Sertindole

Medical uses

Sertindole appears effective as an antipsychotic in schizophrenia. 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 than haloperidol, quetiapine, and aripiprazole, as effective as ziprasidone, approximately as effective as chlorpromazine and asenapine, and slightly more effective than lurasidone and iloperidone.

Adverse effects

Very common (10% incidence) adverse effects include:

• Headache
• Ejaculation failure
• Insomnia
• Dizziness

Common (1–10% incidence) adverse effects include:

• 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 than amisulpride and paliperidone)
• Ejaculation disorder
• Erectile dysfunction
• Orthostatic hypotension
• Weight gain (which it seems to possess a similar propensity for causing as quetiapine)

Uncommon (0.1–1% incidence) adverse effects include:

• Substernal chest pain
• Face oedema
• Influenza-like illness
• Neck rigidity
• Pallor
• Peripheral vascular disorder
• syncope
• Torsades de pointes
• Vasodilation
• Suicide attempt
• Amnesia
• Anxiety
• Ataxia
• Confusion
• Incoordination
• Libido decreased
• Libido increased
• Miosis
• Nystagmus
• Personality disorder
• Psychosis
• Reflexes decreased
• Reflexes increased
• Stupor
• Suicidal tendency
• Urinary retention
• Vertigo
• Diabetes mellitus
• Abnormal stools
• Gastritis
• Gingivitis
• Glossitis
• Increased appetite
• Mouth ulceration
• Rectal disorder
• Rectal haemorrhage
• Stomatitis
• Tongue disorder
• Ulcerative stomatitis
• Anaemia
• Ecchymosis
• Hypochromic anaemia
• Leukopenia
• Hyperglycaemia
• Hyperlipemia
• Oedema
• Bone pain
• Myasthenia
• Twitching
• Bronchitis
• Hyperventilation
• Pneumonia
• Sinusitis
• Furunculosis
• Herpes simplex
• Nail disorder
• Psoriasis
• Pustular Rash
• Skin discolouration
• Skin hypertrophy
• Skin ulcer
• Abnormal vision
• Keratoconjunctivitis
• Lacrimation disorder
• Otitis externa
• Pupillary disorder
• Taste perversion
• Anorgasmia
• Penis disorder (gs)
• Urinary urgency
• Hyperprolactinaemia (which it seems to cause with a higher propensity than most other atypical antipsychotics do)
• Seizures
• Galactorrhoea

**Rare (

• Neuroleptic malignant syndrome
• Tardive dyskinesia

Unknown frequency adverse events include:

• 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)
• 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)

Pharmacology

Sertindole is metabolized in the body to dehydrosertindole. Sertindole has also been reported to interact with tubulin and inhibit its polymerization.

Chemistry

In terms of chemical structure, sertindole is a piperidinylindole.

Safety and status

United States

Abbott Labs first applied for US Food and Drug Administration (FDA) approval for sertindole in 1996, but withdrew this application in 1998 following concerns over the increased risk of sudden death from QTc prolongation. In a trial of 2000 patients on taking sertindole, 27 patients died unexpectedly, including 13 sudden deaths. 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 on risperidone. 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. , the drug has not been approved by the FDA.

European Union

In the European Union, sertindole was approved and marketed in 19 member states from 1996, but its marketing authorization was suspended by the European Medicines Agency (EMA) in 1998 and the drug was withdrawn from the market. In 2002, based on new data, the EMA's Committee 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. , sertindole is authorized in several member states of the European Union.

References

References

1. (November 2012). "Drug safety and efficacy evaluation of sertindole for schizophrenia". Expert Opinion on Drug Safety.
2. (May 2011). "Sertindole in the management of schizophrenia". Journal of Central Nervous System Disease.
3. (July 2005). "Sertindole for schizophrenia". The Cochrane Database of Systematic Reviews.
4. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet.
5. (16 January 2013). "PRODUCT INFORMATION SERDOLECT TABLETS". Lundbeck Australia Pty Ltd.
6. (2012). "The Maudsley prescribing guidelines in psychiatry". Wiley-Blackwell.
7. (12 January 2011). "PDSP K_i Database". University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.
8. (2010). "Goodman and Gilman's The Pharmacological Basis of Therapeutics". McGraw-Hill Professional.
9. "TRC {{pipe}} Details of CAS = 173294-84-3, ChemicalName = Dehydrosertindole, synonym = 1-[2-[4-[5-Chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl]-1,3-dihydro-2H-Imidazol-2-one; Lu 28-092, MolFormula = {{chem".
10. (2025). "NanoDSF Screening for Anti-tubulin Agents Uncovers New Structure–Activity Insights". Journal of Medicinal Chemistry.
11. "Sertindole".
12. [http://www.thepharmaletter.com/file/57165/zenecas-seroquel-nears-market-approval.html Zeneca's Seroquel Nears Market Approval] - The Pharma Letter, 16 July 1997
13. [http://www.thepharmaletter.com/file/65187/abbott-labs-withdraws-sertindole-nda.html Abbott Labs Withdraws Sertindole NDA Sertindole] - The Pharma Letter, 12 January 1998
14. "WHO Pharmaceuticals Newsletter 1998, No. 03&04: Regulatory actions: Sertindole - approval application withdrawn".
15. [http://sweden.lundbeck.com/investor/releases/ReleaseDetails/Release_1304142_EN.asp FDA Advisory Committee provides opinion on Serdolect for the treatment of schizophrenia] {{webarchive. link. (14 July 2011 - Lundbeck press release, 8 April 2009)
16. [https://web.archive.org/web/20100203094842/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM198218.pdf Food and Drug Administration; Minutes of the Psychphamacological Drugs Advisory Committee, 7 Apr 2009]
17. "Welcome to Lundbeck's global site".
18. [http://www.nelm.nhs.uk/en/NeLM-Area/News/483119/483386/483398/ EU CHMP recommends lifting ban on atypical antipsychotic Serdolect (sertindole)] {{webarchive. link. (2 October 2011 - National electronic Library for Medicines, NHS)
19. [http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Sertindole_36/WC500011855.pdf COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS OPINION FOLLOWING AN ARTICLE 36 REFERRAL: SERTINDOLE] {{Webarchive. link. (4 March 2016 - European Medicines Agency, 13 September 2002)
20. [http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON019523 Restricted re-introduction of the atypical antipsychotic sertindole (Serdolect)] {{webarchive. link. (17 November 2010 - [[Medicines and Healthcare products Regulatory Agency). MHRA]], 2002
21. (3 September 2020). "Sertindole: List of nationally authorised medicinal products - PSUSA/00002695/202001". [[European Medicines Agency]] (EMA).