Risk of Suicidality in Depression with Serotonergic Antidepressants

Since depression is a risk factor for suicidal thoughts and behaviors, and since suicidal behaviors are associated with low serotonin activity, are selective serotonin reuptake inhibitors (SSRIs) more effective than other antidepressants in treating suicidality in depressed patients? There is inconclusive evidence for and against this hypothesis. However, all studies suggest that antidepressants are effective treatments of suicidal ideations and behaviors, and SSRIs have been shown to have prophylactic effects in preventing suicidal behaviors. Although some reports suggest that SSRIs might increase suicidal ideations and behaviors, the results of large, double-blind studies do not suggest a causal relationship between pharmacotherapy and the emergence of suicidality. Undertreatment of depression and therapeutic failure are more significant problems with the use of antidepressants in suicidal patients than the risk of using antidepressants in overdose. Prescribing inadequate doses of antidepressants is therefore a source of overlooked risk.     

中枢5-HT能系统在早发性抑郁中的作用研究

早发性抑郁的发病机制尚不明确。现仅有选择性5-HT重摄取抑制剂(selective serotonin reuptake inhibitors,SSRIs)SSRIs批准用于临床治疗早发性抑郁,显示出五羟色胺(5-hydroxytryptamine/serotonin,5-HT)5-HT是早发性抑郁发病机制中最重要的神经递质。目前有关中枢5-HT能系统在早发性抑郁中的作用研究主要集中在5-HT合成不足、5-HT运输功能障碍等方面,并与5-HT能系统较早发育成熟有关。色氨酸吸收障碍以及5-HT合成障碍都会导致5-HT合成不足;同时,5-HT转运体蛋白(5-HTT)基因多态性位点5-HTTLPR低转录效率基因型可能会增加早发性抑郁的患病风险。为进一步理解中枢5-HT能系统在早发性抑郁中的作用,未来需要进行更广泛更深入的基础及临床研究。     

阿戈美拉汀与SSRIs治疗抑郁症的效果及安全性网状Meta分析

目的 采用网状Meta分析的方法评价阿戈美拉汀与选择性5-羟色胺再摄取抑制剂（SSRIs）治疗抑郁症的效果及安全性。方法 计算机检索中国知网（CNKI）、万方数据知识服务平台、维普数据库（VIP）、中国生物医学文献数据库（CBM）、PubMed、Embase和Cochrane Library数据库,检索时限为建库至2021年11月,两名研究员独立按照纳入及排除标准对检索文献进行筛选、质量评价和数据提取。采用ADDIS进行统计分析。结果 共纳入22项随机对照试验,共7 256例抑郁症患者。网状Meta分析结果显示,依据贝叶斯统计学方法对一致性分析结果排序,在治疗效果方面,艾司西酞普兰（P=0.63）在有效率指标中成为最佳治疗措施的概率最高,帕罗西汀（P=0.31）在治愈率指标中成为最佳治疗措施的概率最高;在安全性方面,帕罗西汀（P=0.44）成为不良事件发生率最高的治疗措施的概率最高,舍曲林（P=0.74）成为中途退出研究的患者人数最多的治疗措施的概率最高。结论 在治疗抑郁症的效果方面,艾司西酞普兰与帕罗西汀可能优于舍曲林、阿戈美拉汀、西酞普兰和氟西汀;在安全性方面,帕罗西汀和舍曲林可能最差。     

暴露反应阻止对5-羟色胺再摄取抑制剂抵抗强迫症患者疗效的影响

目的：了解暴露反应阻止疗法对5‐羟色胺再摄取抑制剂治疗无效强迫症患者临床疗效的影响。方法对36例5‐羟色胺再摄取抑制剂治疗无效的强迫症患者予以暴露反应阻止疗法治疗,观察15周。于治疗前后采用 Yale‐Brow n强迫症状量表及症状自评量表评定临床疗效。结果治疗15周末,本组患者总有效率为72．2％,Yale‐Brow n强迫症状量表总分及强迫思维、强迫行为因子分和症状自评量表总均分及各因子分均较治疗前显著降低（P＜0．01）。结论暴露反应阻止疗法对5‐羟色胺再摄取抑制剂治疗无效的强迫症患者临床疗效显著,且能显著改善患者的精神状况,值得临床推广应用。     

Antidepressant-like effect of the methanolic extract from Bupleurum falcatum in the tail suspension test

In traditional Oriental medicine, some herbal combinations that include Bupleurum falcatum (BFM) as a major ingredient are known to effectively treat depressive-like disorders. In the present study, the antidepressant-like effect of methanolic extract of BFM and its neuropharmacological mechanism were investigated in mice. After oral administration of BFM extract, a tail suspension test (TST) and open field test (OFT) were performed to assess the antidepressant activity and psycho-stimulant side-effects, respectively. Pre-treatment with p-chlorophenylalanine (PCPA, a serotonin synthesis inhibitor) and α-methyl-p-tyrosine (AMPT, a catecholamine synthesis inhibitor) was used to assess the influence of BFM extract on the antidepressant activity in the TST. At doses of 150 and 300 mg/kg body weight, p.o., the BFM extract significantly reduced the total duration of immobility in the TST, while individual differences in locomotor activities between experimental groups were not observed in the OFT. Moreover, pre-treatment with PCPA (100 mg/kg i.p., for 4 consecutive days) or AMPT (100 mg/kg i.p.) significantly inhibited the antidepressant-like activity of BFM extract (300 mg/kg p.o.), as well as we confirmed the reversal of the antidepressant effect of fluoxetine (30 mg/kg i.p.) by PCPA and bupropion (20 mg/kg i.p.) by AMPT in the TST. Taken together, these findings suggest that the methanolic BFM extract has dose-dependent possibility of antidepressant-like activity valuable to alternative therapy for depression and that the mechanism of action involves the serotonergic and noradrenergic systems although underlying mechanism still remains to be further elucidated.     

Association between obsessive-compulsive disorder and a variable number of tandem repeats polymorphism in intron 2 of the serotonin transporter gene

BACKGROUND: Pharmacological studies indicate a dysregulation of the serotonergic system in obsessive-compulsive disorder (OCD). A variable number tandem repeats (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been described in intron 2 of the serotonin transporter (5-HTT) gene. This polymorphism has been associated with unipolar depression, bipolar disorder, schizophrenia, and anxiety disorders including OCD. METHODS: The association between OCD and the polymorphism is examined in 97 OCD patients, 578 psychiatric controls and 406 healthy controls, all Spanish Caucasians. RESULTS: Genotype frequencies for the polymorphism were significantly different in OCD patients, psychiatric patients and controls. There was a significant excess of 12/12 and 12/10 genotypes in OCD patients compared to psychiatric patients and controls. CONCLUSIONS: Our results indicate a possible association between the Stin2.12 allele of the VNTR polymorphism and OCD.     

Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives?

The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people’s mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19.     

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.