Histone deacetylases (HDACs) as therapeutic target for depressive disorders

Major depressive disorder (MDD) represents approximately 40% of the disability caused by mental illnesses globally. The poorly understood pathophysiology and limited efficiency of pharmacological treatment (based primarily on the principles of the monoaminergic hypothesis) make depression a serious medical, public and socio-economical problem. An increasing number of studies suggest that epigenetic modifications (alterations in gene expression that are not due to changes in DNA sequence) in certain brain regions and neural circuits represent a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of mental disorders. Accordingly, chromatin-based epigenetic regulation seems to be a promising direction for the development of new, more effective antidepressant drugs. Recently, several inhibitors of histone deacetylases (HDAC) have been extensively studied in the context of antidepressant action. So far, none of them has been used to treat depression in humans due to the low selectivity for specific HDAC isoforms, and consequently, a risk of serious adverse events. In this review, we focus on the HDAC inhibitors (HDACi) with the greatest antidepressant efficacy and their activity in the preclinical studies. Moreover, we discuss their potential therapeutic usefulness in depression and the main limitations.     

Depressive disorder and antidepressants from an epigenetic point of view

Depressive disorder is a complex, heterogeneous disease that affects approximately 280 million people worldwide. Environmental, genetic, and neurobiological factors contribute to the depressive state. Since the nervous system is susceptible to shifts in activity of epigenetic modifiers, these allow for significant plasticity and response to rapid changes in the environment. Among the most studied epigenetic modifications in depressive disorder is DNA methylation, with findings centered on the brain-derived neurotrophic factor gene, the glucocorticoid receptor gene, and the serotonin transporter gene. In order to identify biomarkers that would be useful in clinical settings, for diagnosis and for treatment response, further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed. Studies on cornerstone antidepressants, such as selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, norepinephrine, and dopamine reuptake inhibitors and their effects on depressive disorder are available, but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies. In addition, two novel drugs, ketamine and esketamine, are being investigated particularly in association with treatment of resistant depression, which is one of the hot topics of contemporary research and the field of precision psychiatry.     

Stoma Formation in Crohn’s Disease and the Likelihood of Antidepressant Use: A Population-Based Cohort Study

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Low-dose mirtazapine in treatment of major depression developed following severe nausea and vomiting during pregnancy: two cases

This report presents the successful use of low-dose mirtazapine in the treatment of major depression that developed following severe nausea and vomiting symptoms during the early gestational weeks in two cases. The psychiatric diagnosis was determined with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Assessments were performed with the Clinical Global Impression — Improvement Scale and the 17-item Hamilton Rating Scale for Depression. Further large-scale studies should be carried out to confirm the useful effects observed in these cases.     

米安色林与SSRI治疗对男性抑郁症引起的性功能障碍影响程度的差异

目的：考察米安色林与SSRI治疗对男性抑郁症引起性功能障碍的差异。方法：选择2010年2月至2013年4月本院精神科门诊治疗的男性抑郁症患者95例,随机分为两个组别,45例米安色林组,50例SSRI治疗组,治疗2个疗程,收集两个组别治疗前后的HAMD和IIEF-5评分。结果：两个组别的疗效无显著差异（P〉0．05）。两个组别治疗前和治疗2w的HAMD与治疗前的IIEF-5评分无显著差异（P〉0．05）。与米安色林组比,SSRI组治疗5～10w的HAMD和治疗2—10w的IIEF-5评分有显著差异（P〈0．05）。结论：米安色林与SSRI类抗抑郁药有着同样肯定的疗效,能够改善性功能障碍。     

联合抗抑郁药治疗功能性消化不良的临床研究

目的：探讨功能性消化不良治疗新途径及适应证。方法：将90例伴有抑郁焦虑症状的功能性消不良病人随机分为：抗消化不良组;抗抑郁组;综合治疗组,分别给予单抗消化不良治疗;单抗抑郁治疗;合并两种方法治疗。疗程均为8周。结果：三组患者的上腹胀、早饱、上腹痛、暖气症状评分、Zung自评量表分和HAMD量表评分,均较治疗前下降,但综合治疗化不请症状控制总有效率为86．7％HAMD量表评分达常模有效率为86．7％,高于抗消化不良组的36．7％和10．0％,抗抑郁组的43．3％,和16．7％,差异均有显著性。结论：伴有抑郁焦虑症的功能性消化不良,在治疗时联合使用抗抑郁药,能明显提高临床疗效。     

抗抑郁药用于疼痛治疗的研究进展

慢性痛或神经痛是一种临床综合征,常伴有抑郁障碍,严重影响患者生活质量.对于神经痛,常规镇痛药物、甚至麻醉性镇痛药经常无效,而抗抑郁药、抗精神病药和抗癫痫药物等则有效.本文综述了抗抑郁药用于镇痛的作用机制和不同类型的抗抑郁药在疼痛治疗中的应用,旨在为疼痛的临床治疗提供参考.     

Depression treatment use among stroke individuals with depression: A cross-sectional analysis of the Medical Expenditure Panel Survey

BackgroundDepression is the most prevalent psychiatric comorbidity among stroke individuals. Despite the effectiveness of antidepressants and psychotherapy, data on the use of these treatments among stroke survivors is limited.ObjectiveThe main objective of this study was to document prevalence of antidepressant use, types of antidepressants utilized, and adherence to antidepressants among stroke individuals.MethodsRetrospective, cross-sectional data obtained from the Medical Expenditure Panel Surveys (MEPS), for the years 2011, 2013 and 2015, was utilized for this study. Treatment for depression was categorized into three mutually exclusive categories: 1) antidepressants only, 2) antidepressants and psychotherapy (combination), and 3) No treatment. Adherence to antidepressants was measured using the Proportion of Days Covered (PDC) ratio. Adherence between antidepressant only and combination therapy group was compared using Student's t-test. A multinomial logistic regression analysis was used to further examine the association between patient characteristics and likelihood of receiving depression treatment.ResultsA total of 759 stroke individuals with comorbid depression were identified. Of these, 51.2% utilized only antidepressants, 12.6% utilized a combination treatment of antidepressants and psychotherapy and 31.7% did not receive treatment for depression. Selective Serotonin Reuptake Inhibitors (SSRI's) was the most commonly used antidepressants in the stroke population. Males (P = 0.04), age group of 40–64 years (P < 0.001), and African Americans (P = 0.02) constituted for the highest proportions of untreated stroke survivors. Among treated stroke individuals, adherence was higher for combination therapy users compared to those using antidepressants only (mean PDC = 65.8 ± 6.89 and 57.6 ± 3.74, respectively).ConclusionAlmost 70% of stroke individuals received some form of treatment for depression and several patient-related factors (gender, age, race, marital status, and comorbidity burden) were associated with the utilization of depression treatment. Future researchers need to investigate the factors responsible for lack of depression treatment in stroke individuals and policy makers should aim for a more patient centered care.