Efficacy of Atomoxetine Versus Midodrine for the Treatment of Orthostatic Hypotension in Autonomic Failure
The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade...
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| Veröffentlicht in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2014-12, Vol.64 (6), p.1235-1240 |
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| container_title | Hypertension (Dallas, Tex. 1979) |
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| creator | Ramirez, Claudia E Okamoto, Luis E Arnold, Amy C Gamboa, Alfredo Diedrich, André Choi, Leena Raj, Satish R Robertson, David Biaggioni, Italo Shibao, Cyndya A |
| description | The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension–related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], −7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, −0.1 to 1.0; P=0.08), improved orthostatic hypotension–related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure. |
| doi_str_mv | 10.1161/HYPERTENSIONAHA.114.04225 |
| format | Article |
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Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension–related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], −7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, −0.1 to 1.0; P=0.08), improved orthostatic hypotension–related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.114.04225</identifier><identifier>PMID: 25185131</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Administration, Oral ; Adrenergic alpha-1 Receptor Agonists - administration & dosage ; Adrenergic Uptake Inhibitors - administration & dosage ; Aged ; Arterial hypertension. Arterial hypotension ; Atomoxetine Hydrochloride ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Pressure - drug effects ; Cardiology. Vascular system ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Hypotension, Orthostatic - drug therapy ; Hypotension, Orthostatic - etiology ; Hypotension, Orthostatic - physiopathology ; Male ; Medical sciences ; Middle Aged ; Midodrine - administration & dosage ; Posture - physiology ; Propylamines - administration & dosage ; Pure Autonomic Failure - complications ; Pure Autonomic Failure - drug therapy ; Pure Autonomic Failure - physiopathology ; Single-Blind Method ; Treatment Outcome</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2014-12, Vol.64 (6), p.1235-1240</ispartof><rights>2014 American Heart Association, Inc</rights><rights>2015 INIST-CNRS</rights><rights>2014 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5775-a3240f780b28ae8c13ee13d86a79fbcf4bf761e676f1a70f02379681fa7b16433</citedby><cites>FETCH-LOGICAL-c5775-a3240f780b28ae8c13ee13d86a79fbcf4bf761e676f1a70f02379681fa7b16433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3685,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28986263$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25185131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramirez, Claudia E</creatorcontrib><creatorcontrib>Okamoto, Luis E</creatorcontrib><creatorcontrib>Arnold, Amy C</creatorcontrib><creatorcontrib>Gamboa, Alfredo</creatorcontrib><creatorcontrib>Diedrich, André</creatorcontrib><creatorcontrib>Choi, Leena</creatorcontrib><creatorcontrib>Raj, Satish R</creatorcontrib><creatorcontrib>Robertson, David</creatorcontrib><creatorcontrib>Biaggioni, Italo</creatorcontrib><creatorcontrib>Shibao, Cyndya A</creatorcontrib><title>Efficacy of Atomoxetine Versus Midodrine for the Treatment of Orthostatic Hypotension in Autonomic Failure</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension–related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], −7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, −0.1 to 1.0; P=0.08), improved orthostatic hypotension–related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.</description><subject>Administration, Oral</subject><subject>Adrenergic alpha-1 Receptor Agonists - administration & dosage</subject><subject>Adrenergic Uptake Inhibitors - administration & dosage</subject><subject>Aged</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Atomoxetine Hydrochloride</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiology. Vascular system</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Cross-Over Studies</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Hypotension, Orthostatic - drug therapy</subject><subject>Hypotension, Orthostatic - etiology</subject><subject>Hypotension, Orthostatic - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Midodrine - administration & dosage</subject><subject>Posture - physiology</subject><subject>Propylamines - administration & dosage</subject><subject>Pure Autonomic Failure - complications</subject><subject>Pure Autonomic Failure - drug therapy</subject><subject>Pure Autonomic Failure - physiopathology</subject><subject>Single-Blind Method</subject><subject>Treatment Outcome</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1v1DAUtBAV3Rb-AjIHjil-jmMnB5CiastWKt0KFgQny_HaxCWJV7ZDu_-eLNsP4MTpSfNm5n0MQq-AnABweLP4djX_uJpffjpfXtaLegLZCWGUFk_QDArKMlbw_CmaEahYVgF8PURHMV4TAowx8Qwd0gLKAnKYoeu5tU4rvcXe4jr53t-a5AaDv5gQx4g_uLVfhx1gfcCpNXgVjEq9GdJOsQyp9TGp5DRebDc-mSE6P2A34HpMfvD91DhTrhuDeY4OrOqieXFXj9Hns_nqdJFdLN-fn9YXmS6EKDKVU0asKElDS2VKDbkxkK9LrkRlG21ZYwUHwwW3oASxhOai4iVYJRrgLM-P0bu972ZserPW06pBdXITXK_CVnrl5N-dwbXyu_8pGc0BBJ0Mqr2BDj7GYOyDFojcBSD_CWACmfwdwKR9-efwB-X9xyfC6zuCilp1NqhBu_jIK6uSU7674u2ed-O7NGXxoxtvTJCtUV1q_2ORX7KTpy0</recordid><startdate>201412</startdate><enddate>201412</enddate><creator>Ramirez, Claudia E</creator><creator>Okamoto, Luis E</creator><creator>Arnold, Amy C</creator><creator>Gamboa, Alfredo</creator><creator>Diedrich, André</creator><creator>Choi, Leena</creator><creator>Raj, Satish R</creator><creator>Robertson, David</creator><creator>Biaggioni, Italo</creator><creator>Shibao, Cyndya A</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>201412</creationdate><title>Efficacy of Atomoxetine Versus Midodrine for the Treatment of Orthostatic Hypotension in Autonomic Failure</title><author>Ramirez, Claudia E ; Okamoto, Luis E ; Arnold, Amy C ; Gamboa, Alfredo ; Diedrich, André ; Choi, Leena ; Raj, Satish R ; Robertson, David ; Biaggioni, Italo ; Shibao, Cyndya A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5775-a3240f780b28ae8c13ee13d86a79fbcf4bf761e676f1a70f02379681fa7b16433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Administration, Oral</topic><topic>Adrenergic alpha-1 Receptor Agonists - administration & dosage</topic><topic>Adrenergic Uptake Inhibitors - administration & dosage</topic><topic>Aged</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Atomoxetine Hydrochloride</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiology. Vascular system</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>Cross-Over Studies</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Hypotension, Orthostatic - drug therapy</topic><topic>Hypotension, Orthostatic - etiology</topic><topic>Hypotension, Orthostatic - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Midodrine - administration & dosage</topic><topic>Posture - physiology</topic><topic>Propylamines - administration & dosage</topic><topic>Pure Autonomic Failure - complications</topic><topic>Pure Autonomic Failure - drug therapy</topic><topic>Pure Autonomic Failure - physiopathology</topic><topic>Single-Blind Method</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramirez, Claudia E</creatorcontrib><creatorcontrib>Okamoto, Luis E</creatorcontrib><creatorcontrib>Arnold, Amy C</creatorcontrib><creatorcontrib>Gamboa, Alfredo</creatorcontrib><creatorcontrib>Diedrich, André</creatorcontrib><creatorcontrib>Choi, Leena</creatorcontrib><creatorcontrib>Raj, Satish R</creatorcontrib><creatorcontrib>Robertson, David</creatorcontrib><creatorcontrib>Biaggioni, Italo</creatorcontrib><creatorcontrib>Shibao, Cyndya A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramirez, Claudia E</au><au>Okamoto, Luis E</au><au>Arnold, Amy C</au><au>Gamboa, Alfredo</au><au>Diedrich, André</au><au>Choi, Leena</au><au>Raj, Satish R</au><au>Robertson, David</au><au>Biaggioni, Italo</au><au>Shibao, Cyndya A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Atomoxetine Versus Midodrine for the Treatment of Orthostatic Hypotension in Autonomic Failure</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2014-12</date><risdate>2014</risdate><volume>64</volume><issue>6</issue><spage>1235</spage><epage>1240</epage><pages>1235-1240</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension–related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], −7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, −0.1 to 1.0; P=0.08), improved orthostatic hypotension–related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>25185131</pmid><doi>10.1161/HYPERTENSIONAHA.114.04225</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0194-911X |
| ispartof | Hypertension (Dallas, Tex. 1979), 2014-12, Vol.64 (6), p.1235-1240 |
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| subjects | Administration, Oral Adrenergic alpha-1 Receptor Agonists - administration & dosage Adrenergic Uptake Inhibitors - administration & dosage Aged Arterial hypertension. Arterial hypotension Atomoxetine Hydrochloride Biological and medical sciences Blood and lymphatic vessels Blood Pressure - drug effects Cardiology. Vascular system Clinical manifestations. Epidemiology. Investigative techniques. Etiology Cross-Over Studies Dose-Response Relationship, Drug Female Follow-Up Studies Humans Hypotension, Orthostatic - drug therapy Hypotension, Orthostatic - etiology Hypotension, Orthostatic - physiopathology Male Medical sciences Middle Aged Midodrine - administration & dosage Posture - physiology Propylamines - administration & dosage Pure Autonomic Failure - complications Pure Autonomic Failure - drug therapy Pure Autonomic Failure - physiopathology Single-Blind Method Treatment Outcome |
| title | Efficacy of Atomoxetine Versus Midodrine for the Treatment of Orthostatic Hypotension in Autonomic Failure |
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