:Lurasidone

Lurasidone is used to treat schizophrenia and bipolar disorder.{{cite journal | vauthors = Swann AC, Fava M, Tsai J, Mao Y, Pikalov A, Loebel A | title = Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis | journal = CNS Spectrums | volume = 22 | issue = 2 | pages = 228–235 | date = April 2017 | pmid = 28300012 | doi = 10.1017/S1092852917000232 | s2cid = 24653390 | doi-access = free }} In bipolar disorder, it has been studied both as a monotherapy and adjunctive treatment to lithium or valproate.{{cite journal | vauthors = Ali Z, Tegin C, El-Mallakh RS | title = Evaluating lurasidone as a treatment option for bipolar disorder | journal = Expert Opinion on Pharmacotherapy | volume = 21 | issue = 3 | pages = 253–260 | date = February 2020 | pmid = 31957501 | doi = 10.1080/14656566.2019.1695777 | s2cid = 210829608 }}

The European Medicines Agency approved lurasidone for the treatment of schizophrenia for people aged 13 years and older,{{Cite web |url=https://www.ema.europa.eu/en/documents/overview/latuda-epar-medicine-overview_en.pdf |title=Latuda (lurasidone) An overview. European Medicines Agency, 2020 |access-date=6 October 2022 |archive-date=6 October 2022 |archive-url=https://web.archive.org/web/20221006100102/https://www.ema.europa.eu/en/documents/overview/latuda-epar-medicine-overview_en.pdf |url-status=live }} but not for bipolar disorder. In the United States, it is used to treat schizophrenia for people aged 13 years and older, as well as depressive episodes of bipolar disorder age 10 and over as a monotherapy, and in conjunction with lithium or valproate in adults.{{cite book | via = National Center for Biotechnology Information, U.S. National Library of Medicine | chapter = Key Limitations | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK195617/ | title = Lurasidone Hydrochloride (Latuda): Management of Manifestations of Schizophrenia | author = Canadian Agency for Drugs and Technologies in Health | access-date = 30 April 2020 | date = 2014 | publisher = Canadian Agency for Drugs and Technologies in Health | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828152213/https://www.ncbi.nlm.nih.gov/books/NBK195617/ | url-status = live }}

In July 2013, lurasidone received approval for bipolar I depression.{{cite web | vauthors = Lowes R | title = Lurasidone Approved for Bipolar Depression | work = Medscape | date = 2013 | url = http://www.medscape.com/viewarticle/807204 | access-date = 1 October 2013 | archive-date = 2 October 2013 | archive-url = https://web.archive.org/web/20131002013831/http://www.medscape.com/viewarticle/807204 | url-status = live }}{{cite journal | vauthors = Bawa R, Scarff JR | title = Lurasidone: a new treatment option for bipolar depression-a review | journal = Innovations in Clinical Neuroscience | volume = 12 | issue = 1–2 | pages = 21–23 | date = 2015 | pmid = 25852975 | pmc = 4382136 }}

In June 2020, lurasidone was approved in Japan, eight years after its first approval in the United States.{{Cite web |title=Latuda to Finally Hit Japan Market on June 11 |url=https://pj.jiho.jp/article/242267 |access-date=10 October 2022 |website=PHARMA JAPAN |language=en |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010040006/https://pj.jiho.jp/article/242267 |url-status=live }} In Japan it is approved for bipolar depression and schizophrenia.{{Cite web |title=Sumitomo Dainippon Pharma Announces Approval of Atypical Antipsychotic Agent, LATUDA Tablets in Japan | work = IR News {{!}} Investor Relations | publisher = Sumitomo Pharma |url=https://www.sumitomo-pharma.com/ir/news/2020/20200325-1.html |access-date=10 October 2022 |language=en |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010040007/https://www.sumitomo-pharma.com/ir/news/2020/20200325-1.html |url-status=live }}{{Cite web |title=Kusuri-no-Shiori(Drug Information Sheet) Latuda tablets |url=https://www.rad-ar.or.jp/siori/english/search/result?n=43474 |access-date=10 October 2022 |language=en |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010040006/https://www.rad-ar.or.jp/siori/english/search/result?n=43474 |url-status=live }}{{cite journal | vauthors = Okubo R, Hasegawa T, Fukuyama K, Shiroyama T, Okada M | title = Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy | journal = Frontiers in Psychiatry | volume = 12 | pages = 623684 | date = 2021 | pmid = 33679481 | doi = 10.3389/fpsyt.2021.623684 | doi-access = free | pmc = 7930824 }}

Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions being cariprazine,{{cite journal | vauthors = Ragguett RM, McIntyre RS | title = Cariprazine for the treatment of bipolar depression: a review | journal = Expert Review of Neurotherapeutics | volume = 19 | issue = 4 | pages = 317–323 | date = April 2019 | pmid = 30753085 | doi = 10.1080/14737175.2019.1580571 }} quetiapine,{{cite journal | vauthors = Young AH, McElroy SL, Bauer M, Philips N, Chang W, Olausson B, Paulsson B, Brecher M | title = A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I) | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 2 | pages = 150–162 | date = February 2010 | pmid = 20122369 | doi = 10.4088/JCP.08m04995gre | collaboration = EMBOLDEN I (Trial 001) Investigators }}{{cite journal | vauthors = Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D | title = Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression | journal = Journal of Affective Disorders | volume = 121 | issue = 1–2 | pages = 106–115 | date = February 2010 | pmid = 19903574 | doi = 10.1016/j.jad.2009.10.007 | author-link1 = Trisha Suppes }}{{cite journal |doi=10.1111/j.1399-5618.2008.00585.x |title=Corrigendum |year=2008 |journal= Bipolar Disorders |volume=10 |issue=3 |pages= 451|doi-access=free }}{{cite journal | vauthors = Thase ME | title = Quetiapine monotherapy for bipolar depression | journal = Neuropsychiatric Disease and Treatment | volume = 4 | issue = 1 | pages = 11–21 | date = February 2008 | pmid = 18728771 | pmc = 2515925 | doi = 10.2147/ndt.s1162 | doi-access = free }} olanzapine{{cite journal | vauthors = Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C, Mitchell PB, Centorrino F, Risser R, Baker RW, Evans AR, Beymer K, Dube S, Tollefson GD, Breier A | title = Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression | journal = Archives of General Psychiatry | volume = 60 | issue = 11 | pages = 1079–1088 | date = November 2003 | pmid = 14609883 | doi = 10.1001/archpsyc.60.11.1079 | doi-access = free }}{{cite journal | vauthors = Tohen M, Katagiri H, Fujikoshi S, Kanba S | title = Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies | journal = Journal of Affective Disorders | volume = 149 | issue = 1–3 | pages = 196–201 | date = July 2013 | pmid = 23485111 | doi = 10.1016/j.jad.2013.01.022 }}{{cite journal | vauthors = Corya SA, Perlis RH, Keck PE, Lin DY, Case MG, Williamson DJ, Tohen MF | title = A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = 5 | pages = 798–806 | date = May 2006 | pmid = 16841630 | doi = 10.4088/JCP.v67n0514 }} and possibly asenapine{{cite journal | vauthors = Azorin JM, Sapin C, Weiller E | title = Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: results from post hoc analyses | journal = Journal of Affective Disorders | volume = 145 | issue = 1 | pages = 62–69 | date = February 2013 | pmid = 22868059 | doi = 10.1016/j.jad.2012.07.013 }}) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significant antimanic activity,{{cite journal | vauthors = Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR | title = Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis | journal = Lancet | volume = 378 | issue = 9799 | pages = 1306–1315 | date = October 2011 | pmid = 21851976 | doi = 10.1016/S0140-6736(11)60873-8 | s2cid = 25512763 }} which is yet to be clearly demonstrated for lurasidone.

In the early post approval period lurasidone-treated patients with bipolar disorder were retrospectively found to have more complex clinical profiles, comorbidities, and prior treatment history compared to patients initiated with other atypical antipsychotics. The study authors suggest this may be due to "the overall clinical profile of lurasidone, the role perceived for lurasidone in the therapeutic armamentarium by practitioners, and the recent introduction of lurasidone into clinical practice during the study period."{{cite journal | vauthors = Tohen M, Ng-Mak D, Rajagopalan K, Halpern R, Chuang CC, Loebel A | title = Patient Characteristics Associated With Use of Lurasidone Versus Other Atypical Antipsychotics in Patients With Bipolar Disorder: Analysis From a Claims Database in the United States | journal = The Primary Care Companion for CNS Disorders | volume = 19 | issue = 3 | date = June 2017 | pmid = 28590601 | doi = 10.4088/PCC.16m02066 }}

Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.{{Cite web|url=https://medlineplus.gov/druginfo/meds/a611016.html|title=Lurasidone| work = MedlinePlus | publisher = U.S. National Library of Medicine |access-date=11 September 2018|archive-date=23 January 2019|archive-url=https://web.archive.org/web/20190123012938/https://medlineplus.gov/druginfo/meds/a611016.html|url-status=live}}

Lurasidone is contraindicated in individuals who are taking strong inhibitors of the liver enzyme CYP3A4 (ketoconazole, clarithromycin, ritonavir, levodropropizine, etc.) or inducers (carbamazepine, St. John's wort, phenytoin, rifampicin etc.).{{cite journal | vauthors = Chiu YY, Ereshefsky L, Preskorn SH, Poola N, Loebel A | title = Lurasidone drug-drug interaction studies: a comprehensive review | journal = Drug Metabolism and Drug Interactions | volume = 29 | issue = 3 | pages = 191–202 | year = 2014 | pmid = 24825095 | doi = 10.1515/dmdi-2014-0005 | doi-access = free }} The use of lurasidone in pregnant women has not been studied and is not recommended; in animal studies, no risks have been found.Pregnancy category Excretion in breast milk is also unknown; lurasidone is not recommended for breastfeeding women.{{cite journal | title = ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation | journal = Obstetrics and Gynecology | volume = 111 | issue = 4 | pages = 1001–1020 | date = April 2008 | pmid = 18378767 | doi = 10.1097/AOG.0b013e31816fd910 | author1 = ACOG Committee on Practice Bulletins--Obstetrics }} In the United States, it is not indicated for use in children.{{CN|date=May 2025}} The enzyme CYP3A4 is involved in the digestion of drugs. Inhibitors such as grapefruit juice block its function resulting in too much drug in the body.{{Cite web | author = Office of the Commissioner|date=14 July 2021 |title=Grapefruit Juice and Some Drugs Don't Mix |url=https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix |archive-url=https://web.archive.org/web/20190506062425/https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix |url-status=dead |archive-date=6 May 2019 | work = FDA |language=en}}

{{See also|List of adverse effects of lurasidone}}

Side effects are generally similar to other antipsychotics. The drug has a relatively well tolerated side effect profile, with low propensity for QTc interval changes,{{Cite journal | vauthors = Oral H |date=14 September 2018 |title=Lurasidone is not associated with risk of QTc prolongation |url=https://digitalcommons.wayne.edu/crp/vol4/iss2/8 |journal=Clinical Research in Practice: The Journal of Team Hippocrates |volume=4 |issue=2 |doi=10.22237/crp/1536278400 |s2cid=53322344 |issn=2379-4550 |access-date=15 November 2022 |archive-date=15 November 2022 |archive-url=https://web.archive.org/web/20221115033741/https://digitalcommons.wayne.edu/crp/vol4/iss2/8/ |url-status=live }}{{cite journal | vauthors = Javed A, Arthur H, Curtis L, Hansen L, Pappa S | title = Practical Guidance on the Use of Lurasidone for the Treatment of Adults with Schizophrenia | journal = Neurology and Therapy | volume = 8 | issue = 2 | pages = 215–230 | date = December 2019 | pmid = 31098889 | pmc = 6858892 | doi = 10.1007/s40120-019-0138-z }} weight gain and lipid-related adverse effects.{{cite press release |title=Lurasidone Demonstrated Efficacy in Treating Patients With Schizophrenia in Pivotal Phase 3 Study |publisher=Dainippon Sumitomo Pharma |date=26 August 2009 |url=http://www.ds-pharma.com/pdf_view.php?id=170 |access-date=3 October 2016 |archive-date=14 May 2015 |archive-url=https://web.archive.org/web/20150514205205/http://www.ds-pharma.com/pdf_view.php?id=170 |url-status=dead }} In a 2013 meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs, it was found to produce the second least (after haloperidol) weight gain, the least QT interval prolongation, the fourth most extrapyramidal side effects (after haloperidol, zotepine and chlorpromazine), and the sixth least sedation (after paliperidone, sertindole, amisulpride, iloperidone and aripiprazole).{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}

As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for a stroke or transient ischemic attack;{{cite web|url=https://www.drugs.com/latuda.html|publisher=Drugs.com|title=Latuda|access-date=17 December 2010|archive-date=5 April 2019|archive-url=https://web.archive.org/web/20190405041927/https://www.drugs.com/latuda.html|url-status=live}} however, these risks are not likely to be greater than those associated with antipsychotics of other classes.{{cite journal | vauthors = Herrmann N, Mamdani M, Lanctôt KL | title = Atypical antipsychotics and risk of cerebrovascular accidents | journal = The American Journal of Psychiatry | volume = 161 | issue = 6 | pages = 1113–1115 | date = June 2004 | pmid = 15169702 | doi = 10.1176/appi.ajp.161.6.1113 }} Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with antipsychotic use.{{cite web| work = Sunovion Pharmaceuticals|title=Latuda Prescribing Information|url=http://www.latuda.com/LatudaPrescribingInformation.pdf |access-date=25 March 2014|archive-date=12 July 2018|archive-url=https://web.archive.org/web/20180712172540/http://www.latuda.com/LatudaPrescribingInformation.pdf|url-status=live}}

Weight gain is reported in up to 15 and 16 percent of users.{{cite journal | vauthors = Meyer JM, Mao Y, Pikalov A, Cucchiaro J, Loebel A | title = Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia | journal = International Clinical Psychopharmacology | volume = 30 | issue = 6 | pages = 342–350 | date = November 2015 | pmid = 26196189 | pmc = 4593468 | doi = 10.1097/YIC.0000000000000091 }}{{cite journal | vauthors = Ketter TA, Sarma K, Silva R, Kroger H, Cucchiaro J, Loebel A | title = Lurasidone in the Long-Term Treatment of Patients with Bipolar Disorder: A 24-Week Open-Label Extension Study | journal = Depression and Anxiety | volume = 33 | issue = 5 | pages = 424–434 | date = May 2016 | pmid = 26918425 | pmc = 5069590 | doi = 10.1002/da.22479 }} Other possible side effects include vomiting, akathisia, dystonia, parkinsonism, somnolence, dizziness, sedation and nausea.{{cite journal | vauthors = Zheng W, Cai DB, Yang XH, Li L, Zhang QE, Ng CH, Ungvari GS, Li XB, Ning YP, Xiang YT | title = Short-term efficacy and tolerability of lurasidone in the treatment of acute schizophrenia: A meta-analysis of randomized controlled trials | journal = Journal of Psychiatric Research | volume = 103 | pages = 244–251 | date = August 2018 | doi = 10.1016/j.jpsychires.2018.06.005 | pmid = 29906709 | s2cid = 49227958 }}{{cite journal | vauthors = Kolli V, Walia A, Kinnan S | title = Food Matters: Reduction of Lurasidone-Induced Nausea With Meals | journal = The Primary Care Companion for CNS Disorders | volume = 21 | issue = 2 | pages = 18l02343 | date = March 2019 | pmid = 30869204 | doi = 10.4088/PCC.18l02343 | s2cid = 76666344 }}

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.{{cite book | author = BMJ Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}} Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.{{cite book |veditors=Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=978-0-19-852748-0 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |access-date=8 May 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110164012/https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |url-status=live }} Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }} It may also result in reoccurrence of the condition that is being treated.{{cite book |vauthors=Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=978-88-470-2679-7 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |access-date=8 May 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110164029/https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |url-status=live }} Rarely tardive dyskinesia can occur when the medication is stopped.

Blood plasma concentrations may be increased when combined with CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, ritonavir, and voriconazole) possibly leading to more side effects. This has been clinically verified for ketoconazole, which increases lurasidone exposure by a factor of 9, and is also expected for other 3A4 inhibitors such as grapefruit juice. Co-administration of CYP3A4 inducers like rifampicin, carbamazepine or St. John's wort can reduce plasma levels of lurasidone and its active metabolite, and consequently decrease the effects of the drug. For rifampicin, the reduction was sixfold in a study.

{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}

Lurasidone [(3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl) piperazin-1-ylmethyl]-cyclohexylmethyl}-hexahydro-4,7-methano-2Hisoindole-1,3-dione hydrochloride] ]{{Cite web |work=PubChem |publisher=U.S. National Library of Medicine |title=(3aR,4S,7R,7aS)-2-(1R,2R)-2-[[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]methyl]cyclohexyl]methyl]hexahydro-4,7-methano-1H-isoindole-1,3(2H)-dione of the dopamine D₂ and D₃ receptors,{{cite journal | vauthors = Fountoulakis KN, Gazouli M, Kelsoe J, Akiskal H | title = The pharmacodynamic properties of lurasidone and their role in its antidepressant efficacy in bipolar disorder | journal = European Neuropsychopharmacology | volume = 25 | issue = 3 | pages = 335–342 | date = March 2015 | pmid = 25596883 | doi = 10.1016/j.euroneuro.2014.11.010 | s2cid = 25628197 }} and the serotonin 5-HT_2A and 5-HT₇ receptors, and the α_2C-adrenergic receptor, and as a partial agonist of the serotonin 5-HT_1A receptor. It has moderate-affinity antagonism at α2C-adrenergic receptors; low to very low-affinity antagonism at α1A-adrenergic α2A-adrenergic receptors.{{cite journal | vauthors = Franklin R, Zorowitz S, Corse AK, Widge AS, Deckersbach T | title = Lurasidone for the treatment of bipolar depression: an evidence-based review | journal = Neuropsychiatric Disease and Treatment | volume = 11 | pages = 2143–2152 | date = 19 August 2015 | pmid = 26316760 | pmc = 4547662 | doi = 10.2147/NDT.S50961 | doi-access = free }}

It has only low and likely clinically unimportant affinity for the serotonin 5-HT_2C receptor, which may underlie its low propensity for appetite stimulation and weight gain.{{cite journal | vauthors = Samalin L, Ben Gharbia M, Garnier M, Llorca PM | title = [Short-term efficacy and safety of lurasidone in the treatment of schizophrenia] | language = fr | journal = L'Encephale | volume = 40 | issue = 6 | pages = 507–517 | date = December 2014 | pmid = 25453735 | doi = 10.1016/j.encep.2014.10.009 | trans-title = Short-term efficacy and safety of lurasidone in the treatment of schizophrenia }}{{cite journal |vauthors=Lincoln J, Tripathi A |year=2011 |title=Lurasidone for Schizophrenia |journal=Current Psychiatry |volume=10 |issue=1 |pages=67–70 |url=http://www.mdedge.com/currentpsychiatry/article/64162/schizophrenia-other-psychotic-disorders/lurasidone-schizophrenia |access-date=2 October 2016 |archive-date=3 October 2016 |archive-url=https://web.archive.org/web/20161003063328/http://www.mdedge.com/currentpsychiatry/article/64162/schizophrenia-other-psychotic-disorders/lurasidone-schizophrenia |url-status=live }} The drug also has negligible affinity for the histamine H₁ receptor and the muscarinic acetylcholine receptors, and hence has no antihistamine or anticholinergic effects.{{cite journal | vauthors = Ishiyama T, Tokuda K, Ishibashi T, Ito A, Toma S, Ohno Y | title = Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test | journal = European Journal of Pharmacology | volume = 572 | issue = 2–3 | pages = 160–170 | date = October 2007 | pmid = 17662268 | doi = 10.1016/j.ejphar.2007.06.058 }}{{cite journal | vauthors = Greenberg WM, Citrome L | title = Pharmacokinetics and Pharmacodynamics of Lurasidone Hydrochloride, a Second-Generation Antipsychotic: A Systematic Review of the Published Literature | journal = Clinical Pharmacokinetics | volume = 56 | issue = 5 | pages = 493–503 | date = May 2017 | pmid = 27722855 | doi = 10.1007/s40262-016-0465-5 | s2cid = 207485482 }} Drowsiness (somnolence) side effect is not explained by its antagonist activity to histamine.{{cite journal | vauthors = Cruz MP | title = Lurasidone HCl (Latuda), an Oral, Once-Daily Atypical Antipsychotic Agent for the Treatment of Patients with Schizophrenia | journal = P & T | volume = 36 | issue = 8 | pages = 489–492 | date = August 2011 | pmid = 21935296 | pmc = 3171824 }}{{cite journal | vauthors = Corponi F, Fabbri C, Bitter I, Montgomery S, Vieta E, Kasper S, Pallanti S, Serretti A | title = Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone | journal = European Neuropsychopharmacology | volume = 29 | issue = 9 | pages = 971–985 | date = September 2019 | pmid = 31255396 | doi = 10.1016/j.euroneuro.2019.06.008 | hdl = 11585/714012 | s2cid = 195699303 | url = https://kclpure.kcl.ac.uk/portal/en/publications/bf9947d3-f6a6-486d-9420-771d89443f76 | hdl-access = free }}

The relationship between dose and D₂ receptor occupancy levels were 41–43% for 10 mg, 51–55% for 20 mg, 63–67% for 40 mg, 77–84% for 60 mg, and 73–79% for 80 mg.{{cite journal | vauthors = Wong DF, Kuwabara H, Brašić JR, Stock T, Maini A, Gean EG, Loebel A | title = Determination of dopamine D₂ receptor occupancy by lurasidone using positron emission tomography in healthy male subjects | journal = Psychopharmacology | volume = 229 | issue = 2 | pages = 245–252 | date = September 2013 | pmid = 23649882 | doi = 10.1007/s00213-013-3103-z | s2cid = 253737308 }}

File:ID-14283 skeletal.svg. The hydroxylation of the norbornane ring is highlighted.{{cite journal | vauthors = Katteboina MY, Pilli NR, Mullangi R, Seelam RR, Satla SR | title = LC-MS/MS assay for the determination of lurasidone and its active metabolite, ID-14283 in human plasma and its application to a clinical pharmacokinetic study | journal = Biomedical Chromatography | volume = 30 | issue = 7 | pages = 1065–1074 | date = July 2016 | pmid = 26577488 | doi = 10.1002/bmc.3651 }} The other active metabolite, ID-14326, has the OH group in endo position.{{cite journal | vauthors = Caccia S, Pasina L, Nobili A | title = Critical appraisal of lurasidone in the management of schizophrenia | journal = Neuropsychiatric Disease and Treatment | volume = 8 | pages = 155–168 | year = 2012 | pmid = 22570547 | pmc = 3346058 | doi = 10.2147/NDT.S18059 | doi-access = free }}]]

File:ID-11614 and 20219 skeletal.svg produces the metabolites ID-11614 and ID-20219.{{cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000PharmR.pdf|title=Lurasidone pharmacology review|publisher=Center for Drug Evaluation and Research|date=30 December 2009|access-date=2 October 2016|archive-date=3 October 2016|archive-url=https://web.archive.org/web/20161003115210/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000PharmR.pdf|url-status=dead}}]]

Lurasidone is taken by mouth and has an estimated absorption rate of 9 to 19%. Studies have shown that when lurasidone is taken with food, absorption increases about twofold. Peak blood plasma concentrations are reached after one to three hours. About 99% of the circulating substance are bound to plasma proteins.{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002713/WC500164683.pdf|title=Latuda: EPAR – Product Information|publisher=European Medicines Agency|date=14 April 2016|access-date=27 February 2017|archive-date=21 August 2016|archive-url=https://web.archive.org/web/20160821085044/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002713/WC500164683.pdf|url-status=live}} Efficacy data for lurasidone have been evaluated for doses of 20 mg to 120 mg daily.

Lurasidone is extensively metabolised by CYP3A4 leading to contraindication of both strong inhibitors as well as strong inducers of this enzyme,{{Cite web |url=https://www.ema.europa.eu/en/documents/assessment-report/latuda-epar-public-assessment-report_en.pdf |title=European Medicines Agency Assessment report Latuda International non-proprietary name: LURASIDONE Procedure No. EMEA/H/C/002713/0000 |access-date=14 November 2022 |archive-date=14 November 2022 |archive-url=https://web.archive.org/web/20221114022004/https://www.ema.europa.eu/en/documents/assessment-report/latuda-epar-public-assessment-report_en.pdf |url-status=live }} but has negligible affinity to other cytochrome P450 enzymes. It is transported by P-glycoprotein and ABCG2 and also inhibits these carrier proteins in vitro. It also inhibits the solute carrier protein SLC22A1, but no other relevant transporters.{{cite web|url=http://psychotherapeuticdrugs.com/index.php/new-drug-approvals/latuda-lurasidone-hcl|title=Latuda: Prescribing Information|publisher=Psychotherapeutic Drugs|access-date=17 December 2010|archive-url=https://web.archive.org/web/20110628044842/http://psychotherapeuticdrugs.com/index.php/new-drug-approvals/latuda-lurasidone-hcl|archive-date=28 June 2011|url-status=dead}}

Main metabolism pathways are oxidative N-dealkylation between the piperazine and cyclohexane rings, hydroxylation of the norbornane ring, and S-oxidation.^:59 Other pathways are hydroxylation of the cyclohexane ring and reductive cleavage of the isothiazole ring followed by S-methylation. The two relevant active metabolites are the norbornane hydroxylation products called ID-14283 and ID-14326, the former reaching pharmacologically relevant blood plasma concentrations. The two major inactive metabolites are the N-dealkylation products (the carboxylic acid ID-20219 and the piperazine ID-11614), and a norbornane hydroxylated derivative of ID-20219 (ID-20220). Of lurasidone and its metabolites circulating in the blood, the native drug makes up 11%, the main active metabolite 4%, and the inactive carboxylic acids 24% and 11%, respectively. Several dozen metabolites have been identified altogether.^:59–61

Biological half-life is given as 18 hours or 20 to 40 hours in different sources. 80% or 67% of a radiolabelled dose was recovered from the feces, and 9% or 19% from the urine.

Lurasidone was first synthesised circa 2003.{{cite web|url=http://www.mmm-online.com/features/leading-latuda-through-the-crowd/article/213096/|title=Leading Latuda through the crowd|date=1 October 2011|quote=Latuda was developed at an R&D facility established in Fort Lee, NJ, about eight years ago by Sunovion's Japanese parent Dainippon Sumitomo Pharma Co. (DSP).|access-date=25 June 2017|archive-date=28 August 2018|archive-url=https://web.archive.org/web/20180828170409/http://www.mmm-online.com/features/leading-latuda-through-the-crowd/article/213096/|url-status=live}}

Lurasidone is a structural analogue of ziprasidone. Lurasidone shows a very close pharmacological profile and has been synthesized similarly to ziprasidone.{{Cite book|url=https://books.google.com/books?id=A8oHBgAAQBAJ&pg=PA100|title=Synthesis of Best-Seller Drugs|vauthors=Vardanyan R, Hruby V|date=7 January 2016|publisher=Academic Press|via=Google Books|isbn=978-0-12-411524-8|access-date=4 September 2017|archive-date=11 April 2023|archive-url=https://web.archive.org/web/20230411014520/https://books.google.com/books?id=A8oHBgAAQBAJ&pg=PA100|url-status=live}}

Lurasidone is chemically similar to perospirone (also a chemical analogue of ziprasidone), as well as risperidone, paliperidone and iloperidone.{{cite web|url=http://excli.de/vol13/Mauri_13102014_proof.pdf|date=17 November 2016|archive-url=https://web.archive.org/web/20161117142131/http://excli.de/vol13/Mauri_13102014_proof.pdf|archive-date=17 November 2016|title=EXCLI Journal}}

It has approval from the US Food and Drug Administration (FDA) for treating schizophrenia since 2010, and for treating depressive episodes in adults with bipolar I disorder since 2013.

File:Image of Latuda (Lurasidone) bottles.png

In Canada, as of 2014, lurasidone is generally more expensive than risperidone and quetiapine but less expensive than aripiprazole.{{cite book | via = National Center for Biotechnology Information, U.S. National Library of Medicine | chapter = Summary of Pharmacoeconomic Submission | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK195609/ | title = Lurasidone Hydrochloride (Latuda): Management of Manifestations of Schizophrenia | author = Canadian Agency for Drugs and Technologies in Health | access-date = 30 April 2020 | date = 2014 | publisher = Canadian Agency for Drugs and Technologies in Health | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828152151/https://www.ncbi.nlm.nih.gov/books/NBK195609/ | url-status = live }}

In the United States, because a number of doses have the same price per tablet, pill splitting has been used to decrease costs.{{cite journal | vauthors = Carey H, Fondriest M | title = Cost-Savings From an Antipsychotic Tablet-Splitting Program | journal = P & T | volume = 42 | issue = 6 | pages = 384–393 | date = June 2017 | pmid = 28579725 | pmc = 5440099 }} In 2019, generic versions were approved in the United States; however, they only became available in 2023 due to drug patents.{{cite news |vauthors=Hopkins JS |title=Generic-Drug Approvals Soar, But Patients Still Go Without |url=https://www.wsj.com/articles/many-generic-drugs-havent-hit-market-hindering-cost-control-efforts-11574198448 |access-date=30 April 2020 |work=Wall Street Journal |date=19 November 2019 |archive-date=27 April 2020 |archive-url=https://web.archive.org/web/20200427084114/https://www.wsj.com/articles/many-generic-drugs-havent-hit-market-hindering-cost-control-efforts-11574198448 |url-status=live }}

In India, this drug is available under the brand names of Atlura, Lurace, Lurafic, Luramax (Sun Pharma), Lurasid, Lurastar, Latuda, Lurata{{Cite web|url=http://www.mims.com/india/drug/search?q=Lurasidone|title='Lurasidone' drug search|publisher=CIMS India|access-date=21 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828152153/https://www.mims.com/india/drug/search?q=Lurasidone|url-status=live}} and additionally as Alsiva, Emsidon, Lurakem, Luratrend, Tablura, and Unisidon.{{Cite web|url=https://www.ndrugs.com/?s=lurasidone#substitutes|title=Generic Drugs (ndrugs.com)|access-date=30 April 2018|archive-date=1 May 2018|archive-url=https://web.archive.org/web/20180501092921/https://www.ndrugs.com/?s=lurasidone#substitutes|url-status=live}}

Lurasidone was approved in the United States for the treatment of schizophrenia in October 2010{{cite web | title=Drug Approval Package: Latuda (lurasidone hydrochloride) Tablets NDA #200603 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000TOC.cfm | access-date=12 May 2020 | archive-date=25 February 2021 | archive-url=https://web.archive.org/web/20210225053549/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000TOC.cfm | url-status=dead }}{{cite press release | title = FDA approves Latuda to treat schizophrenia in adults | publisher = U.S. Food and Drug Administration (FDA) | date = 28 October 2010 | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm231512.htm | archive-url = https://web.archive.org/web/20101030233353/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm231512.htm | url-status = dead | archive-date = 30 October 2010 | access-date = 29 October 2010}} and for the treatment of depressive episodes associated with bipolar I disorder in June 2013.{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/200603Orig1s010.pdf | title=Latuda Supplement Approval Package 1 | website=U.S. Food and Drug Administration (FDA) | access-date=12 May 2020 | archive-date=27 July 2020 | archive-url=https://web.archive.org/web/20200727025352/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/200603Orig1s010.pdf | url-status=dead }}{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/200603Orig1s011.pdf | title=Latuda Supplement Approval Package 2 | website=U.S. Food and Drug Administration (FDA) | access-date=12 May 2020 | archive-date=28 August 2021 | archive-url=https://web.archive.org/web/20210828152150/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/200603Orig1s011.pdf | url-status=live }} It received regulatory approval in the United Kingdom in September 2014. In October 2014, NHS Scotland advised use of lurasidone for schizophrenic adults who have not seen improvements with previous antipsychotics due to problems that arise from weight gain or changes in metabolic pathways when taking other medications.{{cite web|publisher=Scottish Medicines Consortium|year=2014|title=Lurasidone, 18.5mg, 37mg, 74mg film-coated tablets (Latuda) SMC No. (994/14)|url=http://www.scottishmedicines.org.uk/files/advice/lurasidone__Latuda__FINAL_Sept_2014_amended_15.09.14_for_website.pdf|work=scottishmedicines.org.uk|access-date=7 March 2016|archive-date=8 March 2016|archive-url=https://web.archive.org/web/20160308113939/http://www.scottishmedicines.org.uk/files/advice/lurasidone__Latuda__FINAL_Sept_2014_amended_15.09.14_for_website.pdf|url-status=dead}} The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion for it in January 2014, and it was approved for medical use by the EMA in March 2014.{{cite web | title=Latuda EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/latuda | access-date=12 May 2020 | archive-date=11 August 2020 | archive-url=https://web.archive.org/web/20200811111331/https://www.ema.europa.eu/en/medicines/human/EPAR/latuda | url-status=live }} {{PD-notice}} It was launched in Canada for the treatment of schizophrenia in September 2012, Health Canada giving their Summary Basis of Decision (SBD) as favourable on 15 October 2012.{{cite web|url= http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2012_latuda_145406-eng.php#a2|work= hc-sc.gc.ca|publisher= Health Canada|title= Summary Basis of Decision (SBD) for Latuda|year= 2012|access-date= 19 June 2013|archive-date= 27 June 2013|archive-url= https://web.archive.org/web/20130627090950/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2012_latuda_145406-eng.php#a2|url-status= live}} The European Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults.{{cite web|url=http://www.tpi.takeda.com/media/news-releases/2014/european-marketing-authorization-for-latuda/|title=European Marketing Authorization for Latuda|work=takeda.com|access-date=25 November 2015|archive-url=https://web.archive.org/web/20171226234708/http://www.tpi.takeda.com/media/news-releases/2014/european-marketing-authorization-for-latuda/|archive-date=26 December 2017|url-status=dead}} It is approved for use in the EU.

Generic versions of lurasidone were approved for use in the United States in January 2019 and became available in 2023.{{cite web | title=Lurasidone: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208049 | access-date=12 May 2020 | archive-date=1 October 2020 | archive-url=https://web.archive.org/web/20201001225140/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208049 | url-status=dead }}

{{Reflist}}

• {{cite web | title=FDA Drug Safety Communication: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks | website=U.S. Food and Drug Administration (FDA) | date=7 January 2021 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications | archive-url=https://web.archive.org/web/20190914105148/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications | url-status=dead | archive-date=14 September 2019 }}

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