Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia
BackgroundPimavanserin prolongs the QT interval, with mean increases in corrected QT (QTc) of 5–8 ms, and is currently being investigated for the treatment of negative symptoms of schizophrenia.ObjectivesTo assess QT interval prolongation in 3 studies investigating once-daily pimavanserin as an adju...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.892199/full |
| _version_ | 1798002276679286784 |
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| author | Dragana Bugarski-Kirola Rene Nunez Ramzey Odetalla I-Yuan Liu Mary Ellen Turner |
| author_facet | Dragana Bugarski-Kirola Rene Nunez Ramzey Odetalla I-Yuan Liu Mary Ellen Turner |
| author_sort | Dragana Bugarski-Kirola |
| collection | DOAJ |
| description | BackgroundPimavanserin prolongs the QT interval, with mean increases in corrected QT (QTc) of 5–8 ms, and is currently being investigated for the treatment of negative symptoms of schizophrenia.ObjectivesTo assess QT interval prolongation in 3 studies investigating once-daily pimavanserin as an adjunct to current antipsychotic treatment in patients with schizophrenia.MethodsElectrocardiograms were unblinded from trials in which pimavanserin or placebo was added to main antipsychotics over 6 weeks (ENHANCE), 26 weeks (ADVANCE), and up to 78 weeks (ongoing 52-week, open-label extension study [study 035]) of treatment. Antipsychotic treatment was permitted throughout these studies. The 3 most frequently used antipsychotic treatments were examined—aripiprazole (including long-acting injectable), risperidone (including long-acting injectable), and olanzapine. QT intervals were corrected (QTc) using Fridericia's method, with elevated risk defined as either postbaseline value maximum of >500 ms or change from baseline to postbaseline maximum of >60 ms.ResultsOf patients treated with adjunctive pimavanserin in ENHANCE, there were no postbaseline QTc values >481 ms; one patient in each of the risperidone and aripiprazole groups had change from baseline to postbaseline maximum >60 ms. More patients had change from baseline to postbaseline maximum ranging from 31 to 60 ms in the risperidone plus adjunctive placebo group (n = 5; 6.6%) than those in the risperidone plus adjunctive pimavanserin group (n = 3, 4.1%). In the pimavanserin plus antipsychotic group of ADVANCE, one patient had postbaseline QTc value >481 ms, and one patient treated with aripiprazole had change from baseline to postbaseline maximum of >60 ms. In study 035, a change from double-blind baseline to overall postbaseline maximum >60 ms occurred in one patient treated with aripiprazole and pimavanserin and in one patient treated with risperidone and pimavanserin. Similar proportions of patients had changes from double-blind baseline to post double-blind baseline maximum between 31 and 60 ms across treatments. No adverse events associated with an increase in the QTc interval were reported.ConclusionsAdjunctive pimavanserin with background antipsychotic treatment showed no evidence of QTc prolongation >500 ms postbaseline, consistent with previously reports on QT prolongation with pimavanserin. |
| first_indexed | 2024-04-11T11:49:32Z |
| format | Article |
| id | doaj.art-34afd38db4714a0ea5843e4cda309bc6 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-04-11T11:49:32Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-34afd38db4714a0ea5843e4cda309bc62022-12-22T04:25:25ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402022-09-011310.3389/fpsyt.2022.892199892199Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophreniaDragana Bugarski-Kirola0Rene Nunez1Ramzey Odetalla2I-Yuan Liu3Mary Ellen Turner4Acadia Pharmaceuticals GmbH, Basel, SwitzerlandAcadia Pharmaceuticals Inc., San Diego, CA, United StatesAcadia Pharmaceuticals Inc., San Diego, CA, United StatesAcadia Pharmaceuticals Inc., San Diego, CA, United StatesAcadia Pharmaceuticals Inc., San Diego, CA, United StatesBackgroundPimavanserin prolongs the QT interval, with mean increases in corrected QT (QTc) of 5–8 ms, and is currently being investigated for the treatment of negative symptoms of schizophrenia.ObjectivesTo assess QT interval prolongation in 3 studies investigating once-daily pimavanserin as an adjunct to current antipsychotic treatment in patients with schizophrenia.MethodsElectrocardiograms were unblinded from trials in which pimavanserin or placebo was added to main antipsychotics over 6 weeks (ENHANCE), 26 weeks (ADVANCE), and up to 78 weeks (ongoing 52-week, open-label extension study [study 035]) of treatment. Antipsychotic treatment was permitted throughout these studies. The 3 most frequently used antipsychotic treatments were examined—aripiprazole (including long-acting injectable), risperidone (including long-acting injectable), and olanzapine. QT intervals were corrected (QTc) using Fridericia's method, with elevated risk defined as either postbaseline value maximum of >500 ms or change from baseline to postbaseline maximum of >60 ms.ResultsOf patients treated with adjunctive pimavanserin in ENHANCE, there were no postbaseline QTc values >481 ms; one patient in each of the risperidone and aripiprazole groups had change from baseline to postbaseline maximum >60 ms. More patients had change from baseline to postbaseline maximum ranging from 31 to 60 ms in the risperidone plus adjunctive placebo group (n = 5; 6.6%) than those in the risperidone plus adjunctive pimavanserin group (n = 3, 4.1%). In the pimavanserin plus antipsychotic group of ADVANCE, one patient had postbaseline QTc value >481 ms, and one patient treated with aripiprazole had change from baseline to postbaseline maximum of >60 ms. In study 035, a change from double-blind baseline to overall postbaseline maximum >60 ms occurred in one patient treated with aripiprazole and pimavanserin and in one patient treated with risperidone and pimavanserin. Similar proportions of patients had changes from double-blind baseline to post double-blind baseline maximum between 31 and 60 ms across treatments. No adverse events associated with an increase in the QTc interval were reported.ConclusionsAdjunctive pimavanserin with background antipsychotic treatment showed no evidence of QTc prolongation >500 ms postbaseline, consistent with previously reports on QT prolongation with pimavanserin.https://www.frontiersin.org/articles/10.3389/fpsyt.2022.892199/fullpimavanserinschizophreniaQT intervalantipsychoticsadjunctive therapy |
| spellingShingle | Dragana Bugarski-Kirola Rene Nunez Ramzey Odetalla I-Yuan Liu Mary Ellen Turner Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia Frontiers in Psychiatry pimavanserin schizophrenia QT interval antipsychotics adjunctive therapy |
| title | Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia |
| title_full | Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia |
| title_fullStr | Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia |
| title_full_unstemmed | Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia |
| title_short | Effects of adjunctive pimavanserin and current antipsychotic treatment on QT interval prolongation in patients with schizophrenia |
| title_sort | effects of adjunctive pimavanserin and current antipsychotic treatment on qt interval prolongation in patients with schizophrenia |
| topic | pimavanserin schizophrenia QT interval antipsychotics adjunctive therapy |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.892199/full |
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