好。     

Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C/2B receptor function

Chronic treatment with selective 5-HT reuptake inhibitors (SSRI) are therapeutic in obsessive compulsive disorder, depression, anxiety, bulimia nervosa and migraine. In the present study the possibility that SSRI's act by desensitizing 5-HT_2C/5-HT_2B receptors was assessed using a putative in vivo model of 5-HT_2C/5-HT_2B receptor function, mCPP-induced hypolocomotion. mCPP (2,4 and 6 mg/kg i.p. 20 min pretest) reduced locomotion and rears in rats treated acutely or chronically with saline. Acute oral administration of the SSRI's fluoxetine (10 mg/kg), paroxetine (10 mg/kg), or clomipramine (70 mg/kg) or the noradrenaline reuptake inhibitor, desipramine (10 mg/kg), all 1 hr pretest, did not prevent mCPP-induced hypolocomotion. In contrast, chronic treatment with the SSRI's paroxetine and fluoxetine (both 10 mg/kg p.o. daily × 21 days), significantly attenuated the effect of mCPP (4 and 6 mg/kg i.p.) on locomotion and rears 24 hr after the last pretreatment dose. Chronic clomipramine (70 mg/kg p.o. daily × 21 days) also significantly attenuated the effect of mCPP (4 mg/kg i.p.) on rears and tended to reduce the hypolocomotor response. However, chronic treatment with desipramine, (10 mg/kg p.o.daily × 21) had no effect on any of the parameters measured. As chronic fluoxetine and paroxetine did not reduce brain mCPP levels (determined by HPLC 30 min after 4 mg/kg i.p.) the results suggest that chronic SSRI's, but not desipramine, reduce 5-HT_2C/5-HT/_2B receptor responsivity. If this occurs in man, it may mediate or contribute to their reported therapeutic efficacy in depression, anxiety, bulimia, migraine and alcoholism. It may also be of particular relevance to their unique efficacy in OCD.     

老年抑郁症的抗抑郁药物治疗最新进展

老年抑郁症是一种常见的慢性复发性障碍。本文综述新一代的抗抑郁药物治疗老年期抑郁的疗效、安全性以及其他相关问题。