Sertindole, sold under the brand name Serdolect among others, is an

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by

Abbott Labs Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...

. Like other

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

s, it has activity at

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

receptors in the brain. It is used in the treatment of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

. It is classified chemically as a phenylindole derivative. 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 Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

quetiapine Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...

, and

aripiprazole Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...

, as effective as

ziprasidone Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitati ...

, approximately as effective as

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

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 nd non-significantlymore sedation than

amisulpride Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold un ...

and

paliperidone Paliperidone, sold under the trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals. An extended release formulation is a ...

) * Ejaculation disorder * Erectile dysfunction * Orthostatic hypotension * Weight gain (which it seems to possess a similar propensity for causing as

) Uncommon (0.1–1% incidence) adverse effects include: * Substernal chest pain * Face oedema *

Influenza-like illness Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...

* Neck rigidity * Pallor * Peripheral vascular disorder * syncope *

Torsades de pointes ''Torsades de pointes, torsade de pointes'' or ''torsades des pointes'' (TdP) (, , translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia t ...

* Vasodilation *

Suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...

attempt *

Amnesia Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...

Anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

* 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 Galactorrhea ( also spelled galactorrhoea) ( galacto- + -rrhea) or lactorrhea ( lacto- + -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing. Galactorrhea is reported to occur in 5–32% of women. M ...

Rare (<0.1% incidence) adverse effects include: *

Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fa ...

Tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

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.

Safety and status

United States

first applied for U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) approval for sertindole in 1996, but withdrew this application in 1998 following concerns over the increased risk of sudden death from

QTc prolongation QT prolongation is a measure of delayed ventricular repolarisation, which means the heart muscle takes longer than normal to recharge between beats. It is an electrical disturbance which can be seen on an electrocardiogram (ECG). Excessive QT prolo ...

.Abbott Labs Withdraws Sertindole NDA Sertindole
- The Pharma Letter, 12 Jan 1998 In a trial of 2000 patients on taking sertindole, 27 patients died unexpectedly, including 13 sudden deaths.{{cite web , url=http://apps.who.int/medicinedocs/en/d/Js2256e/1.12.html#Js2256e.1.12 , archive-url=https://web.archive.org/web/20110622124240/http://apps.who.int/medicinedocs/en/d/Js2256e/1.12.html#Js2256e.1.12 , url-status=dead , archive-date=June 22, 2011 , title=WHO Pharmaceuticals Newsletter 1998, No. 03&04: Regulatory actions: Sertindole - approval application withdrawn 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 Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions ...

. 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. {{Asof, October 2010, the drug has not been approved by the FDA for use in the USA.{{failed verification, date=September 2020

European Union

In the European Union, sertindole was approved and marketed in 19 countries from 1996, but its marketing authorization was suspended by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...

in 1998 and the drug was withdrawn from the market. In 2002, based on new data, the EMA's 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. {{As of, September 2020, sertindole is authorized in several states of the European Union.{{cite report , url=https://www.ema.europa.eu/documents/psusa/sertindole-list-nationally-authorised-medicinal-products-psusa/00002695/202001_en.pdf , title=Sertindole: List of nationally authorised medicinal products - PSUSA/00002695/202001 , date=3 September 2020 , id=EMA/270645/2015 , publisher=

(EMA)

References

{{reflist

External links

* {{cite web , url = https://druginfo.nlm.nih.gov/drugportal/name/sertindole , publisher = U.S. National Library of Medicine , work = Drug Information Portal , title = Sertindole {{Antipsychotics {{Navboxes , title =

Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

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