Zuclopenthixol: characteristics and side effects of this drug

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

The first generation of these drugs, the typical neuroleptics, were effective in alleviating the positive symptoms of psychosis (such as delusions and hallucinations), but not so much in terms of negative symptoms (anhedonia, apathy or dullness affective). An example of this group of drugs is zuclopenthixol, which we will talk about throughout the article.

Here we explain what are the characteristics and medical uses of zuclopenthixol, its mechanism of action, the main side effects and contraindications, and its clinical efficacy compared to the group of second-generation antipsychotics.

• Related article: "Types of antipsychotics (or neuroleptics)"

Zuclopenthixol: characteristics and medical uses

Zuclopenthixol is a drug from the group of typical antipsychotics, derived from thioxanthene, which is used in the treatment of schizophrenia and other psychoses. This drug was introduced to 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 of these, known as typical antipsychotics, includes zuclopentixol (from group of phenothiazines) and other classic neuroleptics such as haloperidol and chlorpromazine.

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

Currently, zuclopentixol It is marketed in Spain under the name Clopixol, in injectable solutions, ampoules, oral drops and tablets. It is indicated for schizophrenic patients with acute attacks, especially with symptoms of agitation and / or depression. Normally, the most used route of administration is injection, since it slowly releases the active principle and prevents psychotic symptoms from reappearing in the patient. It is usually given 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 dopamine receptors D1 and D2, although it acts preferentially on the latter. It also has a high affinity for α1 adrenergic receptors and 5-HT2 serotonin receptors.

Furthermore, zuclopenthixol has mild histamine H1 receptor blocking activity, and also poor affinity for muscarinic cholinergic and α2 adrenergic receptors. Cytochrome P450 2D6 is known to be 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 after 4 hours. It should be noted that ingestion of food 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).

• You may be interested: "Types of psychotropic drugs: uses and side effects"

Contraindications

The consumption of zuclopentixol is contraindicated in acute intoxication with alcohol, barbiturates and opiates, comatose states, circulatory collapse, hypersensitivity to thioxanthenes, central nervous system depression, blood dyscrasias or depression medullary, pheochromocytoma, porphyrias, glaucoma, risk of urinary retention in uretroprostatic people and liver failure and / or renal.

Patients with cardiovascular disorders should exercise special caution, since the use of zuclopenthixol can cause hypotension and arrhythmias. In people with breathing problems or asthma, this medicine can have depressant effects on respiratory function. Epileptic patients should also exercise caution, since this drug can lower the seizure threshold, especially in high-risk people.

Side effects

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

Let's see below what are the main organic and psychiatric disorders associated with the consumption of zuclopentixol.

Neurological disorders

Frequently (more than 10%), there may be tremors, muscle stiffness, parkinsonism, akathisia, dystonia, and dizziness. Occasionally (less than 10%) paresthesia, dyskinesia, tardive dyskinesia, and headache may occur.

Psychological / psychiatric disorders

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

Digestive disorders

One of the most common digestive symptoms is dry mouth. In addition, and occasionally, patients who use zuclopenthixol may suffer dyspepsia, nausea and constipation after consumption.

Cardiovascular disorders

Consumption of zuclopenthixol can occasionally cause tachycardia and hypotension.

Eye disorders

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

Other alterations

The use of zuclopenthixol occasionally leads to urinary retention, and also, in some patients excessive sweating may appear.

Clinical efficacy

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

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

In the CATIE study, which evaluated the efficacy of antipsychotic treatments (using AT and AA) in 1,493 patients with schizophrenia, it was shown that these drugs had a rather moderate efficacy in treating this disease. Furthermore, the lack of efficacy or the appearance of side effects caused 74% of the patients to leave the study before it ended.

The study authors concluded that olanzapine (AA) was the most effective antipsychotic of those studied and that there were no differences among the rest (zuclopenthixol is included here). Nevertheless, the greater efficacy of olanzapine was counteracted by an increase in metabolic adverse effects. In any case, the high withdrawal rate shows the limitations of antipsychotics (either AT or AA) in terms of efficacy and safety in the treatment of schizophrenia.

Bibliographic references:

• Arango, C., Bombín, I., González-Salvador, T., García-Cabeza, I., & Bobes, J. (2006). Randomized clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence. European psychiatry, 21 (1), 34-40.
• Bermejo, J. C., & Rodicio, S. G. (2007). Typical antipsychotics. Atypical antipsychotics.
• Jerling, M., Dahl, M. L., Åberg ‐ Wistedt, A., Liljenberg, B., Landell, N. E., Bertilsson, L., & Sjöqvist, F. (1996). The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Clinical Pharmacology & Therapeutics, 59 (4), 423-428.