Acute Psychosis Following Initiation of Ruxolitinib in Post-Polycythaemia Vera Myelofibrosis

Acute Psychosis Following Initiation of Ruxolitinib in Post-Polycythaemia Vera Myelofibrosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Acute Psychosis Following Initiation of Ruxolitinib in Post-Polycythaemia Vera Myelofibrosis Louise Jade Potter, Sachin Shetty, M. Mansour Ceesay This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7291804/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jan, 2026 Read the published version in Annals of Hematology → Version 1 posted 9 You are reading this latest preprint version Abstract Polycythaemia vera (PV) is a myeloproliferative neoplasm (MPN) which can progress to myelofibrosis (MF), a phenomenon termed post-PV MF. Ruxolitinib is a Janus activated kinase (JAK) inhibitor that targets JAK mutations and is approved for treatment of high-risk MF. This is a case report of a patient with Post-PV MF who developed acute psychotic disorder five months after commencing ruxolitinib and whose mental status returned to baseline within one week of stopping ruxolitinib. Importantly, there was no history of mental health disorder and no identifiable triggers for his presentation. Ruxolitinib has not previously been implicated in the development of psychosis. Ruxolitinib is known to modulate immune responses in the central nervous system (CNS) and is thought to reduce microglia activation, thus reducing neuroinflammation. Such neuromodulation in the CNS may pose a potential mechanism by which ruxolitinib can affect mental status, however these signalling pathways are not clearly defined and future work into this theory is required. Ruxolitinib Polycythaemia Vera Myelofibrosis Psychosis Introduction Myeloproliferative neoplasms (MPN) encompass a group of clonal haematological malignancies including chronic myeloid leukaemia, polycythaemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) [ 1 ], which arise from pluripotent haematopoietic stem cells. PV and ET are characterised by progressive hyperproliferation of erythrocytes or thrombocytes, and both can progress to MF, termed post-PV MF and post-ET MF, respectively. MF is characterised by bone marrow fibrosis resulting in progressive splenomegaly and pancytopenia. The World Health Organisation (WHO) grades MF from 0 to 3, with 0 representing healthy bone marrow and 3 indicating significant collagen fibrosis with osteosclerosis [ 2 ]. Janus activated kinase (JAK) 2 genetic mutations, V617F and exon 12, are recognised drivers of MPNs and ruxolitinib, a JAK inhibitor, is approved for treatment of high-risk MF. This is a case report of a patient with post-PV MF who developed acute psychosis following treatment with ruxolitinib. Case description A 60-year-old male of black African origin with sickle cell trait presented in 2004 with a haemoglobin of 183 g/l, haematocrit 0.525 L/L, platelets of 602 x10 9 /l with normal white blood counts and neutrophils. He was found to be JAK2 V617F positive with variable allele frequency (VAP) of 30% and undetectable serum erythropoietin of < 2.5 mU/mL. His bone marrow biopsy showed panmyelosis, with prominent erythroid and megakaryocytic proliferation and megakaryocytic clustering diagnostic of Jak2 V617F positive polycythaemia vera. He was treated with venesection and commenced on hydroxycarbamide with good response. After around 7 years, hydroxycarbamide was discontinued due to skin and nail hyperpigmentation. He was switched to anagrelide, and he remained on this with good control of his PV. After approximately 10 years of anagrelide treatment, the patient developed a rising platelet count of 667 x10 9 /l, indicating a loss of therapeutic response, although his spleen size remained normal at 11.7 cm on abdominal ultrasound. A repeat bone marrow biopsy demonstrated hypercellularity (> 90% cellularity) with panmyelosis and WHO grade 3 fibrosis, features consistent with post-PV MF. Our Myeloid gene panel (consisting of 48 genes associated with myeloid malignancies) demonstrated persistence of the JAK2 V617F mutation (VAP 48%) and the presence of two ten-eleven translocation 2 (TET2) mutations, TET2 p.(Cys1193Tyr) (VAP 6%) and TET2 p.(lle830ThrfsTer15) (VAP 18%). Anagrelide was stopped and switched to ruxolitinib. After five months of ruxolitinib treatment the patient presented with insomnia, sudden onset of persecutory delusions and auditory hallucinations. Importantly there was no past or family history of psychiatric illness and aside from unspecific work-related stress, there were no triggers for the onset of psychosis. He did not smoke cigarettes or cannabis nor take any other illicit medications. He was admitted to hospital under section two of the UK Mental Health Act. Investigations including a head CT scan and serology screening for human immunodeficiency virus and syphilis were negative. Autoimmune screening for leucine-rich glioma-inactivated 1, N-methyl-D-aspartate receptor and contactin-associated protein-like 2 antibodies was negative. Therefore, an organic cause for his change in mental status was not detected. He was treated with risperidone but continued to experience florid psychotic symptoms. Ruxolitinib was the only recently started medication and around three weeks into the hospital admission, this was stopped, following haematology advice. Following this his mental status made rapid recovery and one week after the cessation of ruxolitinib he was discharged, following a total of four weeks as an inpatient. Hydroxycarbamide was restarted as an alternative treatment of his post-PV MF. He remains well in the community for over six months and is regularly followed up by the community mental health and the haematology teams. Discussion Ruxolitinib is known to cause haematological adverse effects including anaemia, thrombocytopenia and neutropenia, as well as non-haematological adverse effects such as fatigue, abdominal pain and diarrhoea. In terms of neurological adverse effects, ruxolitinib is frequently reported to cause headache and dizziness. Single case reports document progressive multifocal leukoencephalopathy [ 3 ] and unilateral limb hypoesthesia and weakness [ 4 ]. However, the association of ruxolitinib and acute psychotic disorder has not been previous reported to our knowledge. Clearly, the aetiology of psychosis is multifactorial, yet given the absence of alternative precipitating factors and the temporality of psychotic symptom development following ruxolitinib initiation, this case raises the possibility that ruxolitinib may have caused or precipitated acute psychosis. Ruxolitinib is known to modulate immune responses within the central nervous system (CNS) with studies demonstrating that it attenuates neuroinflammation both in vivo and in vitro through inhibition of the mitogen-activated protein kinase/nuclear factor-κB signalling pathway and reduced microglia and astrocyte activation [ 5 ]. However, how such mechanisms related to acute psychosis remains unclear. Conclusion This is a case report of a patient with post-PV MF who developed acute psychotic disorder five months after commencing ruxolitinib. Importantly there was no history of mental health disorder and no identifiable triggers for his presentation. Ruxolitinib has not previously been implicated in the development of psychosis but is known to cause immunomodulation in the CNS and further work into potential underlying mechanisms warrant studying. Declarations No funds, grants, or other support was received. Written informed consent for publication was obtained from the patient. Ethics declaration: not applicable. Author Contribution L .J.P drafted the main text of the case report with guidance and supervision from M.M.C. S.S contributed to the sections detailing the psychiatric presentation. All authors reviewed and approved the final manuscript. References Tefferi A, Vardiman JW (2008) Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22(1):14–22. https://doi.org/10.1038/sj.leu.2404955 Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. International agency for research on cancer Lyon, France Wathes R, Moule S, Milojkovic D (2013) Progressive Multifocal Leukoencephalopathy Associated with Ruxolitinib. N Engl J Med 369(2):197–198. https://doi.org/10.1056/nejmc1302135 Furia F, Canevini MP, Federici AB, Carraro MC (2020) Unexpected Neurological Symptoms of Ruxolitinib: A Case Report. J Hematol 9(4):137–139. https://doi.org/10.14740/jh642 Min J, Zheng H, Xia H, Tian X, Liang M, Zhang J et al (2024) Ruxolitinib attenuates microglial inflammatory response by inhibiting NF-κB/MAPK signaling pathway. Eur J Pharmacol 968:176403. https://doi.org/10.1016/j.ejphar.2024.176403 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Jan, 2026 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 02 Nov, 2025 Reviews received at journal 27 Oct, 2025 Reviews received at journal 15 Sep, 2025 Reviewers agreed at journal 11 Sep, 2025 Reviewers agreed at journal 09 Sep, 2025 Reviewers invited by journal 06 Aug, 2025 Editor assigned by journal 06 Aug, 2025 Submission checks completed at journal 06 Aug, 2025 First submitted to journal 04 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7291804","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":496784584,"identity":"de874f44-fa67-4bb4-92ce-fc245fc7af7a","order_by":0,"name":"Louise Jade Potter","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIie3Pv0vDQBTA8ZflspzJGif/hRcCESHqv3IlcFPwx5ahQ6BQl6pr+18EBOcLh5fldM5mwNWh3eJSTdo6KAl1dLgvvDfdB+4BmEz/MKcdAUA2e5PbrRoAhwj5QQQDOMzAytgesu2boNhH7JlfNKlz5JS3xduqiS6DcnZcszQKwJZPeR+hGiXVxF/olxgF4yePWvsZ0zwEynnVR7wEpTUlVl4loSeYxLBK/Gw0lRF4NBwixceanOev7x35xGD+ByIOMjLKK9oRgehtSThIqLqSVJF4oS9i1DxGT6vreXtLQAZuce3Jw6oZq9O78rmo0+gM3ZtJvlymkX9vS9VHdql26O8PDD/vGvcQk8lkMu36ArJlbBjOV8S8AAAAAElFTkSuQmCC","orcid":"","institution":"King's College Hospital NHS Foundation Trust","correspondingAuthor":true,"prefix":"","firstName":"Louise","middleName":"Jade","lastName":"Potter","suffix":""},{"id":496784585,"identity":"cfc6df9a-fb58-41f6-b849-15899830aaa7","order_by":1,"name":"Sachin Shetty","email":"","orcid":"","institution":"Kent and Medway NHS and Social Care Partnership Trust","correspondingAuthor":false,"prefix":"","firstName":"Sachin","middleName":"","lastName":"Shetty","suffix":""},{"id":496784586,"identity":"6263b7aa-256e-4e49-bd1b-d745030abf3d","order_by":2,"name":"M. Mansour Ceesay","email":"","orcid":"","institution":"King's College Hospital NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"Mansour","lastName":"Ceesay","suffix":""}],"badges":[],"createdAt":"2025-08-04 13:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7291804/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7291804/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-026-06764-0","type":"published","date":"2026-01-23T15:59:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":101152187,"identity":"1e1e9359-4b72-49d5-b970-4cce98c35296","added_by":"auto","created_at":"2026-01-26 16:10:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":227520,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7291804/v1/5831e8bb-1db2-4ac2-8fcf-71589c790af8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute Psychosis Following Initiation of Ruxolitinib in Post-Polycythaemia Vera Myelofibrosis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMyeloproliferative neoplasms (MPN) encompass a group of clonal haematological malignancies including chronic myeloid leukaemia, polycythaemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], which arise from pluripotent haematopoietic stem cells. PV and ET are characterised by progressive hyperproliferation of erythrocytes or thrombocytes, and both can progress to MF, termed post-PV MF and post-ET MF, respectively. MF is characterised by bone marrow fibrosis resulting in progressive splenomegaly and pancytopenia. The World Health Organisation (WHO) grades MF from 0 to 3, with 0 representing healthy bone marrow and 3 indicating significant collagen fibrosis with osteosclerosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Janus activated kinase (JAK) 2 genetic mutations, V617F and exon 12, are recognised drivers of MPNs and ruxolitinib, a JAK inhibitor, is approved for treatment of high-risk MF. This is a case report of a patient with post-PV MF who developed acute psychosis following treatment with ruxolitinib.\u003c/p\u003e"},{"header":"Case description","content":"\u003cp\u003eA 60-year-old male of black African origin with sickle cell trait presented in 2004 with a haemoglobin of 183 g/l, haematocrit 0.525 L/L, platelets of 602 x10\u003csup\u003e9\u003c/sup\u003e/l with normal white blood counts and neutrophils. He was found to be JAK2 V617F positive with variable allele frequency (VAP) of 30% and undetectable serum erythropoietin of \u0026lt;\u0026thinsp;2.5 mU/mL. His bone marrow biopsy showed panmyelosis, with prominent erythroid and megakaryocytic proliferation and megakaryocytic clustering diagnostic of Jak2 V617F positive polycythaemia vera. He was treated with venesection and commenced on hydroxycarbamide with good response. After around 7 years, hydroxycarbamide was discontinued due to skin and nail hyperpigmentation. He was switched to anagrelide, and he remained on this with good control of his PV.\u003c/p\u003e\u003cp\u003eAfter approximately 10 years of anagrelide treatment, the patient developed a rising platelet count of 667 x10\u003csup\u003e9\u003c/sup\u003e/l, indicating a loss of therapeutic response, although his spleen size remained normal at 11.7 cm on abdominal ultrasound. A repeat bone marrow biopsy demonstrated hypercellularity (\u0026gt;\u0026thinsp;90% cellularity) with panmyelosis and WHO grade 3 fibrosis, features consistent with post-PV MF. Our Myeloid gene panel (consisting of 48 genes associated with myeloid malignancies) demonstrated persistence of the JAK2 V617F mutation (VAP 48%) and the presence of two ten-eleven translocation 2 (TET2) mutations, TET2 p.(Cys1193Tyr) (VAP 6%) and TET2 p.(lle830ThrfsTer15) (VAP 18%). Anagrelide was stopped and switched to ruxolitinib.\u003c/p\u003e\u003cp\u003eAfter five months of ruxolitinib treatment the patient presented with insomnia, sudden onset of persecutory delusions and auditory hallucinations. Importantly there was no past or family history of psychiatric illness and aside from unspecific work-related stress, there were no triggers for the onset of psychosis. He did not smoke cigarettes or cannabis nor take any other illicit medications. He was admitted to hospital under section two of the UK Mental Health Act. Investigations including a head CT scan and serology screening for human immunodeficiency virus and syphilis were negative. Autoimmune screening for leucine-rich glioma-inactivated 1, N-methyl-D-aspartate receptor and contactin-associated protein-like 2 antibodies was negative. Therefore, an organic cause for his change in mental status was not detected. He was treated with risperidone but continued to experience florid psychotic symptoms. Ruxolitinib was the only recently started medication and around three weeks into the hospital admission, this was stopped, following haematology advice. Following this his mental status made rapid recovery and one week after the cessation of ruxolitinib he was discharged, following a total of four weeks as an inpatient. Hydroxycarbamide was restarted as an alternative treatment of his post-PV MF. He remains well in the community for over six months and is regularly followed up by the community mental health and the haematology teams.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRuxolitinib is known to cause haematological adverse effects including anaemia, thrombocytopenia and neutropenia, as well as non-haematological adverse effects such as fatigue, abdominal pain and diarrhoea. In terms of neurological adverse effects, ruxolitinib is frequently reported to cause headache and dizziness. Single case reports document progressive multifocal leukoencephalopathy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and unilateral limb hypoesthesia and weakness [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the association of ruxolitinib and acute psychotic disorder has not been previous reported to our knowledge. Clearly, the aetiology of psychosis is multifactorial, yet given the absence of alternative precipitating factors and the temporality of psychotic symptom development following ruxolitinib initiation, this case raises the possibility that ruxolitinib may have caused or precipitated acute psychosis.\u003c/p\u003e\u003cp\u003eRuxolitinib is known to modulate immune responses within the central nervous system (CNS) with studies demonstrating that it attenuates neuroinflammation both \u003cem\u003ein vivo\u003c/em\u003e and \u003cem\u003ein vitro\u003c/em\u003e through inhibition of the mitogen-activated protein kinase/nuclear factor-κB signalling pathway and reduced microglia and astrocyte activation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, how such mechanisms related to acute psychosis remains unclear.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis is a case report of a patient with post-PV MF who developed acute psychotic disorder five months after commencing ruxolitinib. Importantly there was no history of mental health disorder and no identifiable triggers for his presentation. Ruxolitinib has not previously been implicated in the development of psychosis but is known to cause immunomodulation in the CNS and further work into potential underlying mechanisms warrant studying.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eNo funds, grants, or other support was received. Written informed consent for publication was obtained from the patient. Ethics declaration: not applicable.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL .J.P drafted the main text of the case report with guidance and supervision from M.M.C. S.S contributed to the sections detailing the psychiatric presentation. All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTefferi A, Vardiman JW (2008) Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22(1):14\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/sj.leu.2404955\u003c/span\u003e\u003cspan address=\"10.1038/sj.leu.2404955\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSwerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. International agency for research on cancer Lyon, France\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWathes R, Moule S, Milojkovic D (2013) Progressive Multifocal Leukoencephalopathy Associated with Ruxolitinib. N Engl J Med 369(2):197\u0026ndash;198. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/nejmc1302135\u003c/span\u003e\u003cspan address=\"10.1056/nejmc1302135\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFuria F, Canevini MP, Federici AB, Carraro MC (2020) Unexpected Neurological Symptoms of Ruxolitinib: A Case Report. J Hematol 9(4):137\u0026ndash;139. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.14740/jh642\u003c/span\u003e\u003cspan address=\"10.14740/jh642\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMin J, Zheng H, Xia H, Tian X, Liang M, Zhang J et al (2024) Ruxolitinib attenuates microglial inflammatory response by inhibiting NF-κB/MAPK signaling pathway. Eur J Pharmacol 968:176403. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejphar.2024.176403\u003c/span\u003e\u003cspan address=\"10.1016/j.ejphar.2024.176403\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Ruxolitinib, Polycythaemia Vera, Myelofibrosis, Psychosis","lastPublishedDoi":"10.21203/rs.3.rs-7291804/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7291804/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePolycythaemia vera (PV) is a myeloproliferative neoplasm (MPN) which can progress to myelofibrosis (MF), a phenomenon termed post-PV MF. Ruxolitinib is a Janus activated kinase (JAK) inhibitor that targets JAK mutations and is approved for treatment of high-risk MF. This is a case report of a patient with Post-PV MF who developed acute psychotic disorder five months after commencing ruxolitinib and whose mental status returned to baseline within one week of stopping ruxolitinib. Importantly, there was no history of mental health disorder and no identifiable triggers for his presentation. Ruxolitinib has not previously been implicated in the development of psychosis. Ruxolitinib is known to modulate immune responses in the central nervous system (CNS) and is thought to reduce microglia activation, thus reducing neuroinflammation. Such neuromodulation in the CNS may pose a potential mechanism by which ruxolitinib can affect mental status, however these signalling pathways are not clearly defined and future work into this theory is required.\u003c/p\u003e","manuscriptTitle":"Acute Psychosis Following Initiation of Ruxolitinib in Post-Polycythaemia Vera Myelofibrosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-11 16:26:06","doi":"10.21203/rs.3.rs-7291804/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-02T22:07:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-27T15:55:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-15T16:32:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270105264975792518618488631904831270781","date":"2025-09-11T12:30:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"219951634649853895801748248383991982227","date":"2025-09-09T20:45:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-06T19:56:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-06T11:19:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-06T11:19:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-08-04T13:35:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ab5ac532-b21e-4d66-82d2-90186f33c4cf","owner":[],"postedDate":"August 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:07:51+00:00","versionOfRecord":{"articleIdentity":"rs-7291804","link":"https://doi.org/10.1007/s00277-026-06764-0","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2026-01-23 15:59:12","publishedOnDateReadable":"January 23rd, 2026"},"versionCreatedAt":"2025-08-11 16:26:06","video":"","vorDoi":"10.1007/s00277-026-06764-0","vorDoiUrl":"https://doi.org/10.1007/s00277-026-06764-0","workflowStages":[]},"version":"v1","identity":"rs-7291804","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7291804","identity":"rs-7291804","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}