Lurasidone was approved for medical use in the United States in 2010. In 2019 generic versions were approved in the United States but will not be available until 2023. In 2018, it was the 245th most commonly prescribed medication in the United States, with more than 2million prescriptions.
In the United States, lurasidone is indicated for the treatment of:
Schizophrenia in adults and adolescents (13 to 17 years)
Depressive episode associated with bipolar I disorder in adults and pediatric patients (10 to 17 years) as monotherapy
Depressive episode associated with bipolar I disorder in adults as adjunctive therapy with lithium or valproate
In the European Union, lurasidone is indicated for the treatment of schizophrenia in adults aged 18 years and over, but not for bipolar disorder.
A 2014 review found lurasidone to be similar in effectiveness to other atypical antipsychotics. A 2013 review of 15 antipsychotic medications in schizophrenia found lurasidone demonstrated mild effectiveness. It is considered to be as effective as iloperidone, and 13 to 15% less effective than ziprasidone, chlorpromazine, and asenapine.
In July 2013, lurasidone received approval for bipolar I depression. Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions being quetiapine,olanzapine and possibly asenapine) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significant antimanic activity, 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."
Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.
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; however, these risks are not likely to be greater than those associated with antipsychotics of other classes. Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with antipsychotic use.
Weight gain is reported in up to 15 and 16 percent of users.
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. 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. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.
Blood plasma concentrations may be increased when combined with CYP3A4 inhibitors, 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 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.
The main inactivation step by oxidative N-dealkylation produces the metabolites ID-11614 and ID-20219.
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.
Lurasidone is mainly metabolized in the liver via the enzyme CYP3A4, 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.
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
In the US, because a number of doses have the same price per tablet, pill splitting has been used to decrease costs. In 2019 generic versions were approved in the United States; however, they will not be available until 2023.
In India, this drug is available under the brand names of Atlura, Lurace, Lurafic, Luramax, Lurasid, Lurastar, Latuda, Lurata and additionally as Alsiva, Emsidon, Lurakem, Luratrend, Tablura, and Unison.
Lurasidone was approved in the United States for the treatment of schizophrenia in October 2010 and for the treatment of depressive episodes associated with bipolar I disorder in June 2013. 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. 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. 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. European Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults. It is approved for use in the EU.
Generic versions of lurasidone were approved for use in the United States in January 2019.
^Information, National Center for Biotechnology; Pike, U. S. National Library of Medicine 8600 Rockville; MD, Bethesda; Usa, Bethesda (2014). KEY LIMITATIONS. Canadian Agency for Drugs and Technologies in Health. Retrieved 30 April 2020.
^ abLeucht 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 (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–62. doi:10.1016/S0140-6736(13)60733-3. PMID23810019. S2CID32085212.
^Young AH, McElroy SL, Bauer M, Philips N, Chang W, Olausson B, Paulsson B, Brecher M, et al. (EMBOLDEN I (Trial 001) Investigators) (February 2010). "A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I)". The Journal of Clinical Psychiatry. 71 (2): 150–62. doi:10.4088/JCP.08m04995gre. PMID20122369.
^Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D (February 2010). "Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression". Journal of Affective Disorders. 121 (1–2): 106–15. doi:10.1016/j.jad.2009.10.007. PMID19903574.
^Tohen M, Katagiri H, Fujikoshi S, Kanba S (July 2013). "Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies". Journal of Affective Disorders. 149 (1–3): 196–201. doi:10.1016/j.jad.2013.01.022. PMID23485111.
^Corya SA, Perlis RH, Keck PE, Lin DY, Case MG, Williamson DJ, Tohen MF (May 2006). "A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression". The Journal of Clinical Psychiatry. 67 (5): 798–806. doi:10.4088/JCP.v67n0514. PMID16841630.
^Azorin JM, Sapin C, Weiller E (February 2013). "Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: results from post hoc analyses". Journal of Affective Disorders. 145 (1): 62–9. doi:10.1016/j.jad.2012.07.013. PMID22868059.
^Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR (October 2011). "Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis". Lancet. 378 (9799): 1306–15. doi:10.1016/S0140-6736(11)60873-8. PMID21851976. S2CID25512763.
^ACOG Committee on Practice Bulletins--Obstetrics (April 2008). "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". Obstetrics and Gynecology. 111 (4): 1001–20. doi:10.1097/AOG.0b013e31816fd910. PMID18378767.
^Moore TA (April 2011). "Schizophrenia treatment guidelines in the United States". Clinical Schizophrenia & Related Psychoses. 5 (1): 40–9. doi:10.3371/CSRP.5.1.6. PMID21459738.
^Joint Formulary Committee, BMJ, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN978-0-85369-845-6. 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.
^Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
^ abcdefghijklmnopqrsIshibashi T, Horisawa T, Tokuda K, Ishiyama T, Ogasa M, Tagashira R, Matsumoto K, Nishikawa H, Ueda Y, Toma S, Oki H, Tanno N, Saji I, Ito A, Ohno Y, Nakamura M (July 2010). "Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity". The Journal of Pharmacology and Experimental Therapeutics. 334 (1): 171–81. doi:10.1124/jpet.110.167346. PMID20404009. S2CID12893717.
^ abIshiyama T, Tokuda K, Ishibashi T, Ito A, Toma S, Ohno Y (October 2007). "Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test". European Journal of Pharmacology. 572 (2–3): 160–70. doi:10.1016/j.ejphar.2007.06.058. PMID17662268.
^Samalin L, Ben Gharbia M, Garnier M, Llorca PM (December 2014). "[Short-term efficacy and safety of lurasidone in the treatment of schizophrenia]" [Short-term efficacy and safety of lurasidone in the treatment of schizophrenia]. L'Encephale (in French). 40 (6): 507–17. doi:10.1016/j.encep.2014.10.009. PMID25453735.
^Greenberg WM, Citrome L (May 2017). "Pharmacokinetics and Pharmacodynamics of Lurasidone Hydrochloride, a Second-Generation Antipsychotic: A Systematic Review of the Published Literature". Clinical Pharmacokinetics. 56 (5): 493–503. doi:10.1007/s40262-016-0465-5. PMID27722855. S2CID207485482.
^Information, National Center for Biotechnology; Pike, U. S. National Library of Medicine 8600 Rockville; MD, Bethesda; Usa, Bethesda (2014). SUMMARY OF PHARMACOECONOMIC SUBMISSION. Canadian Agency for Drugs and Technologies in Health.