Zuclopenthixol (brand names Cisordinol, Clopixol and others), also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol (Sordinol, Ciatyl).
Zuclopenthixol is a D1 and D2 antagonist, α1-adrenergic and 5-HT2 antagonist.
Medical uses
Available forms
Zuclopenthixol is available in three major
drug form:
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As zuclopenthixol decanoate ( Clopixol Depot, Cisordinol Depot), it is a long-acting intramuscular injection. Its main use is as a long-acting injection given every two or three weeks to people with schizophrenia who have a poor compliance with medication and suffer frequent relapses of illness.
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As zuclopenthixol acetate ( Clopixol-Acuphase, Cisordinol-Acutard), it is a shorter-acting intramuscular injection used in the acute sedation of psychotic inpatients. The effect peaks at 48–72 hours providing 2–3 days of sedation.
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As zuclopenthixol dihydrochloride ( Clopixol, Cisordinol), it is a tablet used in the treatment of schizophrenia in those who are compliant with oral medication.
It is also used in the treatment of acute bipolar mania.
Dosing
As a long-acting injection, zuclopenthixol decanoate comes in a 200 mg and 500 mg ampoule. Doses can vary from 50 mg weekly to the maximum licensed dose of 600 mg weekly. In general, the lowest effective dose to prevent relapse is preferred. The interval may be shorter as a patient starts on the medication before extending to 3 weekly intervals subsequently. The dose should be reviewed and reduced if side effects occur, though in the short-term an anticholinergic medication
benztropine may be helpful for tremor and stiffness, while
diazepam may be helpful for akathisia. 100 mg of zuclopenthixol decanoate is roughly equivalent to 20 mg of flupentixol decanoate or 12.5 mg of
fluphenazine decanoate.
In oral form zuclopenthixol is available in 2, 10, 25 and 40 mg tablets, with a dose range of 20–60 mg daily.
Side effects
Chronic administration of zuclopenthixol (30 mg/kg/day for two years) in rats resulted in small, but significant, increases in the incidence of thyroid parafollicular carcinomas and, in females, of mammary adenocarcinomas and of pancreatic islet cell adenomas and carcinomas. An increase in the incidence of mammary adenocarcinomas is a common finding for D
2 antagonists which increase prolactin secretion when administered to rats. An increase in the incidence of pancreatic islet cell tumours has been observed for some other D
2 antagonists. The physiological differences between rats and humans with regard to prolactin make the clinical significance of these findings unclear.
Drug withdrawal: Abrupt cessation of therapy may cause acute withdrawal symptoms (eg, nausea, vomiting, or insomnia). Symptoms usually begin in 1 to 4 days of withdrawal and subside within 1 to 2 weeks.
Other permanent side effects are similar to many other typical antipsychotics, namely extrapyramidal symptoms as a result of dopamine blockade in subcortical areas of the brain. This may result in symptoms similar to those seen in Parkinson's disease and include a restlessness and inability to sit still known as akathisia, a slow tremor and stiffness of the limbs.
Zuclopenthixol decanoate induces a transient dose-dependent sedation. However, if the patient is switched to maintenance treatment with zuclopenthixol decanoate from oral zuclopenthixol or from i.m. zuclopenthixol acetate the sedation will be no problem. Tolerance to the unspecific sedative effect develops rapidly.
- Very common Adverse Effects (≥10% incidence)
- Common (1–10%)
- Uncommon (0.1–1%)
- Rare (0.01–0.1%)
- Very rare (<0.01%)
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Cholestatic hepatitis
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Jaundice
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Neuroleptic malignant syndrome
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Venous thromboembolism
Pharmacology
Pharmacodynamics
Zuclopenthixol antagonises both dopamine D
1 and D
2 receptors, α
1-adrenoceptors and 5-HT
2 receptors with a high affinity, but has no affinity for muscarinic acetylcholine receptors. It weakly antagonises the histamine (H
1) receptor but has no α
2-adrenoceptor blocking activity .
Evidence from in vitro work and clinical sources (i.e. therapeutic drug monitoring databases) suggests that both CYP2D6 and CYP3A4 play important roles in zuclopenthixol metabolism.
Pharmacokinetics
History
Zuclopenthixol was introduced by Lundbeck in 1978.
