Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study
Cariprazine, a dopamine D /D and 5-HT receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression. In a double-blind placebo-control...
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| Veröffentlicht in: | The American journal of psychiatry 2019-06, Vol.176 (6), p.439-448 |
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| creator | Earley, Willie Burgess, Maria Victoria Rekeda, Ludmyla Dickinson, Regan Szatmári, Balázs Németh, György McIntyre, Roger S Sachs, Gary S Yatham, Lakshmi N |
| description | Cariprazine, a dopamine D
/D
and 5-HT
receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression.
In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity.
Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 [95% CI=-0.5, 0.0] for the 1.5 mg/day group and -0.3 [95% CI=-0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups.
Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression. |
| doi_str_mv | 10.1176/appi.ajp.2018.18070824 |
| format | Article |
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/D
and 5-HT
receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression.
In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity.
Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 [95% CI=-0.5, 0.0] for the 1.5 mg/day group and -0.3 [95% CI=-0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups.
Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression.</description><identifier>ISSN: 0002-953X</identifier><identifier>EISSN: 1535-7228</identifier><identifier>DOI: 10.1176/appi.ajp.2018.18070824</identifier><identifier>PMID: 30845817</identifier><language>eng</language><publisher>United States: American Psychiatric Association</publisher><subject>Adult ; Antipsychotic Agents - therapeutic use ; Bipolar disorder ; Bipolar Disorder - drug therapy ; Bipolar Disorder - psychology ; Depression - drug therapy ; Depression - psychology ; Dopamine ; Double-Blind Method ; Double-blind studies ; Female ; Humans ; Male ; Mental depression ; Middle Aged ; Piperazines - therapeutic use ; Placebo effect ; Receptor, Serotonin, 5-HT1A ; Receptors, Dopamine D2 - agonists ; Receptors, Dopamine D3 - agonists ; Serotonin 5-HT1 Receptor Agonists - therapeutic use ; Treatment Outcome</subject><ispartof>The American journal of psychiatry, 2019-06, Vol.176 (6), p.439-448</ispartof><rights>Copyright American Psychiatric Association Jun 1, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-9447ab281a3f8ccb5e02e6d5d3ccbc3494f55b0ab69b1a70c089cfa32ae280dd3</citedby><cites>FETCH-LOGICAL-c387t-9447ab281a3f8ccb5e02e6d5d3ccbc3494f55b0ab69b1a70c089cfa32ae280dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2855,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30845817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Earley, Willie</creatorcontrib><creatorcontrib>Burgess, Maria Victoria</creatorcontrib><creatorcontrib>Rekeda, Ludmyla</creatorcontrib><creatorcontrib>Dickinson, Regan</creatorcontrib><creatorcontrib>Szatmári, Balázs</creatorcontrib><creatorcontrib>Németh, György</creatorcontrib><creatorcontrib>McIntyre, Roger S</creatorcontrib><creatorcontrib>Sachs, Gary S</creatorcontrib><creatorcontrib>Yatham, Lakshmi N</creatorcontrib><title>Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study</title><title>The American journal of psychiatry</title><addtitle>Am J Psychiatry</addtitle><description>Cariprazine, a dopamine D
/D
and 5-HT
receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression.
In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity.
Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 [95% CI=-0.5, 0.0] for the 1.5 mg/day group and -0.3 [95% CI=-0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups.
Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression.</description><subject>Adult</subject><subject>Antipsychotic Agents - therapeutic use</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - drug therapy</subject><subject>Bipolar Disorder - psychology</subject><subject>Depression - drug therapy</subject><subject>Depression - psychology</subject><subject>Dopamine</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Mental depression</subject><subject>Middle Aged</subject><subject>Piperazines - therapeutic use</subject><subject>Placebo effect</subject><subject>Receptor, Serotonin, 5-HT1A</subject><subject>Receptors, Dopamine D2 - agonists</subject><subject>Receptors, Dopamine D3 - agonists</subject><subject>Serotonin 5-HT1 Receptor Agonists - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0002-953X</issn><issn>1535-7228</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtP3TAQha2KqtxC_wKyxIZNbv2IE6c7uEBbCamogMTOmtiT1ldOHOxkAb-eXPFYsBodzTlHo_kIOeJszXldfYdx9GvYjmvBuF5zzWqmRfmJrLiSqqiF0HtkxRgTRaPk_T75mvN2kUzW4gvZl0yXSvN6Rf5tIPkxwZMfkN4mhKnHYaKxo2d-jAESPccxYc4-Dj_oKf0Lg4u9f0JHz-PcBizOgh8cvQ5gsY3FJg5TiiEs--v_kJFKejPN7vGQfO4gZPz2Og_I3eXF7eZXcfXn5-_N6VVhpa6noinLGlqhOchOW9sqZAIrp5xchJVlU3ZKtQzaqmk51Mwy3dgOpAAUmjknD8jJS--Y4sOMeTK9zxZDgAHjnI3gulEVZ0os1uMP1m2c07BcZ4QoGZdaabm4qheXTTHnhJ0Zk-8hPRrOzA6F2aEwCwqzQ2HeUCzBo9f6ue3Rvcfefi-fAXlMhwA</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Earley, Willie</creator><creator>Burgess, Maria Victoria</creator><creator>Rekeda, Ludmyla</creator><creator>Dickinson, Regan</creator><creator>Szatmári, Balázs</creator><creator>Németh, György</creator><creator>McIntyre, Roger S</creator><creator>Sachs, Gary S</creator><creator>Yatham, Lakshmi N</creator><general>American Psychiatric Association</general><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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20190601</creationdate><title>Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study</title><author>Earley, Willie ; Burgess, Maria Victoria ; Rekeda, Ludmyla ; Dickinson, Regan ; Szatmári, Balázs ; Németh, György ; McIntyre, Roger S ; Sachs, Gary S ; Yatham, Lakshmi N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-9447ab281a3f8ccb5e02e6d5d3ccbc3494f55b0ab69b1a70c089cfa32ae280dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Antipsychotic Agents - therapeutic use</topic><topic>Bipolar disorder</topic><topic>Bipolar Disorder - drug therapy</topic><topic>Bipolar Disorder - psychology</topic><topic>Depression - drug therapy</topic><topic>Depression - psychology</topic><topic>Dopamine</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Mental depression</topic><topic>Middle Aged</topic><topic>Piperazines - therapeutic use</topic><topic>Placebo effect</topic><topic>Receptor, Serotonin, 5-HT1A</topic><topic>Receptors, Dopamine D2 - agonists</topic><topic>Receptors, Dopamine D3 - agonists</topic><topic>Serotonin 5-HT1 Receptor Agonists - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Earley, Willie</creatorcontrib><creatorcontrib>Burgess, Maria Victoria</creatorcontrib><creatorcontrib>Rekeda, Ludmyla</creatorcontrib><creatorcontrib>Dickinson, Regan</creatorcontrib><creatorcontrib>Szatmári, Balázs</creatorcontrib><creatorcontrib>Németh, György</creatorcontrib><creatorcontrib>McIntyre, Roger S</creatorcontrib><creatorcontrib>Sachs, Gary S</creatorcontrib><creatorcontrib>Yatham, Lakshmi N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Earley, Willie</au><au>Burgess, Maria Victoria</au><au>Rekeda, Ludmyla</au><au>Dickinson, Regan</au><au>Szatmári, Balázs</au><au>Németh, György</au><au>McIntyre, Roger S</au><au>Sachs, Gary S</au><au>Yatham, Lakshmi N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study</atitle><jtitle>The American journal of psychiatry</jtitle><addtitle>Am J Psychiatry</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>176</volume><issue>6</issue><spage>439</spage><epage>448</epage><pages>439-448</pages><issn>0002-953X</issn><eissn>1535-7228</eissn><abstract>Cariprazine, a dopamine D
/D
and 5-HT
receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression.
In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity.
Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 [95% CI=-0.5, 0.0] for the 1.5 mg/day group and -0.3 [95% CI=-0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups.
Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression.</abstract><cop>United States</cop><pub>American Psychiatric Association</pub><pmid>30845817</pmid><doi>10.1176/appi.ajp.2018.18070824</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Psychiatric Publishing Journals (1997-Present); Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Antipsychotic Agents - therapeutic use Bipolar disorder Bipolar Disorder - drug therapy Bipolar Disorder - psychology Depression - drug therapy Depression - psychology Dopamine Double-Blind Method Double-blind studies Female Humans Male Mental depression Middle Aged Piperazines - therapeutic use Placebo effect Receptor, Serotonin, 5-HT1A Receptors, Dopamine D2 - agonists Receptors, Dopamine D3 - agonists Serotonin 5-HT1 Receptor Agonists - therapeutic use Treatment Outcome |
| title | Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study |
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