A case of adolescent lactation due to the drug blonanserin

A case of adolescent lactation due to the drug blonanserin | 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 A case of adolescent lactation due to the drug blonanserin Peiyuan Tang, Chongze Wang, Wu Hong, Zhenghui Yi, Qinyu Lv This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4718045/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Oct, 2024 Read the published version in BMC Psychiatry → Version 1 posted 10 You are reading this latest preprint version Abstract Background Second-generation antipsychotic drugs are increasingly used to treat depressive disorders with psychotic symptoms. In addition to effectively managing psychotic symptoms, second-generation antipsychotics can also result in adverse drug reactions in patients., which should not be underestimated. Case presentation We report the case of 14 years old unmarried female patient with depression. At first, she started with moping and gradually developed into self-injury and whispering. After antidepressant treatment combined with the second-generation antipsychotic drug blonanserin, the patient's psychotic and depressive symptoms improved significantly, while the patient developed lactation, which stopped after the medication was changed. Conclusions Although Blonanserin's clinical trials have reported rare adverse reactions like elevated prolactin levels and even lactation, caution is still needed in clinical application of the drug. This case is expected to improve psychiatrists' choice of antidepressant therapy in combination with antipsychotic drugs. Blonanserin Depressive disorders with psychotic symptoms Background Blonanserin is a second-generation antipsychotic drug, a D2/5-HT2 receptor blocker developed by Sumitomo Pharmaceutical Co., Ltd., in Japan that can antagonize 5-HT2A receptors, thus reducing the occurrence of EPS [ 1 ] . Blonanserin can relieve negative symptoms, positive symptoms, and cognitive deficits in patients [ 1 ] . The current treatments for depressive episodes with psychotic symptoms are mostly antidepressants combined with second-generation antipsychotics. Combined with the current young age at which depressive episodes occur and the adverse effects of medications, the selection of second-generation antipsychotics for use in children and adolescents should be approached with caution. Current FDA-approved medications include aripiprazole and risperidone; however, risperidone is highly susceptible to hyperprolactinemia. A 52-week, multicenter, open-label extension study showed that blonanserin was effective in controlling and reducing psychotic symptoms in adolescents with schizophrenia while producing mild adverse effects [ 2 ] . Blonanserin is recommended for adolescent schizophrenia patients in Japan and is also associated with fewer adverse effects. This article describes the case of an adolescent with depressive disorders and psychotic symptoms who developed lactation after antidepressant treatment combined with blonanserin. Case presentation A 14-year-old unmarried female patient was hospitalized for sullenness and self-injury accompanied by whispering. Psychiatric examination revealed depressed mood, command and comment hallucinations, persecutory delusions, delusions of physical influence, and a diagnosis of major depressive disorder with psychotic symptoms according to the International Classification of Diseases-10 (ICD-10). The patient's blood and biochemical tests and cranial magnetic resonance imaging results were unremarkable. Fluvoxamine was given as an antidepressant, lithium carbonate was used for mood stabilization and prevention of suicidal behavior, and blonanserin was used to control the patient's psychiatric symptoms. The dosage of blonanserin was increased from 4 mg/day to a therapeutic dosage of 12 mg/day. After 17 days of treatment, lactation occurred (enlarged breasts with increased milk production), and the patient's lactogen concentration increased from 444.30 mIU/L (20.96 ng/ml) to 1,803.00 mIU/L (85.05 ng/ml). Blonanserin was withdrawn and replaced with aripiprazole at 2.5 mg/day, which was gradually increased to 5 mg/day. The original fluvoxamine and lithium carbonate doses were maintained. The patient's lactation stopped four days after treatment with aripiprazole, and the lactogen concentration was 52.68 mIU/L (2.48 ng/ml) at the time of discharge (Table 1 ). Other medications were continued without dose adjustment. The patient was discharged from the hospital and followed up regularly with no obvious depression, hallucinations, or delusions and did not have lactate, with no complaints of physical discomfort. Table 1 Changes in prolactin. Date Prolactin values(mIU/L) Notice March 6 444.3 Baseline March 23 1803.0 Presence of lactation March 27 213.0 Lactation Cessation April 3 52.68 Discharge Discussion and conclusion Here, we report a depressed adolescent female with psychotic symptoms who developed lactation after treatment with blonanserin and lactation management. Blonanserin causes elevated prolactin via the same mechanism as most antipsychotics; both agents reduce the inhibition of prolactin secretion release by antagonizing the D₂ receptor in the nodal funnel pathway, which in turn causes increased prolactin [ 1 ] . However, D₂ receptor blockade in the nodal funnel pathway is different because of the presence of the blood‒brain barrier. The B/P (brain/pituitary) ratio of antipsychotics is proposed to reflect the difficulty of entering the brain through the blood–brain barrier; the higher the B/P ratio is, the easier it is for the drug to enter the brain, and the lower the B/P ratio is, the more difficult it is for the drug to enter the brain through the blood–brain barrier. D2 receptor blockade in the pituitary is stronger; for example, the B/P ratio of sulpiride was 0.34, that of risperidone was 1.61, that of olanzapine was 2.70 [ 3 ] , and that of blonanserin was 3.88 [ 4 ] . The results indicate that blonanserin exhibits a lesser potential to induce prolactin levels as compared to other antipsychotic medications. Although the pharmacological mechanism indicates that blonanserin increases prolactin levels in patients, this phenomenon has rarely been observed in clinical trials of blonanserin. This is likely due to the antagonistic effect of 5-HT2A receptors, which increase dopaminergic activity [ 5 ] and thus reduce elevated prolactin levels, resulting in a less frequently observed prolactin elevation induced by blonanserin in clinical trials. Short-term hyperprolactinemia causes amenorrhea, decreased libido, and infertility in women and decreased libido and infertility in men, and long-term hyperprolactinemia causes osteoporosis and breast cancer. However, elevated prolactin levels do not necessarily lead to lactation because prolactin, which is synthesized and secreted by the anterior pituitary gland, has a variety of isomeric forms. Among them, the most abundant is monomeric prolactin, which has biological and immunological activities, and less than 10% are tetramers with lower biological activities and polymers of immunoglobulins and monomeric prolactin, called macrolactin [ 6 ] . Because the presence of macroprolactin affects the actual detection of prolactin, the Chinese expert consensus recommends that screening for macroprolactin should be considered in cases of elevated prolactin levels without clinical symptoms or in cases where symptoms do not explain the degree of elevation [ 7 ] . Therefore, screening for macroprolactin is especially needed in cases in which clinical manifestations cannot be matched with laboratory test results. Currently, when antipsychotics that influence prolactin levels are used, baseline prolactin levels must be measured. If the patient's prolactin level is elevated and < 2000 mIU/L (94.34 ng/ml) after starting antipsychotic therapy and if the patient does not have symptoms of hyperprolactinemia, close follow-up observation can be performed. When patients have symptoms of elevated prolactin > 2000 mIU/L (94.34 ng/ml), clinicians need to consider the need to reduce the antipsychotic dose, switch to a prolactin-sparing antipsychotic, combine with aripiprazole, combine with a dopaminergic drug, and refer patients to an endocrinologist. When the prolactin level is > 2000 mIU/L, the patient needs to be excluded from having a pituitary tumor [ 8 ] . Second-generation antipsychotics are increasingly used to treat depression, both as a treatment for depression with psychotic symptoms and as potentiators of antidepressants. Second-generation antipsychotics approved by the Food and FDA for the treatment of schizophrenia in adolescents include aripiprazole, lurasidone, olanzapine, quetiapine, and risperidone. It is particularly important to choose drugs with fewer adverse effects, both in terms of efficacy and improving patient adherence to medication. A randomized, double-blind, placebo-controlled, multicenter study showed that blonanserin was effective in the treatment of acute schizophrenia and had better efficacy for negative symptoms than haloperidol, and blonanserin was well tolerated. The incidence of EPS with 10 mg blonanserin (26.6%) was significantly lower than that with 10 mg haloperidol (53.3%), which resulted in a sustained increase in prolactin levels. However, this phenomenon has not been observed in patients taking blonanserin [ 9 ] . Prospective, multicenter, open-label postmarketing surveillance showed that blonanserin significantly improved psychiatric symptoms in female schizophrenic patients between the ages of 18 and 40 years while being well tolerated and that only 1% of the patients in the surveillance had elevated prolactin levels, and no patients were lactating [ 10 ] . At present, clinical trials of blonanserin have been conducted for schizophrenic patients; serious adverse reactions leading to lactation were not observed in schizophrenic patients, while clinical trials for adolescent schizophrenic patients did not observe such adverse reactions, and a multicenter, double-blind, randomized, placebo-controlled study showed that adolescent schizophrenic patients who were taking blonanserin after their psychiatric symptoms were effectively controlled. Blonanserin is a second-generation antipsychotic approved for use in adolescents in Japan because it is usually associated with mild adverse events [ 11 ] . However, this case suggests that when blonanserin is used, the possibility of developing hyperprolactinemia leading to lactation still needs to be considered. A study revealed that the use of blonanserin transdermal patches was more effective at reducing the occurrence of EPS than the use of oral tablets [ 12 ] , which also suggests that transdermal patches can reduce the increase in prolactin levels compared with the use of tablets; however, these findings need to be verified by additional studies. At the same time, the current clinical trials for blonanserin are all for patients with schizophrenia, and the published results of these studies have not shown that blonanserin causes lactation in patients. There is still a gap in clinical trials for depressed patients with psychotic symptoms, and there is still a need to expand the study population and conduct statistical analyses in the future. This study aims to draw the attention of clinicians to the importance of comprehensive evaluation of adolescent depressed patients before and after antipsychotic use and the management of prolactin. Declarations Acknowledgments The authors would like to thank the patient presented in this case report and her family. Contributors Peiyuan Tang, Chongze Wang, and Qinyu Lv were responsible for clinical care. Peiyuan Tang performed the literature search and drafted the manuscript. Wu Hong, Zhenghui Yi, and Qinyu Lv revised the manuscript, and all the authors contributed to and approved the final manuscript. Funding This work was supported by grants from STI 2030‐Major Projects (grant number: 2022ZD0208500) Competing interest The authors declare that there is no conflict of interest regarding the publication of this article. Ethics approval This study involved human participants, but ethical approval was not required for this study. Consent for publication Written informed consent was obtained from the patient and his legally authorized representative for the publication of this case report in accordance References Murasaki M. Clinical evaluation of blonanserin for schizophrenia: a double-blind trial comparing blonanserin with haloperidol[J]. Jpn J Clin Psychopharmacol, 2007,10:2059Y-2079Y. Saito T, Hyodo Y, Sakaguchi R, et al. Long-Term Safety and Efficacy of Blonanserin Oral Tablet in Adolescents with Schizophrenia: A 52-Week, Multicenter, Open-Label Extension Study[J]. J Child Adolesc Psychopharmacol, 2022,32(1):24-35. Arakawa R, Okumura M, Ito H, et al. Positron emission tomography measurement of dopamine D₂ receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia[J]. J Clin Psychiatry, 2010,71(9):1131-1137. Kishi T, Matsuda Y, Nakamura H, et al. Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials[J]. J Psychiatr Res, 2013,47(2):149-154. Alex K D, Pehek E A. Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission[J]. Pharmacol Ther, 2007,113(2):296-320. McCudden C R, Sharpless J L, Grenache D G. Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin[J]. Clin Chim Acta, 2010,411(3-4):155-160. Chinese Society Of Neuroscience Psychiatry S C R A. Consensus on the management for antipsychotic‑induced hyperprolactinemia (in Chinese) [J]. Chin J Psychiatry, 2021,3(54):163-169. Gupta S, Lakshmanan D A, Khastgir U, et al. Management of antipsychotic-induced hyperprolactinaemia[J]. BJPsych Advances, 2017,23(4):278-286. Garcia E, Robert M, Peris F, et al. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study[J]. CNS Drugs, 2009,23(7):615-625. Bo Q, Wang X, Liu X, et al. Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance[J]. BMC Psychiatry, 2023,23(1):115. Saito T, Sugimoto S, Sakaguchi R, et al. Efficacy and Safety of Blonanserin Oral Tablet in Adolescents with Schizophrenia: A 6-Week, Randomized Placebo-Controlled Study[J]. J Child Adolesc Psychopharmacol, 2022,32(1):12-23. Ohi K, Takai K, Kuramitsu A, et al. Switching from blonanserin oral tablets/powders to transdermal patches alleviates extrapyramidal symptoms in patients with schizophrenia: A 52-week open-label study[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2022,113:110470. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Oct, 2024 Read the published version in BMC Psychiatry → Version 1 posted Editorial decision: Revision requested 10 Sep, 2024 Reviews received at journal 06 Sep, 2024 Reviewers agreed at journal 06 Sep, 2024 Reviews received at journal 04 Sep, 2024 Reviewers agreed at journal 25 Aug, 2024 Reviewers invited by journal 17 Aug, 2024 Editor invited by journal 15 Jul, 2024 Editor assigned by journal 10 Jul, 2024 Submission checks completed at journal 10 Jul, 2024 First submitted to journal 10 Jul, 2024 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. 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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-4718045","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":335741014,"identity":"eaa73366-3f6f-45e4-8871-05b701f8243c","order_by":0,"name":"Peiyuan Tang","email":"","orcid":"","institution":"Shanghai Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"Peiyuan","middleName":"","lastName":"Tang","suffix":""},{"id":335741015,"identity":"56d3fa25-ec07-48e8-838d-46970f3c7371","order_by":1,"name":"Chongze Wang","email":"","orcid":"","institution":"Shanghai Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"Chongze","middleName":"","lastName":"Wang","suffix":""},{"id":335741016,"identity":"9e2738c8-7dae-4835-b0c5-e1e2139f2a02","order_by":2,"name":"Wu Hong","email":"","orcid":"","institution":"Shanghai Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"Wu","middleName":"","lastName":"Hong","suffix":""},{"id":335741017,"identity":"670401c3-270c-46c9-a04f-c2ed528fe5c4","order_by":3,"name":"Zhenghui Yi","email":"","orcid":"","institution":"Shanghai Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"Zhenghui","middleName":"","lastName":"Yi","suffix":""},{"id":335741018,"identity":"a99bc695-89da-47d8-921f-566c9366535d","order_by":4,"name":"Qinyu Lv","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACPiA+gGBUSMjJE9LCBtMCYZyxMDZsIEILgsHYVpEIMQGfFonkjYcL2w4zsLH3GB78OU8igbGB+eGjG3i1pBUcngnSwnPG4DDvNok8dgY2Y+McfFrAKkFaJHIMDjNukyhmbOBhkyZay8GfcyQSGw4Q0sLeg9BygLeBKC1tBYd5zqUDrTsGZByTMDZsJuAXfmbmzZ95yqwZ+NmbN3/8UVMnJ8/e/PAxPi1AYMDAyMZQ3wDnM+NXDtHC8IewqlEwCkbBKBjBAADhSESGUZhkVAAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai Mental Health Center","correspondingAuthor":true,"prefix":"","firstName":"Qinyu","middleName":"","lastName":"Lv","suffix":""}],"badges":[],"createdAt":"2024-07-10 12:33:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4718045/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4718045/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12888-024-06118-y","type":"published","date":"2024-10-18T15:58:09+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67149144,"identity":"34f80765-c89c-479b-a84d-070590a1c063","added_by":"auto","created_at":"2024-10-21 16:12:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":233513,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4718045/v1/d12a2bb5-e7bd-42c1-83ff-a9cdb68c6957.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of adolescent lactation due to the drug blonanserin","fulltext":[{"header":"Background","content":"\u003cp\u003eBlonanserin is a second-generation antipsychotic drug, a D2/5-HT2 receptor blocker developed by Sumitomo Pharmaceutical Co., Ltd., in Japan that can antagonize 5-HT2A receptors, thus reducing the occurrence of EPS\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Blonanserin can relieve negative symptoms, positive symptoms, and cognitive deficits in patients \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The current treatments for depressive episodes with psychotic symptoms are mostly antidepressants combined with second-generation antipsychotics. Combined with the current young age at which depressive episodes occur and the adverse effects of medications, the selection of second-generation antipsychotics for use in children and adolescents should be approached with caution. Current FDA-approved medications include aripiprazole and risperidone; however, risperidone is highly susceptible to hyperprolactinemia. A 52-week, multicenter, open-label extension study showed that blonanserin was effective in controlling and reducing psychotic symptoms in adolescents with schizophrenia while producing mild adverse effects\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Blonanserin is recommended for adolescent schizophrenia patients in Japan and is also associated with fewer adverse effects. This article describes the case of an adolescent with depressive disorders and psychotic symptoms who developed lactation after antidepressant treatment combined with blonanserin.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 14-year-old unmarried female patient was hospitalized for sullenness and self-injury accompanied by whispering. Psychiatric examination revealed depressed mood, command and comment hallucinations, persecutory delusions, delusions of physical influence, and a diagnosis of major depressive disorder with psychotic symptoms according to the International Classification of Diseases-10 (ICD-10). The patient's blood and biochemical tests and cranial magnetic resonance imaging results were unremarkable. Fluvoxamine was given as an antidepressant, lithium carbonate was used for mood stabilization and prevention of suicidal behavior, and blonanserin was used to control the patient's psychiatric symptoms. The dosage of blonanserin was increased from 4 mg/day to a therapeutic dosage of 12 mg/day. After 17 days of treatment, lactation occurred (enlarged breasts with increased milk production), and the patient's lactogen concentration increased from 444.30 mIU/L (20.96 ng/ml) to 1,803.00 mIU/L (85.05 ng/ml). Blonanserin was withdrawn and replaced with aripiprazole at 2.5 mg/day, which was gradually increased to 5 mg/day. The original fluvoxamine and lithium carbonate doses were maintained. The patient's lactation stopped four days after treatment with aripiprazole, and the lactogen concentration was 52.68 mIU/L (2.48 ng/ml) at the time of discharge (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Other medications were continued without dose adjustment. The patient was discharged from the hospital and followed up regularly with no obvious depression, hallucinations, or delusions and did not have lactate, with no complaints of physical discomfort.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in prolactin.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProlactin values(mIU/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNotice\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarch 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e444.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarch 23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1803.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePresence of lactation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarch 27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e213.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLactation Cessation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApril 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDischarge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion and conclusion","content":"\u003cp\u003eHere, we report a depressed adolescent female with psychotic symptoms who developed lactation after treatment with blonanserin and lactation management. Blonanserin causes elevated prolactin via the same mechanism as most antipsychotics; both agents reduce the inhibition of prolactin secretion release by antagonizing the D₂ receptor in the nodal funnel pathway, which in turn causes increased prolactin\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. However, D₂ receptor blockade in the nodal funnel pathway is different because of the presence of the blood‒brain barrier. The B/P (brain/pituitary) ratio of antipsychotics is proposed to reflect the difficulty of entering the brain through the blood\u0026ndash;brain barrier; the higher the B/P ratio is, the easier it is for the drug to enter the brain, and the lower the B/P ratio is, the more difficult it is for the drug to enter the brain through the blood\u0026ndash;brain barrier. D2 receptor blockade in the pituitary is stronger; for example, the B/P ratio of sulpiride was 0.34, that of risperidone was 1.61, that of olanzapine was 2.70\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, and that of blonanserin was 3.88\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The results indicate that blonanserin exhibits a lesser potential to induce prolactin levels as compared to other antipsychotic medications.\u003c/p\u003e \u003cp\u003eAlthough the pharmacological mechanism indicates that blonanserin increases prolactin levels in patients, this phenomenon has rarely been observed in clinical trials of blonanserin. This is likely due to the antagonistic effect of 5-HT2A receptors, which increase dopaminergic activity\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e and thus reduce elevated prolactin levels, resulting in a less frequently observed prolactin elevation induced by blonanserin in clinical trials.\u003c/p\u003e \u003cp\u003eShort-term hyperprolactinemia causes amenorrhea, decreased libido, and infertility in women and decreased libido and infertility in men, and long-term hyperprolactinemia causes osteoporosis and breast cancer. However, elevated prolactin levels do not necessarily lead to lactation because prolactin, which is synthesized and secreted by the anterior pituitary gland, has a variety of isomeric forms. Among them, the most abundant is monomeric prolactin, which has biological and immunological activities, and less than 10% are tetramers with lower biological activities and polymers of immunoglobulins and monomeric prolactin, called macrolactin\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Because the presence of macroprolactin affects the actual detection of prolactin, the Chinese expert consensus recommends that screening for macroprolactin should be considered in cases of elevated prolactin levels without clinical symptoms or in cases where symptoms do not explain the degree of elevation\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Therefore, screening for macroprolactin is especially needed in cases in which clinical manifestations cannot be matched with laboratory test results. Currently, when antipsychotics that influence prolactin levels are used, baseline prolactin levels must be measured. If the patient's prolactin level is elevated and \u0026lt;\u0026thinsp;2000 mIU/L (94.34 ng/ml) after starting antipsychotic therapy and if the patient does not have symptoms of hyperprolactinemia, close follow-up observation can be performed. When patients have symptoms of elevated prolactin\u0026thinsp;\u0026gt;\u0026thinsp;2000 mIU/L (94.34 ng/ml), clinicians need to consider the need to reduce the antipsychotic dose, switch to a prolactin-sparing antipsychotic, combine with aripiprazole, combine with a dopaminergic drug, and refer patients to an endocrinologist. When the prolactin level is \u0026gt;\u0026thinsp;2000 mIU/L, the patient needs to be excluded from having a pituitary tumor\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSecond-generation antipsychotics are increasingly used to treat depression, both as a treatment for depression with psychotic symptoms and as potentiators of antidepressants. Second-generation antipsychotics approved by the Food and FDA for the treatment of schizophrenia in adolescents include aripiprazole, lurasidone, olanzapine, quetiapine, and risperidone. It is particularly important to choose drugs with fewer adverse effects, both in terms of efficacy and improving patient adherence to medication. A randomized, double-blind, placebo-controlled, multicenter study showed that blonanserin was effective in the treatment of acute schizophrenia and had better efficacy for negative symptoms than haloperidol, and blonanserin was well tolerated. The incidence of EPS with 10 mg blonanserin (26.6%) was significantly lower than that with 10 mg haloperidol (53.3%), which resulted in a sustained increase in prolactin levels. However, this phenomenon has not been observed in patients taking blonanserin\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Prospective, multicenter, open-label postmarketing surveillance showed that blonanserin significantly improved psychiatric symptoms in female schizophrenic patients between the ages of 18 and 40 years while being well tolerated and that only 1% of the patients in the surveillance had elevated prolactin levels, and no patients were lactating\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. At present, clinical trials of blonanserin have been conducted for schizophrenic patients; serious adverse reactions leading to lactation were not observed in schizophrenic patients, while clinical trials for adolescent schizophrenic patients did not observe such adverse reactions, and a multicenter, double-blind, randomized, placebo-controlled study showed that adolescent schizophrenic patients who were taking blonanserin after their psychiatric symptoms were effectively controlled. Blonanserin is a second-generation antipsychotic approved for use in adolescents in Japan because it is usually associated with mild adverse events\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, this case suggests that when blonanserin is used, the possibility of developing hyperprolactinemia leading to lactation still needs to be considered.\u003c/p\u003e \u003cp\u003eA study revealed that the use of blonanserin transdermal patches was more effective at reducing the occurrence of EPS than the use of oral tablets\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, which also suggests that transdermal patches can reduce the increase in prolactin levels compared with the use of tablets; however, these findings need to be verified by additional studies. At the same time, the current clinical trials for blonanserin are all for patients with schizophrenia, and the published results of these studies have not shown that blonanserin causes lactation in patients. There is still a gap in clinical trials for depressed patients with psychotic symptoms, and there is still a need to expand the study population and conduct statistical analyses in the future.\u003c/p\u003e \u003cp\u003eThis study aims to draw the attention of clinicians to the importance of comprehensive evaluation of adolescent depressed patients before and after antipsychotic use and the management of prolactin.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the patient presented in this case report and her family.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePeiyuan Tang, Chongze Wang,\u0026nbsp;and\u0026nbsp;Qinyu Lv were responsible for clinical care. Peiyuan Tang\u0026nbsp;performed the\u0026nbsp;literature search and drafted the manuscript. Wu Hong, Zhenghui Yi,\u0026nbsp;and\u0026nbsp;Qinyu Lv revised the manuscript, and all\u0026nbsp;the\u0026nbsp;authors contributed to and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from STI 2030‐Major Projects (grant number: 2022ZD0208500)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest regarding the publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study\u0026nbsp;involved\u0026nbsp;human participants,\u0026nbsp;but ethical approval was\u0026nbsp;not required\u0026nbsp;for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient and his legally authorized representative for the publication of this case report in accordance\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eMurasaki M. Clinical evaluation of blonanserin for schizophrenia: a double-blind trial comparing blonanserin with haloperidol[J]. Jpn J Clin Psychopharmacol, 2007,10:2059Y-2079Y.\u003c/li\u003e\n \u003cli\u003eSaito T, Hyodo Y, Sakaguchi R, et al. Long-Term Safety and Efficacy of Blonanserin Oral Tablet in Adolescents with Schizophrenia: A 52-Week, Multicenter, Open-Label Extension Study[J]. J Child Adolesc Psychopharmacol, 2022,32(1):24-35.\u003c/li\u003e\n \u003cli\u003eArakawa R, Okumura M, Ito H, et al. Positron emission tomography measurement of dopamine D₂ receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia[J]. J Clin Psychiatry, 2010,71(9):1131-1137.\u003c/li\u003e\n \u003cli\u003eKishi T, Matsuda Y, Nakamura H, et al. Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials[J]. J Psychiatr Res, 2013,47(2):149-154.\u003c/li\u003e\n \u003cli\u003eAlex K D, Pehek E A. Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission[J]. Pharmacol Ther, 2007,113(2):296-320.\u003c/li\u003e\n \u003cli\u003eMcCudden C R, Sharpless J L, Grenache D G. Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin[J]. Clin Chim Acta, 2010,411(3-4):155-160.\u003c/li\u003e\n \u003cli\u003eChinese Society Of Neuroscience Psychiatry S C R A. Consensus on the management for antipsychotic‑induced hyperprolactinemia (in Chinese) [J]. Chin J Psychiatry, 2021,3(54):163-169.\u003c/li\u003e\n \u003cli\u003eGupta S, Lakshmanan D A, Khastgir U, et al. Management of antipsychotic-induced hyperprolactinaemia[J]. BJPsych Advances, 2017,23(4):278-286.\u003c/li\u003e\n \u003cli\u003eGarcia E, Robert M, Peris F, et al. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study[J]. CNS Drugs, 2009,23(7):615-625.\u003c/li\u003e\n \u003cli\u003eBo Q, Wang X, Liu X, et al. Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance[J]. BMC Psychiatry, 2023,23(1):115.\u003c/li\u003e\n \u003cli\u003eSaito T, Sugimoto S, Sakaguchi R, et al. Efficacy and Safety of Blonanserin Oral Tablet in Adolescents with Schizophrenia: A 6-Week, Randomized Placebo-Controlled Study[J]. J Child Adolesc Psychopharmacol, 2022,32(1):12-23.\u003c/li\u003e\n \u003cli\u003eOhi K, Takai K, Kuramitsu A, et al. Switching from blonanserin oral tablets/powders to transdermal patches alleviates extrapyramidal symptoms in patients with schizophrenia: A 52-week open-label study[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2022,113:110470.\u003c/li\u003e\n\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":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Blonanserin, Depressive disorders with psychotic symptoms","lastPublishedDoi":"10.21203/rs.3.rs-4718045/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4718045/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e Second-generation antipsychotic drugs are increasingly used to treat depressive disorders with psychotic symptoms. In addition to effectively managing psychotic symptoms, second-generation antipsychotics can also result in adverse drug reactions in patients., which should not be underestimated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e We report the case of 14 years old unmarried female patient with depression. At first, she started with moping and gradually developed into self-injury and whispering. After antidepressant treatment combined with the second-generation antipsychotic drug blonanserin, the patient's psychotic and depressive symptoms improved significantly, while the patient developed lactation, which stopped after the medication was changed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e Although Blonanserin's clinical trials have reported rare adverse reactions like elevated prolactin levels and even lactation, caution is still needed in clinical application of the drug. This case is expected to improve psychiatrists' choice of antidepressant therapy in combination with antipsychotic drugs.\u003c/p\u003e","manuscriptTitle":"A case of adolescent lactation due to the drug blonanserin","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-05 03:31:47","doi":"10.21203/rs.3.rs-4718045/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-10T12:16:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-06T10:31:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"266924130926548803432483325752630562596","date":"2024-09-06T10:24:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-04T22:20:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21387333710887931377936422364919159756","date":"2024-08-26T01:47:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-17T10:58:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-15T14:45:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-11T02:53:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-11T02:52:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2024-07-10T12:31:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cd35e948-113d-427d-883c-63960f978d96","owner":[],"postedDate":"August 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-21T16:05:35+00:00","versionOfRecord":{"articleIdentity":"rs-4718045","link":"https://doi.org/10.1186/s12888-024-06118-y","journal":{"identity":"bmc-psychiatry","isVorOnly":false,"title":"BMC Psychiatry"},"publishedOn":"2024-10-18 15:58:09","publishedOnDateReadable":"October 18th, 2024"},"versionCreatedAt":"2024-08-05 03:31:47","video":"","vorDoi":"10.1186/s12888-024-06118-y","vorDoiUrl":"https://doi.org/10.1186/s12888-024-06118-y","workflowStages":[]},"version":"v1","identity":"rs-4718045","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4718045","identity":"rs-4718045","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}