Fluanxol (Flupentixol)
Thioxanthene neuroleptic in daily dose and depot injection
Fluanxol is the brand name of the Danish pharmaceutical company Lundbeck for flupentixol, a neuroleptic from the thioxanthene class. The substance was developed in the 1960s and has since been firmly established in psychiatry. In Germany tablets of 0.5, 1 and 5 mg and depot preparations (Fluanxol Depot, flupentixol decanoate) are available. Generics exist. Flupentixol can be used in two dose ranges with distinct effect profiles.
At low dose, flupentixol acts mainly as an activating and anxiolytic drug; at higher dose it is antipsychotic. This feature makes it interesting in the treatment of mild to moderate depression with reduced drive and in anxiety syndromes, while higher doses are used in schizophrenia and other psychotic disorders. The depot form allows dosing every 2 to 4 weeks and is advantageous when adherence is a concern.
Mechanism of Action
Flupentixol mainly blocks postsynaptic dopamine D2 receptors and, to a lesser extent, D1 receptors. It also antagonises serotonin 5-HT2A receptors, α1 adrenoceptors and, moderately, histamine H1 receptors. The muscarinic component is weaker than that of classic phenothiazines such as chlorpromazine.
The receptor profile explains the dual effect. At low dose the blockade of presynaptic dopamine autoreceptors dominates, paradoxically enhancing dopaminergic neurotransmission and producing a drive increasing action. At higher dose the postsynaptic receptor blockade dominates, producing antipsychotic and sedative effects. The crossover point is around 3 mg per day.
As a depot form, flupentixol decanoate is injected intramuscularly and released slowly over 2 to 4 weeks. Oral bioavailability is about 40 percent and the half life of the oral form is 35 hours. Depot injection produces a stable drug level over several weeks.
Indications
- Schizophrenia and schizoaffective disorders in acute and maintenance therapy, particularly with productive psychotic symptoms and limited cooperation (depot form)
- Mild to moderate depression with reduced drive at low dose (0.5 to 1 mg in the morning)
- Anxiety syndromes, asthenic states at low dose
- Chronic paranoid psychoses as maintenance therapy
- Adherence problems in schizophrenia as Fluanxol Depot every 2 to 4 weeks intramuscularly
Dosage and Administration
Depression, anxiety: 0.5 to 3 mg orally in the morning, not after 4 pm because of sleep disturbance. Acute psychosis: oral 3 to 40 mg per day in 2 to 3 divided doses, in exceptional cases up to 60 mg. Start with a low dose and titrate weekly until effect.
Fluanxol Depot (flupentixol decanoate): intramuscular injection into the gluteal muscle, 20 to 40 mg every 2 to 4 weeks, in individual cases up to 100 mg every 2 weeks. The switch from oral to depot form takes account of cumulative oral daily dose. Oral bridging is often needed during the first weeks after the first depot injection.
Renal impairment: no formal dose adjustment, caution in severe impairment because of accumulation risk. Hepatic impairment: dose reduction in moderate to severe impairment because of reduced metabolism by CYP enzymes. Older patients: lower doses, slower titration, consider increased fall and delirium risk.
Side Effects
Common: extrapyramidal motor disorders (parkinsonism, akathisia, early dyskinesia), sedation (stronger at higher doses), dry mouth, constipation, blurred vision, orthostasis, weight gain, rise in prolactin with cycle disturbances, galactorrhoea or erectile dysfunction.
Uncommon: tachycardia, elevated liver enzymes, rash, increased skin reaction potential under sun, headache, sleep disturbances.
Serious: neuroleptic malignant syndrome (fever, rigidity, impaired consciousness), tardive dyskinesia with long term use, QT prolongation with risk of torsade de pointes, agranulocytosis, seizures from a lowered seizure threshold, venous thromboembolism.
Dementia patients: in older patients with dementia the risk of cerebrovascular events and overall mortality is increased; the indication must be particularly strict in this group.
Interactions
- Central depressants (alcohol, benzodiazepines, opioids): enhanced sedation, respiratory depression
- QT prolonging drugs (amiodarone, sotalol, macrolides, ondansetron, methadone): additive torsade de pointes risk, ECG monitoring required
- Levodopa, dopamine agonists: mutual reduction of effect
- Anticholinergics (biperiden, tricyclic antidepressants): additive anticholinergic side effects
- Lithium: occasional neurotoxicity, close monitoring
- Antihypertensives: enhanced hypotension
- CYP2D6 and CYP3A4 inhibitors: flupentixol plasma levels may rise
Special Notes
Contraindications: comatose states, acute intoxication with central depressants, circulatory collapse, pheochromocytoma, leukopenia or other bone marrow damage, narrow angle glaucoma, known QT prolongation, Parkinson's disease (relative).
Low dose for depression: flupentixol 0.5 to 3 mg can act as an activating agent and was often used in mild depressive states and anxiety in the past. This indication is debated today because better alternatives (SSRIs, SNRIs, psychotherapy) exist. In older patients and in anxiety indications, however, there is a long clinical tradition.
Pregnancy: use only on a compelling indication; neonates exposed in the third trimester may show withdrawal or extrapyramidal symptoms. Breastfeeding: passage into breast milk, breastfeeding during therapy is not recommended.
Monitoring: ECG with QTc before and during therapy, blood count, liver, renal and metabolic parameters, prolactin when endocrine side effects are suspected. Evaluate fall risk in older patients; smokers may have lower plasma levels because of CYP1A2 induction.
You might also be interested in
- Chlorprothixene, related sedating thioxanthene
- Chlorpromazine, historical first generation phenothiazine
- Aripiprazole, modern atypical antipsychotic with partial dopamine agonist activity
- Levomepromazine, phenothiazine in palliative care
- Prothipendyl, low potency neuroleptic for agitation
Frequently Asked Questions
Does Fluanxol act differently depending on the dose?
Yes. At doses up to about 3 mg, blockade of presynaptic dopamine autoreceptors predominates, producing an activating and slightly mood lifting effect. At higher doses the postsynaptic receptor blockade dominates, producing antipsychotic effect and sedation. This dual profile is a distinctive feature of the drug.
What is the depot form used for?
Fluanxol Depot is injected intramuscularly and released over 2 to 4 weeks. The depot form simplifies maintenance therapy in chronic schizophrenia, especially when daily tablet intake is inconsistent. Relapse rates fall significantly and adherence becomes verifiable.
Why must I not take the tablet in the evening?
Low dose flupentixol is more activating and may cause sleep disturbance if taken in the evening. The usual recommendation is to take it in the morning or at lunchtime, no later than 4 pm. At higher antipsychotic doses splitting the dose between morning and midday is sensible.
What is tardive dyskinesia?
Tardive dyskinesia consists of involuntary movement disorders that can develop after months or years of neuroleptic therapy. Typical features are tongue movements, lip smacking, grimacing and limb movements. The rate under flupentixol in clinical studies is about 3 to 5 percent per year and is lower under atypical antipsychotics.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guideline on Schizophrenia and Psychopharmacotherapy
- Gelbe Liste, Flupentixol active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
Legal Notice and Disclaimer
The information provided on this page is for general informational purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace consultation with a licensed physician or pharmacist. Medicines should only be taken on medical prescription or via a pharmacy. All information is based on product information and recognised scientific sources published at the time of creation; the manufacturer's current summary of product characteristics is always authoritative. Sanoliste assumes no liability for the completeness, timeliness or accuracy of the information presented. In a medical emergency, call the emergency number 112 (Europe).