Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of schizophrenia.
Sertindole is not approved for use in the United States and was discontinued in Australia in January 2014.
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 (<0.1% incidence) adverse effects include:
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 Biologic protein Binding affinity (Ki[nM]) Notes 5-HT1A 280 5-HT1B 60 5-HT1D 96 5-HT1E 430 5-HT1F 360 5-HT2A 0.39 The receptor believed to mediate the atypicality of atypical antipsychotics. 5-HT2C 0.9 Likely responsible for its propensity for causing weight gain. 5-HT6 5.4 5-HT7 28 α1A 1.8 Likely responsible for the orthostatic hypotension seen in patients on sertindole. α2A 640 α2B 450 α2C 450 β1 5000 β2 5000 M1 >10000 M3 2692 D2 2.35 Believed to be responsible for the drug's efficacy against positive symptoms. D3 2.30 D4 4.92 hERG 3 Responsible for the QT interval prolongation and torsade de pointes H1 130 NK1 1000
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,Zeneca's Seroquel Nears Market Approval - The Pharma Letter, 16 July 1997 but withdrew this application in 1998 following concerns over the increased risk of sudden death from QTc prolongation.Abbott Labs Withdraws Sertindole NDA Sertindole - The Pharma Letter, 12 January 1998 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.FDA Advisory Committee provides opinion on Serdolect for the treatment of schizophrenia - Lundbeck press release, 8 April 2009 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.Food and Drug Administration; Minutes of the Psychphamacological Drugs Advisory Committee, 7 Apr 2009 , 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 1998EU CHMP recommends lifting ban on atypical antipsychotic Serdolect (sertindole) - National electronic Library for Medicines, NHS 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.COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS OPINION FOLLOWING AN ARTICLE 36 REFERRAL: SERTINDOLE - European Medicines Agency, 13 September 2002Restricted re-introduction of the atypical antipsychotic sertindole (Serdolect) - MHRA, 2002 , sertindole is authorized in several member states of the European Union.
See also Piperidinylindole
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