Flupentixol
Flupentixol, also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol.
Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.
Medical uses
Flupentixol's main use is as a long-acting injection given once in every two or three weeks to individuals with schizophrenia who have poor compliance with medication and have frequent relapses of illness, though it is also commonly given as a tablet. There is little formal evidence to support its use for this indication but it has been in use for over fifty years.Flupentixol is also used in low doses as an antidepressant. There is tentative evidence that it reduces the rate of deliberate self-harm, among those who self-harm repeatedly.
Adverse effects
Adverse effect incidence;Common adverse effects include:
- Extrapyramidal side effects such as:
- * Muscle rigidity
- * Hypokinesia
- * Hyperkinesia
- * Parkinsonism
- * Tremor
- * Akathisia
- * Dystonia
- Dry mouth
- Constipation
- Hypersalivation – excessive salivation
- Blurred vision
- Diaphoresis – excessive sweating
- Nausea
- Dizziness
- Somnolence
- Restlessness
- Insomnia
- Overactivity
- Headache
- Nervousness
- Fatigue
- Myalgia
- Hyperprolactinemia and its complications such as:
- * Sexual dysfunction
- * Amenorrhea – cessation of menstrual cycles
- * Gynecomastia – enlargement of breast tissue in males
- * Galactorrhea – the expulsion of breast milk that's not related to breastfeeding or pregnancy
- Dyspepsia – indigestion
- Abdominal pain
- Flatulence
- Nasal congestion
- Polyuria – passing more urine than usual
- Fainting
- Palpitations
- Blood dyscrasias, such as:
- * Agranulocytosis – a drop in white blood cell counts that leaves one open to potentially life-threatening infections
- * Neutropenia – a drop in the number of neutrophils in one's blood
- * Leucopenia – a less severe drop in white blood cell counts than agranulocytosis
- * Thrombocytopenia – a drop in the number of platelets in the blood. Platelets are responsible for blood clotting and hence this leads to an increased risk of bruising and other bleeds
- Neuroleptic malignant syndrome – a potentially fatal condition that appear to result from central D2 receptor blockade. The symptoms include:
- * Hyperthermia
- * Muscle rigidity
- * Rhabdomyolysis
- * Autonomic instability
- * Mental status changes
- Jaundice
- Abnormal liver function test results
- Tardive dyskinesia – an often incurable movement disorder that usually results from years of continuous treatment with antipsychotic drugs, especially typical antipsychotics like flupenthixol. It presents with repetitive, involuntary, purposeless and slow movements; TD can be triggered by a fast dose reduction in any antipsychotic.
- Hypotension
- Confusional state
- Seizures
- Mania
- Hypomania
- Depression
- Hot flush
- Anergia
- Appetite changes
- Weight changes
- Hyperglycemia – high blood glucose levels
- Abnormal glucose tolerance
- Pruritus – itchiness
- Rash
- Dermatitis
- Photosensitivity – sensitivity to light
- Oculogyric crisis
- Accommodation disorder
- Sleep disorder
- Impaired concentration
- Tachycardia
- QTc interval prolongation – an abnormality in the electrical activity of the heart that can lead to potentially fatal changes in heart rhythm
- Torsades de pointes
- Miosis – constriction of the pupil of the eye
- Paralytic ileus – paralysis of the bowel muscles leading to severe constipation, inability to pass wind, etc.
- Mydriasis
- Glaucoma
Interactions
Contraindications
It should not be given in the following disease states:- Pheochromocytoma
- Prolactin-dependent tumors such as pituitary prolactinomas and breast cancer
- Long QT syndrome
- Coma
- Circulatory collapse
- Subcortical brain damage
- Blood dyscrasia
- Parkinson's disease
- Dementia with Lewy bodies
Pharmacology
Pharmacodynamics
Binding profile| Protein | cis-flupentixol | trans-flupentixol |
| 5-HT1A | 8028 | — |
| 5-HT2A | 87.5 | — |
| 5-HT2C | 102.2 | — |
| mAChRs | Neg. | Neg. |
| D1 | 3.5 | 474 |
| D2 | 0.35 | 120 |
| D3 | 1.75 | 162.5 |
| D4 | 66.3 | >1000 |
| H1 | 0.86 | 5.73 |
Acronyms used:
HFC – Human frontal cortex receptor
MB – Mouse brain receptor
RC – Cloned rat receptor
A study measuring the in vivo receptor occupancies of 13 schizophrenic patients treated with 5.7 ± 1.4 mg/day of flupentixol found 50-70% receptor occupancy for D2, 20 ± 5% for D1, and 20 ± 10% for 5-HT2A.
Its antipsychotic effects are predominantly a function of D2 antagonism.
Its antidepressant effects at lower doses are not well understood; however, it may be mediated by functional selectivity and/or preferentially binding to D2 autoreceptors at low doses, resulting in increased postsynaptic activation via higher dopamine levels. Flupentixol's demonstrated ability to raise dopamine levels in mice and flies lends credibility to the supposition of autoreceptor bias. Functional selectivity may be responsible through causing preferential autoreceptor binding or other means. The effective dosage guideline for an antipsychotic is very closely related to its receptor residency time and long receptor residency time is strongly correlated with likehood of pronounced functional selectivity; thus, with a maximum guideline dose of only 18 mg/day for schizophrenia, there is a significant possibility of this drug possessing unique signalling characteristics that permit counterintuitive dopaminergic action at low doses.
Flupentixol also inhibits tubulin polymerization.