Trifluoperazine

Trifluoperazine
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a682121
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration		 oral, IM
ATC code N05AB06 (WHO)
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 10–20 hours
Identifiers
CAS Number 117-89-5 YesY
PubChem (CID) 5566
IUPHAR/BPS 214
DrugBank DB00831 YesY
ChemSpider 5365 YesY
UNII 214IZI85K3 YesY
ChEBI CHEBI:45951 YesY
ChEMBL CHEMBL422 YesY
PDB ligand ID TFP (PDBe, RCSB PDB)
ECHA InfoCard 100.003.837
Chemical and physical data
Formula C21H24F3N3S
Molar mass 407.497 g/mol
3D model (Jmol) Interactive image
  (verify)

Trifluoperazine (Eskazinyl, Eskazine, Jatroneural, Modalina, Stelazine, Terfluzine, Trifluoperaz, Triftazin) is a typical antipsychotic of the phenothiazine chemical class.

Uses

The primary application of trifluoperazine is for schizophrenia. Other official indications may vary country by country, but generally it is also indicated for use in agitation and patients with behavioural problems, severe nausea and vomiting as well as severe anxiety. Trials have shown a moderate benefit of this drug in patients with borderline personality disorder.[1] Its use in many parts of the world has declined because of highly frequent and severe early and late tardive dyskinesia, a type of extrapyramidal symptom. The annual development rate of tardive dyskinesia may be as high as 4%.

A 2005 study of patients with generalized anxiety disorder [2] noted that:

“ The results of a randomized placebo-controlled, flexible-dose acute treatment study indicate that the antipsychotic drug trifluoperazine had superior efficacy from the first week of double-blind treatment, although there were markedly more treatment emergent adverse events with trifluoperazine (62%,compared to 46% with placebo) ”

A 2006 study suggested that trifluoperazine may be able to reverse addiction to opioids.[3]

A multi-year UK study by the Alzheimer's Research Trust suggested that this and other antipsychotic drugs commonly given to patients with Alzheimer's disease with mild behavioural problems often make their condition worse.[4] The study concluded that

“ For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status and by some measures improved functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this possibility must be weighed against the unwanted effects of therapy. The current study helps to inform a clinical management strategy for current practice, but the considerable risks of maintenance therapy highlight the urgency of further work to find, develop, and implement safer and more effective treatment approaches for neuropsychiatric symptoms in people with AD. ”

Pharmacology

Trifluoperazine has central antiadrenergic,[5] antidopaminergic,[6][7] and minimal anticholinergic effects.[8] It is believed to work by blockading dopamine D1 and D2 receptors in the mesocortical and mesolimbic pathways, relieving or minimizing such symptoms of schizophrenia as hallucinations, delusions, and disorganized thought and speech.[9]

Effects

Comparison of trifluoperazine to placebo [10]
Measured outcome Findings in words Findings in numbers Quality of evidence
Global effects
Clinical improvement at 19 weeks 4.5 times more likely to have a clinical significant response with trifluoperazine RR 4.61 CI 1.54 to 13.84 Low
Relapse or worsening at 5 months 65% less likely to have relapse or worsening of symptoms with trifluoperazine RR 0.34 CI 0.23 to 0.49
Significant response in psychotic symptoms No more likely to experience ‘intensified psychotic symptoms’ with trifluoperazine RR 1.05 CI 0.54 to 2.05 Very Low
Adverse effects
Severe adverse effects at 2 months 30% more likely to experience severe adverse effects with trifluoperazine RR 1.31 CI 0.22 to 7.80 Very low
Agitation or distress Twice more likely to experience clinically significant agitation or distress with trifluoperazine RR 2.00 CI 0.19 to 20.72

Side effects

A 2004 meta-analysis of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as akathisia, dystonia, and Parkinsonism.[9] It is also more likely to cause somnolence and anticholinergic side effects such as red eye and xerostomia (dry mouth).[9] All antipsychotics can cause the rare and sometimes fatal neuroleptic malignant syndrome.[11] Trifluoperazine can lower the seizure threshold.[12] The antimuscarinic action of trifluoperazine can cause excessive dilation of the pupils (mydriasis), which increases the chances of patients with hyperopia developing glaucoma.[13]

Contraindications

Trifluoperazine is contraindicated in CNS depression, coma, and blood dyscrasias. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment.

Formulations

In the United Kingdom and some other countries, trifluoperazine is sold and marketed under the brand 'Stelazine'.

The drug is sold as tablet, liquid and 'Trifluoperazine-injectable USP' for deep intramuscular short-term use.

In the past, trifluoperazine was used in fixed combinations with the MAO inhibitor (antidepressant) tranylcypromine (tranylcypromine/trifluoperazine) to attenuate the strong stimulating effects of this antidepressant. This combination was sold under the brand name Jatrosom N. Likewise a combination with amobarbital (potent sedative/hypnotic agent) for the amelioration of psychoneurosis and insomnia existed under the brand name Jalonac. In Italy the first combination is still available, sold under the brand name Parmodalin (10 mg of tranylcypromine and 1 mg of trifluoperazine).

References

  1. ↑ Rex William Cowdry; David L. Gardner (1988). "Pharmacotherapy of Borderline Personality DisorderAlprazolam, Carbamazepine, Trifluoperazine, and Tranylcypromine". Arch Gen Psychiatry. 45 (2): 111–119. doi:10.1001/archpsyc.1988.01800260015002.
  2. ↑ David S. Baldwin, Polkinghorn (2005). "Evidence-based pharmacotherapy of generalized anxiety disorder". International Journal of Neuropsychopharmacology. 8: 293–302. doi:10.1017/S1461145704004870.
  3. ↑ Tang L, Shukla PK, Wang ZJ (2006). "Trifluoperazine, an orally available clinically used drug, disrupts opioid antinociceptive tolerance". Neuroscience Letters. 397 (1–2): 1–4. doi:10.1016/j.neulet.2005.11.050. PMID 16380209. Lay summary – ScienceDaily (2006-02-13).
  4. ↑ Ballard C, Lana MM, Theodoulou M, et al. (April 2008). Brayne C, ed. "A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)". PLoS Medicine. 5 (4): e76. doi:10.1371/journal.pmed.0050076. PMC 2276521Freely accessible. PMID 18384230. Lay summary – BBC News (2008-04-01). Neuroleptics provided no benefit for patients with mild behavioural problems, but were associated with a marked deterioration in verbal skills
  5. ↑ Huerta-Bahena J, Villalobos-Molina R, García-Sáinz JA (January 1983). "Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects". Molecular Pharmacology. 23 (1): 67–70. PMID 6135146. Retrieved 2009-06-21.
  6. ↑ Seeman P, Lee T, Chau-Wong M, Wong K (June 1976). "Antipsychotic drug doses and neuroleptic/dopamine receptors". Nature. 261 (5562): 717–9. Bibcode:1976Natur.261..717S. doi:10.1038/261717a0. PMID 945467.
  7. ↑ Creese I, Burt DR, Snyder SH (1996). "Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs". The Journal of Neuropsychiatry and Clinical Neurosciences. 8 (2): 223–6. PMID 9081563. Retrieved 2009-06-21.
  8. ↑ Ebadi, Manuchair S (1998). "Trifluoperazine Hydrochloride". CRC desk reference of clinical pharmacology (illustrated ed.). CRC Press. ISBN 978-0-8493-9683-0. Retrieved 2009-06-21.
  9. 1 2 3 Marques LO, Lima MS, Soares BG (2004). Marques, Luciana de Oliveira, ed. "Trifluoperazine for schizophrenia". Cochrane Database of Systematic Reviews (1): CD003545. doi:10.1002/14651858.CD003545.pub2. PMID 14974020.
  10. ↑ Koch K, Mansi K, Haynes E, Adams CE, Sampson S, Furtado VA (2014). "Trifluoperazine versus placebo for schizophrenia". Cochrane Database of Systematic Reviews (1) doi: 10.1002/14651858.CD010226.pub2. Retrieved 19 November 2014.
  11. ↑ Smego RA, Durack DT (June 1982). "The neuroleptic malignant syndrome". Archives of Internal Medicine. 142 (6): 1183–5. doi:10.1001/archinte.142.6.1183. PMID 6124221.
  12. ↑ Hedges D, Jeppson K, Whitehead P (July 2003). "Antipsychotic medication and seizures: a review". Drugs of Today (Barcelona, Spain : 1998). 39 (7): 551–7. doi:10.1358/dot.2003.39.7.799445. PMID 12973403.
  13. ↑ Boet DJ (July 1970). "Toxic effects of phenothiazines on the eye". Documenta Ophthalmologica. Advances in Ophthalmology. 28 (1): 1–69. doi:10.1007/BF00153873. PMID 5312274.
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