{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:12:35Z","timestamp":1789726355291,"version":"4.0.1"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91639203"],"award-info":[{"award-number":["91639203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070435"],"award-info":[{"award-number":["82070435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Clinical Hypertension"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In a randomized, double\u2010blind, placebo\u2010controlled trial, we investigated antihypertensive treatment effect of a quadruple single\u2010pill combination of reserpine 0.1\u00a0mg, dihydralazine 12.5\u00a0mg, hydrochlorothiazide 12.5\u00a0mg, and triamterene 12.5\u00a0mg, and changes in plasma levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in patients with grade 1 hypertension. Eligible patients with a systolic\/diastolic blood pressure (BP, average of six readings at two clinic visits during a 4\u2010week run\u2010in period) of 140\u2010159\/90\u201399\u00a0mmHg were randomly assigned to the quadruple combination (<jats:italic>n<\/jats:italic>\u00a0=\u00a030) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a030). The randomized patients were instructed to take a pill of the combination or placebo once daily and followed up at 4, 8, and 12\u00a0weeks, respectively. Monoamine neurotransmitters were measured at baseline and 12\u00a0weeks of follow\u2010up. After 12\u2010week treatment, systolic\/diastolic BP significantly (<jats:italic>p<\/jats:italic>\u00a0\u2264\u00a0.0001) decreased from 140.8\u00a0\u00b1\u00a07.9\/89.5\u00a0\u00b1\u00a07.5\u00a0mmHg at baseline by 9.8\u00a0\u00b1\u00a01.8\/6.4\u00a0\u00b1\u00a01.3\u00a0mmHg in the combination group. The corresponding values in the placebo group were 141.3\u00a0\u00b1\u00a07.9\/90.3\u00a0\u00b1\u00a07.3\u00a0mmHg and 5.2\u00a0\u00b1\u00a01.8\/0.4\u00a0\u00b1\u00a01.3\u00a0mmHg, respectively. The between\u2010group differences in systolic\/diastolic BP changes were \u22124.6\/\u22126.0\u00a0mmHg (95% CI, \u22129.7 to 0.6\/\u22129.7 to \u22122.2\u00a0mmHg, <jats:italic>p<\/jats:italic>\u00a0\u2264\u00a0.08). The control rate of hypertension was higher in the combination than placebo group (63.3% vs. 16.7%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0002). Plasma serotonin, but not norepinephrine or dopamine, changed in both treatment and placebo groups (<jats:italic>p<\/jats:italic>\u00a0\u2264\u00a0.01). Nonetheless, plasma norepinephrine tended to decrease in the treatment group (\u221234.4\u00a0pg\/ml, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.09). Adverse events occurred in 5 (16.7%) and 3 (10.0%) patients in the combination and placebo groups, respectively. Our study showed that the quadruple combination reduced BP and caused some changes in plasma neurotransmitters.<\/jats:p>","DOI":"10.1111\/jch.14207","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T18:51:19Z","timestamp":1612810279000},"page":"815-822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A double\u2010blind, placebo\u2010controlled trial on the antihypertensive treatment effect of a quadruple single\u2010pill combination"],"prefix":"10.1111","volume":"23","author":[{"given":"Lei\u2010Xiao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical Trials Shanghai Key Laboratory of Hypertension The Shanghai Institute of Hypertension Department of Hypertension Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical Trials Shanghai Key Laboratory of Hypertension The Shanghai Institute of Hypertension Department of Hypertension Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hypertension Zhoukou Central Hospital Zhoukou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hypertension Zhoukou Central Hospital Zhoukou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Sheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Zhejiang Provincial People\u2019s Hospital Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Zhejiang Provincial People\u2019s Hospital Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-6991","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hypertension Ruijin Hospital North Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Li","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Hypertension Ruijin Hospital North Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-1524","authenticated-orcid":false,"given":"Ji\u2010Guang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical Trials Shanghai Key Laboratory of Hypertension The Shanghai Institute of Hypertension Department of Hypertension Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,6]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"182","article-title":"Chinese guidelines for prevention and treatment of hypertension\u2010a report of the revision committee of Chinese guidelines for prevention and treatment of hypertension","volume":"16","author":"Joint Committee for Guideline Revision","year":"2019","journal-title":"J Geriatr Cardiol"},{"key":"e_1_2_9_3_1","first-page":"e13","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"71","author":"Whelton PK","year":"2018","journal-title":"Hypertension"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001940"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006040368"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256917"},{"key":"e_1_2_9_8_1","first-page":"522","article-title":"Depressive states during Rauwolfia therapy for arterial hypertension; a report of 30 cases","volume":"74","author":"Lemieux G","year":"1956","journal-title":"Can Med Assoc J"},{"key":"e_1_2_9_9_1","first-page":"608","article-title":"No association between low\u2010dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross\u2010sectional study","volume":"16","author":"Zhu GH","year":"2019","journal-title":"J Geriatr Cardiol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145712000843"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2534-08.2008"},{"key":"e_1_2_9_12_1","first-page":"35","article-title":"Effect of serotonin transporter genotype on self\u2010reported efficacy and activity changes of brain prefrontal area in response to placebo","volume":"73","author":"Isawa M","year":"2018","journal-title":"Pharmazie"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092288"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17453674.2018.1543842"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2016.10.009"}],"container-title":["The Journal of Clinical Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jch.14207","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jch.14207","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jch.14207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T05:27:53Z","timestamp":1697088473000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jch.14207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,6]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1111\/jch.14207"],"URL":"https:\/\/doi.org\/10.1111\/jch.14207","archive":["Portico"],"relation":{},"ISSN":["1524-6175","1751-7176"],"issn-type":[{"value":"1524-6175","type":"print"},{"value":"1751-7176","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,6]]},"assertion":[{"value":"2020-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}