Sertindole, sold under the brand nameSerdolect among others, is anantipsychotic medication. Sertindole was developed by the Danish pharmaceutical companyLundbeck and marketed under license byAbbott Labs. Like otheratypical antipsychotics, it has activity atdopamine andserotonin receptors in the brain. It is used in the treatment ofschizophrenia.
Sertindole is not approved for use in the United States and was discontinued in Australia in January 2014.[citation needed]
Sertindole appears effective as an antipsychotic in schizophrenia.[4] In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, sertindole was found to be slightly less effective thanhaloperidol,quetiapine, andaripiprazole, as effective asziprasidone, approximately as effective aschlorpromazine andasenapine, and slightly more effective thanlurasidone andiloperidone.[5]
Very common (>10% incidence) adverse effects include:[2]
Headache
Ejaculation failure
Insomnia
Dizziness
Common (1–10% incidence) adverse effects include:[2]
Urine that tests positive for red and/or white blood cells
Sedation (causes less sedation than most antipsychotic drugs according to a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs. Causes only slightly [and non-significantly] more sedation thanamisulpride andpaliperidone)[5][6]
Extrapyramidal side effects (EPSE; e.g. dystonia, akathisia, muscle rigidity, parkinsonism, etc. These adverse effects are probably uncommon/rare according to a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs which found it had the 2nd lowest effect size for causing EPSE)[5]
Venous thromboembolism
QT interval prolongation (probably common; in a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs it was found to be the most prone to causing QT interval prolongation)[5]
Sertindole is metabolized in the body to dehydrosertindole.[9] Sertindole has also been reported to interact withtubulin and inhibit its polymerization.[10]
Abbott Labs first applied for USFood and Drug Administration (FDA) approval for sertindole in 1996,[12] but withdrew this application in 1998 following concerns over the increased risk of sudden death fromQTc prolongation.[13] In a trial of 2000 patients on taking sertindole, 27 patients died unexpectedly, including 13 sudden deaths.[14] Lundbeck cites the results of the Sertindole Cohort Prospective (SCoP) study of 10,000 patients to support its claim that although sertindole does increase the QTc interval, this is not associated with increased rates of cardiac arrhythmias, and that patients on sertindole had the same overall mortality rate as those onrisperidone.[15] Nevertheless, in April 2009, an FDA advisory panel voted 13-0 that sertindole was effective in the treatment of schizophrenia but 12-1 that it had not been shown to be acceptably safe.[16] As of October 2010[update], the drug has not been approved by the FDA.[17][failed verification]
In the European Union, sertindole was approved and marketed in 19 member states from 1996,[14] but its marketing authorization was suspended by theEuropean Medicines Agency (EMA) in 1998[18] and the drug was withdrawn from the market. In 2002, based on new data, the EMA'sCommittee for Medicinal Products for Human Use (CHMP) suggested that Sertindole could be reintroduced for restricted use in clinical trials, with strong safeguards including extensive contraindications and warnings for patients at risk of cardiac dysrhythmias, a recommended reduction in maximum dose from 24 mg to 20 mg in all but exceptional cases, and extensive ECG monitoring requirement before and during treatment.[19][20] As of September 2020[update], sertindole is authorized in several member states of the European Union.[21]
^abKaramatskos E, Lambert M, Mulert C, Naber D (November 2012). "Drug safety and efficacy evaluation of sertindole for schizophrenia".Expert Opinion on Drug Safety.11 (6):1047–62.doi:10.1517/14740338.2012.726984.PMID22992213.S2CID11339387.
^abcdefLeucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (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.
^abTaylor D, Paton C, Shitij K (2012).The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell.ISBN978-0-470-97948-8.
^Roth BL, Driscol J (12 January 2011)."PDSP Ki Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived fromthe original on 8 November 2013. Retrieved27 October 2013.
^Baksheeva VE, La Rocca R, Allegro D, Derviaux C, Pasquier E, Roche P, et al. (2025). "NanoDSF Screening for Anti-tubulin Agents Uncovers New Structure–Activity Insights".Journal of Medicinal Chemistry.doi:10.1021/acs.jmedchem.5c01008.
