Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

盐酸氟西汀对抑郁症模型小鼠神经肽Y表达的研究

目的 探讨盐酸氟西汀对慢性应激抑郁症模型小鼠下丘脑神经肽Y（NPY）的表达影响。方法 采用旷场试验（Open-Field）法，比较抑郁症模型小鼠与正常对照组行为学改变方面的差异。将慢性应激抑郁症小鼠模型随机分成盐酸氟西汀和阿米替林治疗组、模型对照组，同时设立空白对照组，利用半定量逆转录．聚合酶联反应（RT-PCR）法、细胞酶联免疫法和蛋白免疫印迹（Western-blot）技术，比较试验组小鼠下丘脑NPY的表达变化。结果 （1）与正常组比较，模型组在总路程缩短、活动斑数减少和体重增加幅度下降等方面具有显著性差异。（2）与正常组比较，抑郁症模型组下丘脑NPY的mRNA表迭下降。（3）经过3周的治疗，盐酸氟西汀组和阿米替林组小鼠下丘脑NPY的mRNA及蛋白表达没有明显差别，但是两组的表达结果显著高于模型对照组，与空白对照组的结果接近。结论 脑内NPY的mRNA及蛋白的表达增加可能是盐酸氟西汀治疗抑郁症小鼠的机制之一。     

郁乐疏胶囊治疗中风后抑郁的随机对照临床研究

目的:通过郁乐疏胶囊与百忧解治疗卒中后抑郁(PSD)的随机对照研究,观察郁乐疏胶囊治疗PSD的疗效和安全性。方法:将40例PSD患者在使用治疗脑卒中基础疾病的药物的同时,随机分为受试药物组(郁乐疏胶囊组)和对照药物组(百忧解组)。前者口服郁乐疏胶囊,后者口服百忧解。两组患者在治疗前及治疗后6周各进行一次HRSD量表、Zung抑郁自评量表、Barthel量表及SNSS量表评定,并观察不良反应。结果:郁乐疏胶囊组,显效率为55%,总有效率为85%。百忧解组,显效率为50%,总有效率为80%。两组药物的疗效无显著差异(P>0.05)。两组患者在治疗前后,各量表评定均无显著差异(P>0.05)。但两组患者HRSD量表中的睡眠障碍因子的评分在治疗前无显著差异(P>0.05),在治疗后有显著差异(P<0.05)。结论:郁乐疏胶囊能明显改善PSD患者的抑郁症状,促进神经功能的恢复,同时还具有改善睡眠障碍的作用。无明显不良反应,安全性较高。     

氟西汀与阿米替林治疗105例抑郁障碍病人的双盲对照试验

目的：评价国产氟西汀的抗抑郁作用及安全性。方法：采用随机、双盲对照、多中心研究，分为国产氟西汀组５７例（男性２２例，女性３５例；年龄４０±ｓ１３ａ），口服氟西汀２０ｍｇ，ｑｄ，阿米替林５７例（男性２７例，女性３０例；年龄４０±１４ａ），口服阿米替林７５ｍｇ，ｂｉｄ，疗程６ｗｋ。结果：氟西汀治疗抑郁障碍的疗效与阿米替林相当，总有效率分别为８５％及９２％（Ｐ＞０．０５）；氟西汀组的主要副作用有口干、便秘、恶心、心动过速等，但较之阿米替林程度轻且发生率低。结论：氟西汀的抗抑郁作用与阿米替林相当，副作用少，服用方便。     

氟西汀与阿米替林双盲对照治疗抑郁障碍病人16例

目的：评价国产氟西汀治疗抑郁障碍的疗效和副作用。方法：采用国产氟西汀和阿米替林双盲对照治疗１６例抑郁障碍病人。氟西汀组８例（男性３例，女性５例，年龄４５±ｓ１４ａ），用氟西汀２０ｍｇ，ｐｏ，ｑｄ。阿米替林组８例（男性３例，女性５例，年龄４４±１３ａ），用阿米替林７５ｍｇ，ｐｏ，ｂｉｄ。疗程６ｗｋ。结果：治疗后２组病人的ＨＡＭＤ，ＨＡＭＡ，ＳＤＳ评分均显著下降，显效率均为１００％，２种药物在疗效和副作用方面未有显著差异。结论：国产氟西汀是满意的新型抗抑郁剂。     

Three antidepressants (amitriptyline,dothiepin, fluoxetine), with and without alcohol,compared with placebo on tests of psychomotor ability related to car driving

Eight female volunteers received acute doses of amitriptyline 50 mg (AMI), dothiepin 50 mg (DOT), fluoxetine 40 mg (FLU) or placebo both with and without a ‘social’ dose of alcohol (ALC) equivalent to 0·5 g/kg body weight absolute alcohol. Performance on a variety of tests of psychomotor ability and cognitive function (critical flicker fusion, choice reaction time, tracking, Maddox Wing and simulated car steering) were performed at 1·5 and 4 hours following treatment. AMI and DOT both with and without ALC impaired performance on a range of tests at either or both 1·5 and 4 hours, although the effects of AMI and AMI + ALC were more widespread and severe than those found with either DOT or DOT + ALC. FLU and FLU + ALC showed no evidence of impairment on any test at either the 1·5 or the 4 hours assessments. The results suggest that there are differences between the experimental substances, at the doses used, in their intrinsic potential for impairing aspects of psychomotor performance and cognitive function.     

Moclobemide and specific serotonin re-uptake inhibitor combination treatment of resistant anxiety and depressive disorders

This retrospective study was undertaken with the objective of determining how effective and safe moclobemide, a specific and reversible inhibitor of monoamine oxidase-A (RIMA), is when used in combination with specific serotonin re-uptake inhibitors (SSRIs), in a clinical setting. A thorough chart review was done of all patients with affective and anxiety disorders seen at our centre who received combination treatment with moclobemide and an SSRI. Combination moclobemide-SSRI treatment demonstrated good efficacy in treating treatment-resistant patients. The combination treatment was well tolerated with very few drug interactions. Dosages should be started low, titrated slowly and carefully, and patients should be monitored closely.     

持续的躯体形式疼痛障碍患者抑郁症状的特征及治疗

目的：了解躯体形式疼痛障碍患者伴发的抑郁症状的特征，明确氟西汀对抑郁及焦虑症状的作用特点。方法：选取62例符合ICD－10中持续的躯体形式疼痛障碍诊断标准的患者，于治疗前及治疗第2，4，6周末评定HAMD，HAMA。疗效评定以减分率及有效率为评定指标。结果：氟西汀治疗第六周末，有效率为79．03％，治疗前及治疗第6周末的HAMD各项目分均有显著性差异（P值均＜0．01）；氟西汀治疗六周后，HAMD三个因子减分率分别为：迟滞（75．8％），焦虑／躯体性(焦虑（69．4％），体重（45．2％）；HAMA二个因子减分率分别为：精神性焦虑（70．97％），躯体性焦虑（72．58％）。结论：氟西汀对躯体形式疼痛障碍患者的抑郁及焦虑症状均有缓解作用。氟西汀对躯体疼痛障碍患者的动力缺乏亦有较好疗效。