Among the different mental disorders and alterations, schizophrenia is probably one of the most disturbing for the person who suffers it, since it produces a rupture or split between the psyche and reality.

Although there is currently no treatment that eliminates and cures this condition, fortunately we do have different methods and treatments that allow us to prevent and control the symptoms. One of the pillars of these treatments are neuroleptic psychopharmaceuticals or antipsychotics, of which there is a wide variety.

Among these drugs developed to treat this problem we find sertindole, which we will talk about throughout this article .

What is sertindole?

It is called sertindole , a psychoactive drug belonging to the group of antipsychotics or neuroleptics , which are substances that act on the body by modifying brain chemistry in such a way that they reduce or eliminate psychotic symptoms while they are in effect, especially at the level of symptoms such as hallucinations, delusions and agitation.

It is an effective drug derived from phenylindol , which also has the advantage over other neuroleptics that it does not generate, or at least not as frequently, the same level of sedation as other drugs of the same type or as many extrapyramidal or motor symptoms. It is available in pharmacy in the form of film-coated tablets, for oral administration.

Within the antipsychotics sertindole is classified as atypical or second generation. This group of drugs was designed with the purpose of being effective not only against the so-called positive symptomatology of schizophrenia and other psychotic disorders, that is, the symptoms that add some element to the patient’s activity, such as the aforementioned hallucinations and delusions (something for which the first generation antipsychotics were already effective); they were also intended to have a therapeutic effect on the negative symptomatology, which implies the loss or decrease of the subject’s abilities.

It is also sought that they do so safely and generating as few side effects as possible (the first generation generated a large number of possible annoying side effects and in some cases could be dangerous).

Sertindole was withdrawn from sale in Spain during 1998 due to indications of a possible link between the consumption of the drug and some cases of heart problems and deaths in the United Kingdom, but after eight years of analysis and clinical studies it was decided to lift the ban as no increase in the risk of mortality was observed in the general population. However, it was decided to include the population with cardiac problems among the group of people who are contraindicated to the drug, and it is necessary to maintain medical monitoring of the patient’s condition and evolution .

Mechanism of action of this substance

The mechanism of action of sertindole, i.e. the way it affects the body, is based on the action on certain neurotransmitters.

Specifically, sertindole acts as a dopamine antagonist at its D2 receptors , that is, it blocks and hinders the action of dopamine and decreases its concentration in the brain. This action would be the one that generates a decrease in positive symptomatology, since an excess of dopamine has been observed in the mesolimbic pathway of people with this type of symptomatology.

In addition to this it is also an antagonist of the serotonin 5-HT2 receptor and the alpha1 adrenergic . In this sense it has a long-lasting effect.

Being a serotonin antagonist, which itself inhibits dopamine synthesis, makes it effective in the treatment of negative symptoms and generates fewer side effects than classical neuroleptics. The reason for this is that while positive symptoms are generated by an excess of dopamine in the mesolimbic pathway, negative symptoms have been associated with a deficit of it in the mesocortical pathway.

Serotonin is a dopamine inhibitor and its receptors are found in a high proportion in the cortex, so by inhibiting the inhibitor the dopamine levels in this area do not decrease and even increase (while they do go down where they have to, in the mesolimbic pathway).

What disorders is it indicated for?

Sertindole is a useful drug, and as an antipsychotic or neuroleptic its main therapeutic indication is in the treatment of schizophrenia .

However, due to the existence of cardiovascular risk, it is not a treatment of choice, and is currently only used when there is no response or intolerance to other antipsychotic drugs and provided that acute and emergency symptoms are not present. If used, the patient must be monitored and regularly checked.

Possible side effects

Although sertindole is a useful drug in the treatment of schizophrenia, the administration of this substance can generate annoying and even dangerous side effects .

Among the most frequent we can find dizziness, nasal congestion, hypotension, tingling or paresthesia, weight gain or dry mouth .

In addition, although less commonly, hyperglycemia, loss of consciousness, seizures, tardive dyskinesia, ejaculation difficulties (reduced volume of ejaculated fluid) and/or erectile dysfunction, peripheral edema

may occur

Among the frequent ones, one of the most dangerous, and the reason why it was removed, is in the increased risk of cardiac events : the QT interval is prolonged, which facilitates the possible appearance of arrhythmias in at-risk populations.

Torsade de Pointes arrhythmias may also occur, in which there is ventricular tachycardia and drop in blood pressure (can cause fainting and, in complex cases, even death). Another possibility is the appearance of thrombosis and venous or pulmonary embolisms, although this is not usual. Finally, there is a risk of neuroleptic malignant syndrome, which is also potentially fatal.

Contraindications

Although this drug may be beneficial for the treatment of certain pathologies, the truth is that we must also take into account that the effect of sertindole on the organism may be dangerous for some sectors of the population. In this sense, we can find that some people have contraindicated this drug.

People who are allergic to sertindole should not take it. Due to the cardiovascular risk, this drug is contraindicated for those who have suffered some type of coronary or cerebrovascular event . It is also contraindicated in people with severe liver failure.

Pregnant and lactating women should avoid consumption, and in the case of the latter if there is no other option, lactation should be cut off. It is also not indicated in the infant stage.

This should be avoided or at least maximized for people who have diabetes or have had seizures, as well as for those who are taking other drugs including examples of some antidepressants, antiarrhythmics, other antipsychotics or even antibiotics and antihistamines (the adequacy and possible interaction between drugs should be medically evaluated).

Bibliographic references:

  • Spanish Agency for Medicines and Healthcare Products (2015). Technical File. Serdolect. Sertindol 4 mg-20 mg film-coated tablets. Available at: https://cima.aemps.es/cima/pdfs/es/ft/61582/61582_ft.pdf.
  • Lewis, R., Bagnall, A.-M., Leitner,M. (2005). Sertindol for schizophrenia. Cochrane Database of Systematic Reviews. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001715.pub2/full/es.
  • Vidal Vademecum (2016) Sertindol. [Online]. Available at: https://www.vademecum.es/principios-activos-sertindol-n05ae03.