IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials
There is an urgent need for mechanistically novel and more efficacious treatments for schizophrenia, especially those targeting negative and cognitive symptoms with a more favorable side-effect profile. Drug repurposing—the process of identifying new therapeutic uses for already approved compounds—o...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825000581 |
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| author | Jihan K. Zaki Jakub Tomasik Sabine Bahn |
| author_facet | Jihan K. Zaki Jakub Tomasik Sabine Bahn |
| author_sort | Jihan K. Zaki |
| collection | DOAJ |
| description | There is an urgent need for mechanistically novel and more efficacious treatments for schizophrenia, especially those targeting negative and cognitive symptoms with a more favorable side-effect profile. Drug repurposing—the process of identifying new therapeutic uses for already approved compounds—offers a promising approach to overcoming the lengthy, costly, and high-risk process of traditional CNS drug discovery. This review aims to update our previous findings on the clinical drug repurposing pipeline in schizophrenia. We examined studies conducted between 2018 and 2024, identifying 61 trials evaluating 40 unique repurposed drug candidates. These encompassed a broad range of pharmacological mechanisms, including immunomodulation, cognitive enhancement, and hormonal, metabolic, and neurotransmitter modulation. A notable development is the combination of the muscarinic modulators xanomeline, a compound with antipsychotic properties, and trospium, included to mitigate peripheral side effects, now approved by the FDA as the first antipsychotic drug in decades with a fundamentally novel mechanism of action. Moving beyond the traditional dopaminergic paradigm of schizophrenia, such findings highlight opportunities to improve treatment-resistant symptoms and alleviate adverse effects. Overall, the evolving drug repurposing landscape illustrates a significant shift in the rationale for schizophrenia drug development, highlighting the potential of in silico strategies, biomarker-based patient stratification, and personalized treatments that align with underlying pathophysiological processes. |
| format | Article |
| id | doaj-art-24ed2a5b70b440be8b752e3d04246389 |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-24ed2a5b70b440be8b752e3d042463892025-02-02T05:26:50ZengElsevierPharmacological Research1096-11862025-03-01213107633IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trialsJihan K. Zaki0Jakub Tomasik1Sabine Bahn2Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Melville Laboratory for Polymer Synthesis, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UKDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Correspondence to: Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB30AS, UK.Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Correspondence to: Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB30AS, UK.There is an urgent need for mechanistically novel and more efficacious treatments for schizophrenia, especially those targeting negative and cognitive symptoms with a more favorable side-effect profile. Drug repurposing—the process of identifying new therapeutic uses for already approved compounds—offers a promising approach to overcoming the lengthy, costly, and high-risk process of traditional CNS drug discovery. This review aims to update our previous findings on the clinical drug repurposing pipeline in schizophrenia. We examined studies conducted between 2018 and 2024, identifying 61 trials evaluating 40 unique repurposed drug candidates. These encompassed a broad range of pharmacological mechanisms, including immunomodulation, cognitive enhancement, and hormonal, metabolic, and neurotransmitter modulation. A notable development is the combination of the muscarinic modulators xanomeline, a compound with antipsychotic properties, and trospium, included to mitigate peripheral side effects, now approved by the FDA as the first antipsychotic drug in decades with a fundamentally novel mechanism of action. Moving beyond the traditional dopaminergic paradigm of schizophrenia, such findings highlight opportunities to improve treatment-resistant symptoms and alleviate adverse effects. Overall, the evolving drug repurposing landscape illustrates a significant shift in the rationale for schizophrenia drug development, highlighting the potential of in silico strategies, biomarker-based patient stratification, and personalized treatments that align with underlying pathophysiological processes.http://www.sciencedirect.com/science/article/pii/S1043661825000581SchizophreniaDrug repurposingClinical trialBiomarkerPrecision psychiatry |
| spellingShingle | Jihan K. Zaki Jakub Tomasik Sabine Bahn IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials Pharmacological Research Schizophrenia Drug repurposing Clinical trial Biomarker Precision psychiatry |
| title | IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials |
| title_full | IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials |
| title_fullStr | IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials |
| title_full_unstemmed | IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials |
| title_short | IUPHAR review: Drug repurposing in Schizophrenia – An updated review of clinical trials |
| title_sort | iuphar review drug repurposing in schizophrenia an updated review of clinical trials |
| topic | Schizophrenia Drug repurposing Clinical trial Biomarker Precision psychiatry |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825000581 |
| work_keys_str_mv | AT jihankzaki iupharreviewdrugrepurposinginschizophreniaanupdatedreviewofclinicaltrials AT jakubtomasik iupharreviewdrugrepurposinginschizophreniaanupdatedreviewofclinicaltrials AT sabinebahn iupharreviewdrugrepurposinginschizophreniaanupdatedreviewofclinicaltrials |