PMC:4235387 / 12725-18394 JSONTXT

{"project":"NEUROSES","denotations":[{"id":"T324","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T325","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T326","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T261","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T262","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T263","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T264","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T265","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T266","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T267","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T268","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T269","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T270","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T271","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T272","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T273","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T274","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T275","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T276","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T277","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T278","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T279","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T280","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T281","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T282","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T283","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T284","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T285","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T286","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T287","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T288","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T289","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T290","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T291","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T292","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T293","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T294","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T295","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T296","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T297","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T298","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T299","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T300","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T301","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T302","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T303","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T304","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T305","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T306","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T307","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T308","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T309","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T310","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T311","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T312","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T313","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T314","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T315","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T316","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T317","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T318","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T319","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T320","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T321","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T322","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T323","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T327","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T328","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T329","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T330","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T331","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T332","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T333","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T334","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T335","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T336","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T337","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T338","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T339","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T340","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T341","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T342","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T343","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T344","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T345","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T346","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T347","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T348","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T349","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T350","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T351","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T352","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T353","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T354","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T355","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T356","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T357","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T358","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T359","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T360","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T361","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T362","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T363","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T364","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T365","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T366","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T367","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T368","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T369","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T370","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T371","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T372","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T373","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T374","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T375","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T376","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T377","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T378","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T379","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T380","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T381","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T382","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T383","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T384","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T385","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T386","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T387","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T388","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T389","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T390","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T391","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T392","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T393","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T394","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T395","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T396","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T397","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T398","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T399","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T400","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T401","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T402","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T403","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T404","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T405","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T406","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T407","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T408","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T409","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T410","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T411","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T412","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T413","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T414","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T415","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T416","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T417","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T418","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T419","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T420","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T421","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T422","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T423","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T424","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T425","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T426","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T427","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T428","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T429","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T430","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T431","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T432","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T433","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T434","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T435","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T436","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T437","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T438","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T439","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T440","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T441","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T442","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T443","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T444","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T445","span":{"begin":1643,"end":1646},"obj":"PATO_0000308"},{"id":"T446","span":{"begin":1659,"end":1663},"obj":"PATO_0000125"},{"id":"T447","span":{"begin":1714,"end":1724},"obj":"CHEBI_36796"},{"id":"T448","span":{"begin":2676,"end":2686},"obj":"CHEBI_36796"},{"id":"T449","span":{"begin":1749,"end":1754},"obj":"PATO_0001177"},{"id":"T450","span":{"begin":2034,"end":2039},"obj":"PATO_0001177"},{"id":"T451","span":{"begin":1755,"end":1760},"obj":"PATO_0000083"},{"id":"T452","span":{"begin":2040,"end":2045},"obj":"PATO_0000083"},{"id":"T453","span":{"begin":1862,"end":1871},"obj":"PATO_0002292"},{"id":"T454","span":{"begin":1931,"end":1934},"obj":"CHEBI_52027"},{"id":"T455","span":{"begin":2077,"end":2089},"obj":"CHEBI_76016"},{"id":"T456","span":{"begin":2122,"end":2134},"obj":"CHEBI_76016"},{"id":"T457","span":{"begin":2767,"end":2779},"obj":"CHEBI_76016"},{"id":"T458","span":{"begin":2940,"end":2952},"obj":"CHEBI_76016"},{"id":"T459","span":{"begin":3206,"end":3217},"obj":"PATO_0001624"},{"id":"T460","span":{"begin":3339,"end":3350},"obj":"PATO_0001624"},{"id":"T461","span":{"begin":3234,"end":3241},"obj":"PATO_0000502"},{"id":"T462","span":{"begin":3380,"end":3386},"obj":"PATO_0000128"},{"id":"T463","span":{"begin":3542,"end":3548},"obj":"PATO_0000128"},{"id":"T464","span":{"begin":3616,"end":3622},"obj":"PATO_0000128"},{"id":"T465","span":{"begin":3821,"end":3827},"obj":"PATO_0000128"},{"id":"T466","span":{"begin":3885,"end":3891},"obj":"PATO_0000128"},{"id":"T467","span":{"begin":3469,"end":3481},"obj":"CHEBI_76016"},{"id":"T468","span":{"begin":3595,"end":3599},"obj":"PATO_0000610"},{"id":"T469","span":{"begin":3600,"end":3605},"obj":"CHEBI_35209"},{"id":"T470","span":{"begin":3828,"end":3837},"obj":"PATO_0000470"},{"id":"T471","span":{"begin":3892,"end":3901},"obj":"PATO_0001997"},{"id":"T472","span":{"begin":3903,"end":3911},"obj":"PATO_0000442"},{"id":"T473","span":{"begin":4059,"end":4066},"obj":"CHEBI_46217"},{"id":"T474","span":{"begin":4059,"end":4066},"obj":"CHEBI_16977"},{"id":"T475","span":{"begin":4059,"end":4066},"obj":"CHEBI_16449"},{"id":"T476","span":{"begin":4088,"end":4097},"obj":"CHEBI_29995"},{"id":"T477","span":{"begin":4088,"end":4097},"obj":"CHEBI_72314"},{"id":"T478","span":{"begin":4165,"end":4171},"obj":"PATO_0000461"},{"id":"T479","span":{"begin":4272,"end":4275},"obj":"CHEBI_52027"},{"id":"T480","span":{"begin":4280,"end":4284},"obj":"CHEBI_25016"},{"id":"T481","span":{"begin":4280,"end":4284},"obj":"CHEBI_27889"},{"id":"T482","span":{"begin":4385,"end":4396},"obj":"CHEBI_16113"},{"id":"T483","span":{"begin":4400,"end":4413},"obj":"CHEBI_17855"},{"id":"T484","span":{"begin":4461,"end":4468},"obj":"PATO_0002123"},{"id":"T485","span":{"begin":4616,"end":4619},"obj":"CHEBI_70255"},{"id":"T486","span":{"begin":4645,"end":4648},"obj":"CHEBI_70255"},{"id":"T487","span":{"begin":4755,"end":4767},"obj":"CHEBI_76016"},{"id":"T488","span":{"begin":4835,"end":4847},"obj":"CHEBI_76016"},{"id":"T489","span":{"begin":5080,"end":5092},"obj":"CHEBI_76016"},{"id":"T490","span":{"begin":5564,"end":5576},"obj":"CHEBI_76016"},{"id":"T491","span":{"begin":991,"end":1001},"obj":"PM3425"},{"id":"T492","span":{"begin":1009,"end":1019},"obj":"PM3425"},{"id":"T493","span":{"begin":1205,"end":1215},"obj":"PM3425"},{"id":"T494","span":{"begin":1392,"end":1402},"obj":"PM3425"},{"id":"T495","span":{"begin":1414,"end":1424},"obj":"PM3425"},{"id":"T496","span":{"begin":991,"end":1001},"obj":"PM3425"},{"id":"T497","span":{"begin":1009,"end":1019},"obj":"PM3425"},{"id":"T498","span":{"begin":1205,"end":1215},"obj":"PM3425"},{"id":"T499","span":{"begin":1392,"end":1402},"obj":"PM3425"},{"id":"T500","span":{"begin":1414,"end":1424},"obj":"PM3425"},{"id":"T250","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T251","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T252","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T253","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T254","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T255","span":{"begin":60,"end":68},"obj":"PATO_0001309"},{"id":"T256","span":{"begin":72,"end":84},"obj":"CHEBI_76016"},{"id":"T257","span":{"begin":943,"end":955},"obj":"CHEBI_76016"},{"id":"T258","span":{"begin":488,"end":492},"obj":"PATO_0001470"},{"id":"T259","span":{"begin":488,"end":492},"obj":"PATO_0000161"},{"id":"T260","span":{"begin":60,"end":68},"obj":"PATO_0001309"}],"text":"Safety\nAmong the 834 evaluable study participants, the mean duration of vortioxetine exposure was 39.5±18.1 (range, 0.1–56.9) weeks. TEAEs were reported by 589 (70.6%) of the 834 study participants, who experienced a total of 2117 events (Table 2). Most TEAEs were mild or moderate in severity. The most frequently reported TEAEs (incidence≥5%) were nausea, headache, nasopharyngitis, diarrhea, dizziness, and upper respiratory tract infection (Table 3). There tended to be a higher TEAE rate in the study participants from the US study compared with the non-US study, with any TEAE reported in 79.3 and 63.2% of the study participants, from the two studies, respectively, although the rates of TEAE-related withdrawal (7.0 vs. 5.1%) and serious TEAEs (4.1 vs. 2.9%) were generally similar between studies. A total of 29 (3.5%) of the study participants experienced 38 serious AEs and five were considered by the investigator to be related to vortioxetine (left hemispheric ischemic stroke, depression, major depression, supraventricular tachycardia, and paroxysmal tachycardia). TEAEs leading to treatment discontinuation occurred in 50 study participants (6.0%), with nausea, somnolence, dizziness, and depression occurring in more than two study participants (Table 2). Three of the study participants with serious related TEAEs withdrew from the study: participants with ischemic stroke, depression, and major depression. The other two study participants, with supraventricular tachycardia and paroxysmal tachycardia, recovered from the events and completed the study as scheduled. The study participant with ischemic stroke was a 78-year-old woman [body mass index (BMI)=33 kg/m2] who had previously received duloxetine 60 mg during the double-blind phase. The study participant had no identifiable risk factors (i.e. hypertension, hyperlipidemia, previous transient ischemic attack, or cardiovascular concerns); however, she did have a previous history of falls that required hospitalization, including a fall during the double-blind phase and a fall after initiation on vortioxetine. The study participant received vortioxetine for a total of 17 days at a daily dose of 5 mg for the initial 7 days and 2.5 mg for 10 days before hospitalization for left hemispheric ischemic stroke. The patient was discharged with right-side weakness and speech deficits. No deaths were reported during the study.\nTable 2 Summary of treatment-emergent adverse events\nTable 3 Treatment-emergent adverse events occurring in at least 5% of the study participants An AE subanalysis during the first 14 days of open-label treatment showed that study participants treated previously with duloxetine (this treatment arm only in the short-term US study), when abruptly switched to vortioxetine as part of this long-term study, experienced a significantly higher rate of dizziness (19.4%) compared with those who had previously received placebo (0.9%) or vortioxetine 2.5 and 5 mg (3.5 and 5.6%, respectively).\nThe incidence of treatment-emergent sexual dysfunction was low, with 18 events among the 834 study participants. Decreased libido was the most commonly reported sexual complaint (n=8; 1%), followed by erectile dysfunction (n=4; 0.5%) and delayed ejaculation (n=2; 0.2%). None of the study participants discontinued the study because of sexual dysfunction-related AEs. With respect to weight, no clinically meaningful differences were observed among the groups administered vortioxetine 2.5, 5, or 10 mg/day. Overall, there was a mean increase in weight of 0.67 kg at the final visit relative to the open-label baseline. Weight changed (increase or decrease) by at least 7% in 155 (18.6%) of 834 study participants (n=105 with an increase≥7% and n=50 with a decrease≥7%). There were 36 study participants (4.3%) with TEAEs of weight increased and 10 study participants (1.2%) with TEAEs of weight decreased. Insomnia was reported in 17 study participants (2.0%).\nSerum chemistry test results showed no clinically meaningful differences among the treatment groups. Alanine aminotransferase and aspartate aminotransferase values of at least three times the upper limit of normal occurred in three (0.4%) and six (0.7%) study participants, respectively; however, these elevations did not lead to discontinuation from the study. No identifiable trend was observed in changes in levels of serum cholesterol or triglycerides. Mean changes from baseline in urinalysis were minimal and not considered clinically meaningful. There were also no clinically meaningful treatment-related trends for vital signs, physical findings, or ECG readings. There were two ECG-related events that were considered serious: one instance of atrial fibrillation (considered unrelated to vortioxetine) and one case of supraventricular tachycardia (possibly related to vortioxetine). One participant had a prolonged Bazett-corrected QT interval; however, this participant had been newly diagnosed with Wolff–Parkinson–White syndrome, and the QT prolongation was not considered by the investigator to be related to vortioxetine. This participant was discontinued from the study.\nOf the 834 study participants included in the analysis, 204 (24.5%) and 74 (8.9%) reported a previous history of suicidal ideation and behavior, respectively (Table 4). During the study, 83 (10%) and three (0.4%) study participants reported suicidal ideation and behavior, respectively. One suicide attempt and two cases of suicidal ideation were reported as serious. None of the three events were considered related to vortioxetine; all study participants recovered.\nTable 4 Suicide-related events on the basis of C-SSRS\n\nS"}