How do antidepressants influence the BOLD signal in the developing brain?

Depression is a highly prevalent life-threatening disorder, with its first onset commonly occurring during adolescence. Adolescent depression is increasingly being treated with antidepressants, such as fluoxetine. The use of medication during this sensitive period of physiological and cognitive brain development produces neurobiological changes, some of which may outlast the course of treatment. In this review, we look at how antidepressant treatment in adolescence is likely to alter neurovascular coupling and brain energy use and how these changes, in turn, affect our ability to identify neuronal activity changes between participant groups. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), the method most commonly used to record brain activity in humans, is an indirect measure of neuronal activity. This means that between-group comparisons – adolescent versus adult, depressed versus healthy, medicated versus non-medicated – rely upon a stable relationship existing between neuronal activity and the BOLD response across these groups. We use data from animal studies to detail the ways in which fluoxetine may alter this relationship, and explore how these alterations may influence the interpretation of BOLD signal differences between groups that have been treated with fluoxetine and those that have not.     

我院2005～2007年抗抑郁药利用分析

目的：评价我院门诊患者抗抑郁药的应用现状及趋势，为临床合理用药提供参考。方法：对我院2005～2007年门诊患者使用抗抑郁药的种类、销售金额、用药频度（DDDs）等进行统计、分析。结果：抗抑郁药的处方数、购药金额及DDDs等逐年增长，5-羟色胺再摄取抑制剂（SSRI）是临床治疗抑郁症的首选药物，3年处方数比例都在80％以上。帕罗西汀、西酞普兰、氟西汀、舍曲林等SSRI在3年中都是应用最多的药物。结论：本院的抗抑郁药应用基本合理。SSRI类抗抑郁药的应用3年中占主导地位．三环类抗抑郁药（TCAs）应用较少。     

广东抗抑郁药销售市场分析

目的分析抗抑郁药在广东的销售情况和发展趋势。方法通过统计广东75家代表性医院2005-2007年抗抑郁药销售数据,了解抗抑郁药的销售情况,分析各类型抗抑郁药的销售及国内厂家与进口合资厂家药品的销售情况。结果抗抑郁药销售年均增长23.93%,5-羟色胺再摄取抑制剂（SSRIs）约占60%市场份额,进口合资药品约占87%。结论抗抑郁药销售增幅明显,SSRIs为最常用的一类抗抑郁药,国内抗抑郁药市场仍然由进口合资厂家主导,国内制药厂商迎来最好的发展机遇。     

Evidence for corticotropin-releasing factor regulation of serotonin in the lateral septum during acute swim stress: adaptation produced by repeated swimming

RATIONALE: Swim stress decreases extracellular serotonin (5-HT) levels in the rat lateral septum, and adaptation to this effect occurs with repeated swimming. Corticotropin-releasing factor (CRF) administered into the dorsal raphe nucleus (DRN) also decreases 5-HT release in the lateral septum, suggesting that CRF may mediate the effects of swim stress. OBJECTIVES: The hypothesis that endogenous CRF mediates the reduction of 5-HT levels in the lateral septum evoked by swim stress and is involved in the adaptation that occurs with repeated swim stress was tested. METHODS: Extracellular 5-HT levels in rat lateral septum were quantified by means of in vivo microdialysis. Extracellular single unit activity was recorded from the DRN. RESULTS: Intracerebroventricular (i.c.v.) administration of a CRF receptor antagonist prevented the ability of swim stress to decrease 5-HT release in the lateral septum. Prior exposure to swim stress reduced the ability of both CRF (i.c.v.) and a subsequent swim stress to decrease lateral septum 5-HT release (cross adaptation). Additionally, the effects of CRF, administered into the DRN, on DR neuronal discharge were attenuated in rats with a history of swim stress. Finally, administration of a CRF receptor antagonist (i.c.v.) between two swim stress sessions restored the neurochemical response to swim stress (i.e., 5-HT levels were reduced during the second exposure to swim). CONCLUSIONS: Endogenous CRF modulates 5-HT transmission during acute environmental stress and is also integral to adaptation of the 5-HT response produced by repeated stress. Modulation of the 5-HT system by CRF during acute stress may underlie certain coping behaviors, while stress-induced adaptation of this effect may be involved in psychiatric manifestations of repeated stress.     

Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice

We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) has antidepressive-like activity. The aim of the present study was to examine (i) whether caffeic acid, a major metabolite of rosmarinic acid, also has antidepressive-like activity, and (ii) whether these substances inhibit either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity. Rosmarinic acid (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each significantly reduced the duration of immobility in the forced swimming test in mice. In contrast, neither substance, at doses that produced a significant reduction in the immobile response in the forced swimming test, affected spontaneous motor activity. These results indicate that, like rosmarinic acid, caffeic acid also possesses antidepressive-like activity. In neuropharmacological studies, neither rosmarinic acid (10 x (-9)-10 x (-3) M) nor caffeic acid (10 x (-9)-10 x (-3) M) affected either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity in the mouse brain. These results suggest that both caffeic acid and rosmarinic acid may produce antidepressive-like activity via some mechanism(s) other than the inhibition of monoamine transporters and monoamine oxidase.     

The effects of antidepressant treatment on serotonergic and dopaminergic systems in Fawn-Hooded rats: a quantitative autoradiography study

Fawn-Hooded (FH) rats exhibit a phenotype including depressive behaviour and high alcohol preference, and as such tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) reduce alcohol consumption in this rat strain [Psychiatr. Genet. 12 (2002) 1-16]. However, the neurochemical effects of these antidepressants on monoamine systems in the brain, especially in mesolimbic areas have not been studied in FH rats. Therefore, the present study investigated neurochemical effects of subchronic treatment (10 days) with desipramine (DMI) and sertraline on several neurochemical markers of serotonin and dopamine systems. Binding to these markers including dopamine transporters (DATs), 5-HT transporters (SERTs), 5-HT(1A)- and 5-HT(2A)-receptors in rat brain sections was performed by quantitative autoradiography. The findings from the present study revealed that DMI and sertraline exhibited differential effects on SERTs and DATs in FH rat brain. For example, DMI caused a dramatic up-regulation of DATs whereas sertraline had no effect on DAT binding. In addition, both antidepressants showed some common and some differential effects on the binding to 5-HT(1A)- and 5-HT(2A)-receptors dependent upon region. These data demonstrate that DMI and sertraline differentially effect serotonergic and dopaminergic systems in mesolimbic regions in FH rats, suggesting that there may be different neurochemical mechanisms underlying their efficacy to reduce ethanol consumption in this animal model.     

Differential effects of the 5-HT2 receptor antagonist on the anti-immobility effects of noradrenaline and serotonin reuptake inhibitors in the forced swimming test

The effects of the 5-HT(2) receptor antagonist, LY 53857 on the effects of noradrenaline and serotonin reuptake inhibitors were investigated using the forced swimming test. LY 53857 enhanced anti-immobility effects of clomipramine and maprotiline, which can inhibit reuptake of noradrenaline. However, LY 53857 did not affect the immobility time of mice treated with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine. These results suggest that antagonism of the 5-HT(2) receptor leads to potentiation of the antidepressant effects of noradrenaline reuptake inhibitors but not SSRIs and that LY 53857 may modify the activity of noradrenergic neurons.     

Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression

Existing therapies for major depressive disorder (MDD) have either limited efficacy and/or poor tolerability. The present study examined the effects of duloxetine, a potent and balanced dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE), in patients with MDD. Adult patients (N=267) with MDD were randomly assigned to receive duloxetine (60 mg/day) or placebo in this 9-week, multi-center, double-blind, parallel-group clinical trial. Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD₁₇), Visual Analog Scales (VAS) for pain, Clinical Global Impression of Severity (CGI-S), Patient's Global Impression of Improvement (PGI-I), and Quality of Life in Depression Scale (QLDS). Safety was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. Duloxetine (60 mg QD) significantly reduced the HAMD₁₇ total score compared with placebo at the end of 9-week therapy. Estimated probabilities of response and remission were 65 and 43%, respectively, for duloxetine compared with 42 and 28% for placebo. Duloxetine also reduced overall pain, back pain, shoulder pain and time in pain while awake significantly more than placebo. Global measures of improvement, including PGI-I and QLDS, were significantly improved by duloxetine compared with placebo. Discontinuations due to adverse events were more frequent for duloxetine-treated patients (12.5%) than for placebo-treated patients (4.3%). Nausea, dry mouth, dizziness, and constipation were more frequent for duloxetine than placebo. There was no significant incidence of hypertension, nor any other safety issues. Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD.     

中药联合抗抑郁剂治疗早泄50例临床研究

目的：探讨中药联合小剂量抗抑郁剂治疗早泄的疗效。方法：采用分组对照的研究方法，对符合诊断标准的150例早泄患者按其意愿分为3组，每组50例。Ⅰ组给予知柏固精汤，Ⅱ组给予盐酸舍曲林，Ⅲ组给予知柏固精汤合盐酸舍曲林，均连续用药4周，分别观察患者用药前后的射精潜伏期、夫妻对性生活的满意程度和药物副作用。结果：治疗后3组患者射精潜伏期均明显延长，对性生插的满意程度均明显提高（P〈0．01），且Ⅲ组疗效优于另外两组（P〈0．01）。结论：知柏固精汤联合小剂量盐酸舍曲林治疗早泄疗效显著，明显优于单纯应用知柏固精汤或盐酸舍曲林治疗，是一种治疗早泄的有效方法。     

我国部分精神科医生关于抗抑郁治疗与转躁认识的初步调查

目的：了解我国精神科高级职称医生对双相抑郁治疗过程中抗抑郁药物与躁狂转化的认识。方法：自编与双相抑郁治疗有关的因素评价表让全国各地的专科医生根据自己的经验进行选择。结果：调查信回收率70％，有56位医生回答了全部问题。医生认为，使用抗抑郁药物(94．6％)、联合多种抗抑郁药物(64．2％)、不同时应用心境稳定剂(50．9％)与双相抑郁治疗过程中引发躁狂有关。结论：我国精神科高级职称医生对双相抑郁治疗过程中药物引起躁狂发作的认识比较全面。