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 medications, typical neuroleptics, was effective in alleviating the positive symptoms of psychosis (such as delusions and hallucinations), but not so effective in alleviating the negative symptoms (anhedonia, avolition or emotional dullness). An example of this group of drugs is zuclopenthixol, which we will talk about throughout the article.
Below 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.
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 medication was introduced to the market in 1978 and is currently available in various presentations, mainly intramuscular injections and tablets.
Several generations of neuroleptic medications have been developed and marketed over the years; The first of them, known as typical antipsychotics, includes zuclopenthixol (from the group of phenothiazines) and other classic neuroleptics such as haloperidol and chlorpromazine.
This first generation of medications for the treatment of psychosis was left behind, being 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, avolition, or emotional dullness).
Currently, zuclopenthixol 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 crises, especially with symptoms of agitation and/or depression. Normally, the most used route of administration is injection, 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 dopamine D1 and D2 receptors, 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 H1 histamine 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 medication, 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).
Contraindications
The consumption of zuclopenthixol is contraindicated in acute poisoning with alcohol, barbiturates and opiates, comatose states, circulatory collapse, hypersensitivity to thioxanthenes, depression of the central nervous system, blood dyscrasias or spinal depression, pheochromocytoma, porphyrias, glaucoma, risk of urinary retention in urethroprostatic people and liver and/or kidney failure.
Patients with cardiovascular disorders should take special caution, since the use of zuclopenthixol can cause hypotension and arrhythmias. In people with respiratory problems or asthma, this medication can produce depressant effects on respiratory function. Epileptic patients should also be cautious, because this drug can lower the seizure threshold, especially in high-risk people.
Side effects
The use of zuclopenthixol It can cause a series of side effects and adverse reactions that must be taken into consideration Among the most worrying are: neuroleptic malignant syndrome, which is characterized by psychological alterations, muscle 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.
Let’s see below what are the main organic and psychiatric alterations associated with the consumption of zuclopenthixol.
Neurological disorders
Frequently (more than 10%), there may be tremors, muscle rigidity, parkinsonism, akathisia, dystonia and dizziness. Occasionally (less than 10%) paresthesia, dyskinesia, tardive dyskinesia and headache may occur.
Psychological/psychiatric alterations
Frequently, the use of zuclopenthixol can lead to sleep disorders, 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
The consumption of zuclopenthixol may 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 in addition, excessive sweating may appear in some patients.
Clinical efficacy
As we mentioned at the beginning, zuclopenthixol belongs to the group of typical antipsychotics, the first generation of drugs used to treat 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 considerably reduced
In a review of several studies that compared the clinical efficacy of typical antipsychotics (AT) versus atypical or second-generation antipsychotics (AA), it was found that AA were not superior to AT in efficacy or tolerability. In another meta-analysis it was observed that TAs used in optimal doses did not have a higher risk of causing extrapyramidal symptoms than AAs, although lower efficacy was observed.
In the CATIE study, which evaluated the effectiveness of antipsychotic treatments (using AT and AA) in 1,493 patients with schizophrenia, it was shown that these medications had a rather moderate effectiveness in treating this disease. Furthermore, lack of efficacy or the appearance of side effects caused 74% of patients to abandon the study before it ended.
The authors of the study concluded that olanzapine (AA) was the most effective antipsychotic of those studied and that there were no differences among the rest (this includes zuclopenthixol). Nevertheless, the greater efficacy of olanzapine was offset by an increase in metabolic adverse effects In any case, such a high withdrawal rate highlights the limitations of antipsychotics (whether AT or AA) in terms of efficacy and safety in the treatment of schizophrenia.
