Eugene Andy R
Independent Researcher, Kansas, United States of America.
Independent Neurophysiology Unit, Department of Psychiatry, Medical University of Lublin, Lublin, Poland.
PeerJ. 2020 Mar 11;8:e8748. doi: 10.7717/peerj.8748. eCollection 2020.
Sleep is one of the most essential processes required to maintain a healthy human life, and patients experiencing psychiatric illness often experience an inability to sleep. The aim of this study is to test the hypothesis that antidepressant compounds with strong binding affinities for the serotonin 5-HT2C receptor, histamine H1 receptors, or norepinephrine transporter (NET) will be associated with the highest odds of somnolence.
Post-marketing cases of patient adverse drug reactions were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) during the reporting window of January 2004 to September 2019. Disproportionality analyses of antidepressants reporting somnolence were calculated using the case/non-case method. The reporting odds-ratios (ROR) and corresponding 95% confidence interval (95% CI) were computed and all computations and graphing conducted in R.
There were a total of 69,196 reported cases of somnolence out of a total of 7,366,864 cases reported from January 2004 to September 2019. Among the 30 antidepressants assessed, amoxapine ( = 16) reporting odds-ratio (ROR) = 7.1 (95% confidence interval [CI] [4.3-11.7]), atomoxetine ( = 1,079) ROR = 6.6 (95% CI [6.2-7.1]), a compound generally approved for attention deficit hyperactivity disorder (ADHD), and maprotiline ( = 18) ROR = 6.3 (95% CI, 3.9-10.1) were the top three compounds ranked with the highest reporting odds of somnolence. In contrast, vortioxetine ( = 52) ROR = 1.3 (95% CI [1.0-1.8]), milnacipran ( = 58) ROR = 2.1 (95% CI [1.7-2.8]), and bupropion ( = 1,048) ROR = 2.2 (95% CI [2.1-2.4]) are least significantly associated with somnolence. Moreover, levomilnacipran ( = 1) ROR = 0.4 (95% CI [0.1-2.9]) was not associated with somnolence.
Among the thirty tested antidepressants, consistent with the original hypothesis, amoxepine has strongest 5-HT2C receptor binding affinity and has the highest reporting odds of somnolence. Atomoxetine, ranked second in reporting odds of somnolence overall, binds to the NET with with the strongest binding affinity among the thirty compounds. Mirtazapine, a tetracyclic antidepressant, was ranked 11th in reporting odds of somnolence and had the strongest H1 receptor binding affinity. This study provides an informative ranking of somnolence among thirty antidepressant compounds with an already wide array of clinical indications as well as provides insight into potential drug repurposing in psychopharmacology.
睡眠是维持人类健康生活所需的最基本过程之一，患有精神疾病的患者常常存在睡眠障碍。本研究的目的是检验以下假设：对5-羟色胺5-HT2C受体、组胺H1受体或去甲肾上腺素转运体（NET）具有强结合亲和力的抗抑郁化合物与嗜睡的最高几率相关。
在2004年1月至2019年9月的报告期内，从美国食品药品监督管理局不良事件报告系统（FAERS）获取上市后患者药物不良反应病例。使用病例/非病例法对抗抑郁药报告嗜睡的不成比例分析进行计算。计算报告比值比（ROR）和相应的95%置信区间（95%CI），所有计算和绘图均在R中进行。
在2004年1月至2019年9月报告的7366864例病例中，共有69196例报告的嗜睡病例。在评估的30种抗抑郁药中，阿莫沙平（n = 16）报告比值比（ROR）= 7.1（95%置信区间[CI][4.3 - 11.7]）、托莫西汀（n = 1079）ROR = 6.6（95%CI[6.2 - 7.1]）（一种通常被批准用于治疗注意力缺陷多动障碍（ADHD）的化合物）和马普替林（n = 18）ROR = 6.3（95%CI，3.9 - 10.1）是嗜睡报告几率最高的前三种化合物。相比之下，伏硫西汀（n = 52）ROR = 1.3（95%CI[1.0 - 1.8]）、米那普明（n = 58）ROR = 2.1（95%CI[1.7 - 2.8]）和安非他酮（n = 1048）ROR = 2.2（95%CI[2.1 - 2.4]）与嗜睡的关联最不显著。此外，左旋米那普明（n = 1）ROR = 0.4（95%CI[0.1 - 2.9]）与嗜睡无关。
在测试的30种抗抑郁药中，与原假设一致，阿莫沙平具有最强的5-HT2C受体结合亲和力，且嗜睡报告几率最高。托莫西汀在总体嗜睡报告几率中排名第二，在这30种化合物中与NET的结合亲和力最强。米氮平，一种四环类抗抑郁药，在嗜睡报告几率中排名第11位，且具有最强的H1受体结合亲和力。本研究提供了30种具有广泛临床适应症的抗抑郁化合物中嗜睡情况的信息性排名，同时也为精神药理学中潜在的药物重新利用提供了见解。
