Zuclopenthixol: characteristics and side effects of this drug.

A review of the effects and functions of zuclopenthixol, a typical antipsychotic.

Antipsychotic drugs have been used for decades as a treatment for schizophrenia and psychotic symptoms, and over the years they have evolved.

The first generation of these drugs, the typical neuroleptics, were effective in alleviating the positive symptoms of psychosis (such as delusions and hallucinations), but less so for the negative symptoms (anhedonia, abulia or affective dullness). An example of this group of drugs is zuclopenthixol, which we will discuss throughout the article.

Below we will explain What are the characteristics and medical uses of zuclopenthixol?The main features of these drugs are their mechanism of action, the main side effects and contraindications, and their clinical efficacy compared with the group of second-generation antipsychotics.

Zuclopenthixol: characteristics and medical uses.

Zuclopenthixol is a drug of the group of typical antipsychotic drugs.It is derived from thioxanthene and is used in the treatment of schizophrenia and other psychoses. This drug was introduced on the market in 1978 and is currently available in various forms, mainly intramuscular injections and tablets.

Over the years, several generations of neuroleptic drugs have been developed and marketed; the first generation, known as typical antipsychotics, includes zuclopenthixol (from the phenothiazine group) and other classic neuroleptics such as haloperidol and chlorpromazine.

This first generation of drugs for the treatment of psychosis was gradually replaced by second generation atypical antipsychotics (such as olanzapine or risperidone), with fewer adverse reactions and a more marked effect on the negative symptoms of diseases such as schizophrenia (symptoms including anhedonia, abulia or affective dullness).

Currently, zuclopenthixol is marketed in Spain under the name Clopixolin injectable solutions, ampoules, oral drops and tablets. It is indicated for schizophrenic patients with acute crises, especially with symptoms of agitation and/or depression. Injection is usually the most commonly used route of administration, since it slowly releases the active ingredient and prevents psychotic symptoms from reappearing in the patient. It is usually administered every 1-4 weeks.

Mechanism of action

The mechanism of action of zuclopenthixol is similar to that of the vast majority of typical antipsychotics. This drug exerts an antagonistic action on dopaminergic D1 and D2 receptors, although it acts preferentially on the latter.receptors, although it acts preferentially on the latter. It also has a high affinity for α1-adrenergic receptors and serotonin 5-HT2 receptors.

In addition, zuclopenthixol has mild histamine H1 receptor blocking activity, and also poor affinity for muscarinic cholinergic and α2-adrenergic receptors. It is known that cytochrome P450 2D6 is responsible for metabolizing this drug, in addition to many other commonly used drugs.

The oral bioavailability of zuclopenthixol is 40%, and it reaches its maximum concentration in Blood plasma at 4 hours. It should be noted that food intake does not interfere with its absorption.. In the case of intramuscular injection, the maximum plasma concentration occurs after 24-48 hours (in its acetate form), and after 3-7 days (in its decanoate form).

Contraindications

The use of zuclopenthixol is contraindicated in acute intoxications with alcohol, barbiturates and opiates, comatose states, circulatory collapse, hypersensitivity to thioxanthenes, central nervous system depression, blood dyscrasias or medullary depression, pheochromocytoma, porphyrias, glaucoma, risk of urinary retention in urethroprostatic persons and hepatic and/or renal insufficiency.

Patients with cardiovascular disorders should take special cautionsince the use of zuclopenthixol may cause hypotension and arrhythmias. In people with respiratory problems or asthma, this drug may produce depressive effects on respiratory function. Epileptic patients should also be cautious, because this drug may lower the seizure threshold, especially in high-risk individuals.

Side effects

The use of zuclopenthixol can have a number of side effects and adverse reactions that should be taken into consideration.. Among the most worrying are: neuroleptic malignant syndrome, which is characterized by psychic disturbances, muscular rigidity, hyperthermia and symptoms of hyperactivity of the autonomic nervous system; and extrapyramidal syndrome, which affects the patient's motor skills and causes several characteristic symptoms.

The following are the main organic and psychiatric alterations associated with zuclopenthixol consumption.

Neurological alterations

Frequently (more than 10%), tremor, muscle rigidity, parkinsonism, akathisia, dystonia and dizziness may occur. Occasionally (less than 10%) paresthesia, dyskinesia, tardive dyskinesia and headache may occur.

Psychological/psychiatric disturbances

Frequently, the use of zuclopenthixol can lead to sleep disorders, such as drowsiness problemsand, occasionally, disorders such as asthenia and mental confusion.

Digestive disturbances

One of the most frequent digestive symptoms is dry mouth. In addition, and occasionally, patients using zuclopenthixol may experience dyspepsia, nausea and constipation after consumption.

Cardiovascular alterations

The consumption of zuclopenthixol may occasionally cause tachycardia and hypotension..

Ocular alterations

Occasionally, the use of this drug may cause ocular accommodation disorders.

Other alterations

The use of zuclopenthixol occasionally leads to urinary retentionand, in addition, excessive sweating may occur in some patients.

Clinical efficacy

As mentioned at the beginning, zuclopenthixol belongs to the group of typical antipsychotics, the first generation of drugs used for the treatment of psychotic symptoms mainly in patients with schizophrenia. Since the appearance on the market of second-generation antipsychotics, the prescription of typical neuroleptics for schizophrenic patients has been considerably reduced..

In a review of several studies comparing the clinical efficacy of typical antipsychotics (TA) versus atypical or second generation antipsychotics (AA), it was found that AA were not superior to TA in efficacy or tolerability. In another meta-analysis, it was observed that AT used at optimal doses did not have a higher risk of causing extrapyramidal symptoms than AA, although a lower efficacy was observed.

The CATIE study, which evaluated the efficacy of antipsychotic treatments (using AT and AA) in 1,493 patients with schizophrenia, showed that these drugs had rather moderate efficacy in treating this disease. In addition, lack of efficacy or the occurrence of side effects caused 74% of the patients to drop out of the study before its completion.

The study authors concluded that olanzapine (AA) was the most effective of the antipsychotics studied and that there were no differences among the others (including zuclopenthixol). However, the greater efficacy of olanzapine was offset by an increase in metabolic adverse effects.. In any case, such a high withdrawal rate is evidence of the limitations of antipsychotics (whether AT or AA) in terms of efficacy and safety in the treatment of schizophrenia.