Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial

BACKGROUND: Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder. METHODS: Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6. RESULTS: Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0.001). There was no statistically significant difference between the mean +/- SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (> or = 50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of < or = 7). None of the differences in reported adverse events was statistically significant. CONCLUSION: In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder.     

抑郁症和糖尿病共病患者的临床特征对照研究

目的探讨抑郁症和糖尿病共病患者的临床特征。方法使用自制调查表,收集30例抑郁症和糖尿病共病患者和30例单纯抑郁症患者的社会人口学资料和病情资料。结果抑郁症和糖尿病共病患者的平均病程、平均发病次数和平均住院日均显著高于单纯抑郁症患者;抑郁症和糖尿病共病患者的临床症状显著重于单纯抑郁症患者;抑郁症和糖尿病共病患者的出院疗效显著差于单纯抑郁症患者。结论抑郁症和糖尿病共病患者的临床症状重、治疗难度大。     

Duloxetine 60 mg once daily in the treatment of milder major depressive disorder

There is ongoing debate regarding the effectiveness of antidepressants in patients with milder major depressive disorder (MDD). This post-hoc analysis evaluated the efficacy and tolerability of duloxetine in the subset of 159 (75 duloxetine and 84 placebo) patients with milder MDD (baseline HAMD17 total score > or = 15 and < or = 18) who were treated once daily with duloxetine 60 mg or placebo in two identical, 9-week, randomised, double-blind trials. At endpoint, change from baseline on HAMD17 was greater in the duloxetine group (-7.0) than in the placebo group (-4.1) (p = 0.005). Response and remission rates, and improvement on the Clinical Global Impressions-Severity (CGI-S) scale, the Patient Global Impressions-Improvement (PGI-I) scale, and measures of painful symptoms were also significantly better in the duloxetine group (p < 0.05). Tolerability was consistent with that seen in previous studies of duloxetine in patients with more severe depression. In conclusion, duloxetine 60 mg/day is effective and well tolerated in milder MDD.     

神经影像揭示重度抑郁症的神经回路和肠道微生物群的复杂相互作用

重度抑郁症是一类预后不佳的精神疾病,但它的发病机制尚未完全阐明。磁共振成像的发展为揭示其神经病理机制并明确其客观诊断依据奠定了基础,且越来越多的证据表明重度抑郁症与微生物群-肠-脑轴功能障碍之间存在密切关联。神经影像和测序技术的进步使得探索大脑、肠道和微生物组之间的相互作用变得越来越可行,针对神经影像和肠-脑相互作用的研究将为揭示抑郁症背后的病理机制以及构建针对抑郁症的肠道介导疗法提供一个更加精准的视角。本综述将对重度抑郁症的脑影像研究现状、肠道微生物与重度抑郁症的关系以及脑影像与肠-脑相互作用之间的研究进展进行归纳阐述。     

S-氯胺酮治疗重度抑郁症疗效、安全性观察及机制讨论

目的本研究目的是观察S-氯胺酮治疗重度抑郁症（MDD）疗效、安全性,并初步探讨S-氯胺酮抗抑郁及可能的急性副反应的机制。 方法采用治疗前后对照的方法,于2020年10月至2021年12月在无锡市精神卫生中心临床心理科、无锡市中医医院临床心理科以及安徽医科大学附属巢湖医院精神科招募首发或复发的MDD患者40例,受试者入组后被随机归入使用S-氯胺酮联合抗抑郁药治疗组（研究组,20例）和生理盐水加抗抑郁药组（对照组,20例）。S-氯胺酮按0.4 mg/kg单次静脉微量泵缓慢注射给药。分别在S-氯胺酮或生理盐水给药前、给药后24 h、1周末、4周末时采用蒙哥马利抑郁评定量表（MADRS）等评估患者症状;采用6项临床解离症状量表评估患者解离症状。采用重复测量方差分析比较研究组和对照组治疗前后症状评分差异,当P＜0.05时,认为差异具有统计学意义。 结果研究组和对照组经治疗均出现MARDS评分下降趋势,并且2组存在分组差异（P＜0.05）;研究组评分在24 h,1周末和4周末时均优于对照组,其中24 h差异最显著。在S-氯胺酮给药24 h后,有5例患者（25%）达到了完全缓解（MADRS≤10）,另有5例患者达到有效缓解（MARDS降分≥30%）,9例患者部分缓解。 结论S-氯胺酮是一种快速、有效、安全的新型抗抑郁药,单次小剂量静脉用药也有较好的疗效。     

The effect of adherence therapy on medication adherence,health beliefs,self-efficacy,and depressive symptoms among patients diagnosed with major depressive disorder

Medication adherence is a crucial health issue in major depressive disorder (MDD) that requires regular monitoring and attention. Hence, there are multiple reasons for medication non-adherence among them. This study aimed to examine the effect of adherence therapy (AT) on medication adherence, health beliefs, self-efficacy, and depressive symptoms among patients diagnosed with MDD. One group pretest-posttest, repeated measures time-series design was conducted. A sample of 32 patients was recruited conveniently; they received eight weekly sessions of AT. A self-reported questionnaire was used to measure variables. The analysis showed that the mean scores of the baseline indicated non-adherence, moderate general benefits beliefs about the medication, high beliefs that medication is harmful, high beliefs that doctors overuse medication, high beliefs about potential adverse effects from medication, low perception of MDD severity, and high threatening perception regarding MDD, a moderate degree of confidence in the ability to taking medications, and patients had moderately severe depressive symptoms (M = 16, 3.2, 3.1, 4.1, 3.8, 50, 3, 16 respectively). Over four measurement points, adherence therapy enhanced positive beliefs towards taking medication and illness, increased medication adherence self-efficacy, improved medication adherence, and decreased depressive symptoms (F = 68.57–379.2, P < 0.001). These improvements were clinically significant in all variables immediately post-AT but declined minimally over time. The study indicated that integrating AT as part of the pre-discharge protocol is one core component to sustaining positive healthcare outcomes. Continuous efforts should be paid in terms of the long-term sustainability of an intervention to enhance adherence and clinical outcomes.     

重型抑郁症患者脑网络性别差异的功能磁共振成像研究进展

重型抑郁症存在显著的性别差异已经得到广泛的研究证实。基于磁共振成像的脑网络分析方法已经在重型抑郁症性别差异的临床医学研究中被普遍用于疾病的神经机制和诊疗研究,已有许多临床研究成果能为临床疾病的病理探究和辅助诊断提供更好的依据。笔者通过归纳总结几种最常用脑网络研究方法,综合论述了基于磁共振成像在重型抑郁症性别差异的研究进展及应用前景。     

Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: A randomized double-blind placebo-controlled trial

BackgroundObsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that is causally linked to dysregulation of the serotonergic system. The aim of this study is to investigate the efficacy of Withania somnifera (W. somnifera) root extract as an adjunct therapy to standard OCD treatment.MethodsThirty patients with a confirmed diagnosis of OCD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria participated in this randomized double-blind placebo-controlled trial and were randomly assigned to the treatment group (W. somnifera extract, 120 mg/day; n = 15) or the placebo group (n = 15). All patients were under treatment with Selective Serotonin Re-uptake Inhibitors (SSRIs), and were instructed to take 4 capsules of the extract or placebo per day, preferably after meals, for a period of six weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used in order to assess the severity of OCD symptoms at baseline and at the end of the trial. Statistical analyses were performed using SPSS software and Y-BOCS values were presented as median and range (Min-Max).ResultsComparison of the change in Y-BOCS score during the course of the trial revealed a significantly greater effect of W. somnifera (26 (14–40) [pre-treatment] versus 14 (4–40) [post-treatment]; change: −8 (−23 to 0)) versus placebo (18 (11–33) [pre-treatment] versus 16 (10–31) [post-treatment]; change: −2 (−4 to 0)) (P < 0.001). The extract was safe and no adverse event was reported during the trial.ConclusionW. somnifera extract may be beneficial as a safe and effective adjunct to SSRIs in the treatment of OCD.     

重性抑郁障碍患者事件相关电位P300特征分析

目的 探讨伴自杀风险的重性抑郁障碍患者听觉事件相关电位(auditory evoked potential,AEP)P300(P3)特征.方法 研究组为62例重性抑郁障碍患者,其中有自杀风险的抑郁患者25例为研究组Ⅰ,无自杀风险患者37例为研究组Ⅱ.对照组为62例健康体检者;对所有研究者进行AEP P3检测,并进行对比分析.结果 研究组患者AEP P3波潜伏期较对照组明显延长,(308.76±26.11)ms vs(287.53±11.45)ms(t=5.860,P＜0.01);研究组Ⅰ患者N2、P3波幅比研究组Ⅱ患者显著降低,N2(2.75±1.71)mV vs(3.96±1.82)mV(t=2.630,P＜0.01); P3(4.14±1.78)mV vs(6.98±2.13)mV(t=5.500,P＜0.01).结论 AEP P3可用于评定重性抑郁障碍患者的认知功能损害,并可作为评价抑郁患者自杀风险的参考指标.     

Electroconvulsive therapy plays an irreplaceable role in treatment of major depressive disorder

Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide. Electroconvulsive therapy is the oldest and most effective treatment available for the treatment of severe major depressive disorder. Electroconvulsive therapy modifies structural network changes in patients with major depressive disorder and schizophrenia. And it can also affect neuroinflammatory responses and may have neuroprotective effects. Electroconvulsive therapy plays an irreplaceable role in the treatment of major depressive disorder.     

Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial

The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia.     

Comparative pain and mood effects in patients with comorbid fibromyalgia and major depressive disorder: Secondary analyses of four pooled randomized controlled trials of duloxetine

The objective of this paper is to better understand the relationship of pain and mood in patients with fibromyalgia and comorbid major depressive disorder (MDD). Pooled data from 4 double-blind, placebo-controlled, randomized trials of duloxetine hydrochloride 60-120 mg/day in patients with fibromyalgia were included (N = 1332). Of these, 350 (26% [147 placebo, 203 duloxetine]) had comorbid MDD (per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and were included in these analyses. Primary measures included Brief Pain Inventory average pain; Hamilton Depression Rating Scale or Beck Depression Inventory. Logistic regression was used to evaluate the consistency of treatment effect across various subgroups. Path analysis was used to assess the effect of duloxetine on improvement in pain in the presence of improvement in mood and vice versa. Results indicated that 69% of improvement in pain was a direct effect of treatment, with improvement in mood accounting for 31% of pain response. In conclusion, consistent with our hypothesis, duloxetine produced a substantial direct effect on pain improvement and change in mood exerted a modest indirect effect on pain improvements in patients with fibromyalgia and MDD. Hence, both direct and indirect analgesic and antidepressant properties appear to be relevant for the treatment of these comorbid patients with duloxetine.     

瑞波西汀治疗重性抑郁障碍对照研究

目的探讨瑞波西汀治疗重性抑郁障碍的临床疗效与安全性。方法将66例重性抑郁障碍患者随机分为研究组35例口服瑞波西汀治疗,对照组31例口服氟西汀治疗,观察6w。于治疗前及治疗2w、4w、6w末采用汉密顿抑郁量表、汉密顿焦虑量表评定临床疗效,临床疗效总评量表评定病情严重程度,副反应量表评定不良反应。结果治疗6w末,研究组有效率85．7％,对照组为64．5％,研究组有效率显著高于对照组（χ2=4．02,P〈0．05）。两组治疗后汉密顿抑郁量表、汉密顿焦虑量表、临床疗效总评量表总分均较治疗前有显著性下降,并随着治疗时间的延续均呈持续性下降;研究组治疗4W、6w末均较对照组下降显著（P〈0．05或0．01）。两组不良反应均轻微,研究组发生率22．9％,对照组发生率为25．8％,两组差异无显著性（χ2=0．08,P〉O．05）。结论瑞波西汀与氟西汀治疗重性抑郁障碍均有效,但瑞波西汀疗效、安全性高、依从性优于氟西汀。     

Comparison of SSRIs and SNRIs in major depressive disorder: a meta‐analysis of head‐to‐head randomized clinical trials

Context: Controversy exists whether serotonin–norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs). Objective: To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure. Data sources: Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007. Study selection: Included studies were those head‐to‐head randomized trials comparing remission (HAMD‐17 ≤7–8, MADRS ≤10–12) after 8–12 weeks of therapeutic doses of SSRIs or SNRIs in patients diagnosed with MDD were targeted for analysis. Reviews, letters, commentaries, economic studies, etc. were excluded. Studies were reviewed by two independent researchers. Where disagreements occurred in study selection, a consensus approach was used. Data extraction and analysis: Targeted outcome data included number of patients achieving remission, withdrawing from therapy due to lack of efficacy (LoE) and/or adverse drug reactions (ADRs), and total patients in trial. A random effects model combined intent‐to‐treat (ITT) and per‐protocol (PP) odds ratio (OR), and remission and dropout rates. Chi‐square assessed heterogeneity. Quality assessment was done using Downs‐Black checklist. Results: Thirty‐three studies were identified; 18 were rejected (patients had co‐morbidities in 7, outcomes differed in 5, different follow‐up in 3, and three reviews). Fifteen head‐to‐head trials of 3094 patients, average age was 41·9 ± 11·9 years (for SNRIs) and 41·6 ± 12·1 years (for SSRIs), P = 0·941. All analyses displayed non‐heterogeneity (P > 0·05). The OR (under ITT) was 1·27 (1·06–1·52 95% CI) favoring SNRIs. Meta‐analytic remission rates were 48·5 ± 3·2% and 41·9 ± 4·2% for SNRIs and SSRIs, respectively. The meta‐analytic difference in remission rates between drugs was 5·7% (P = 0·007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3·2% difference, P < 0·001). Dropout rates due to LoE were non‐significant between studied groups (P > 0·05). Conclusions: Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.     

口服国产司帕沙星片治疗急性细菌性感染多中心随机对照研究

目的评价国产司帕沙星片治疗急性细菌性感染的临床疗效与安全性.方法以国产洛美沙星片为对照药进行随机对照研究,共治疗各种细菌性感染231例,其中司帕沙星组117例、洛美沙星组114例.司帕沙星200～300mg,每日1次口服,疗程5～14d;洛美沙星300mg,每日2次口服,疗程5～14 d.结果司帕沙星组与对照组的痊愈率和有效率分别为84.62%与74.56%和94.87%与92.98%.细菌清除率分别为94.28%和92.02%.组间比较差异无显著性(P＞0.05).两组的不良反应发生率分别为7.69%和11.40%(P＞0.05),反应多呈轻度,勿需处理可自行缓解.结论司帕沙星抗菌谱广,抗菌活性强,为治疗中、轻度急性细菌性感染安全有效的口服抗菌药物.     

Stress-evoked opioid release inhibits pain in major depressive disorder

To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the mu-opioid antagonist naltrexone (50mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-min interval, began a 25-min arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold- and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, mu-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.