Trifluoperazine

Trifluoperazine

Systematic (IUPAC) name
10-[3-(4-methylpiperazin-1-yl)propyl]- 2-(trifluoromethyl)-10H-phenothiazine
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682121
Pregnancy category	AU: C US: C (Risk not ruled out)
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	oral, IM
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	10–20 hours
Identifiers
CAS Number	117-89-5 Y
ATC code	N05AB06 (WHO)
PubChem	CID: 5566
IUPHAR/BPS	214
DrugBank	DB00831 Y
ChemSpider	5365 Y
UNII	214IZI85K3 Y
ChEBI	CHEBI:45951 Y
ChEMBL	CHEMBL422 Y
PDB ligand ID	TFP (PDBe, RCSB PDB)
Chemical data
Formula	C21H24F3N3S
Molecular mass	407.497 g/mol
SMILES FC(F)(F)c2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(C)CC4
InChI InChI=1S/C21H24F3N3S/c1-25-11-13-26(14-12-25)9-4-10-27-17-5-2-3-6-19(17)28-20-8-7-16(15-18(20)27)21(22,23)24/h2-3,5-8,15H,4,9-14H2,1H3 Y Key:ZEWQUBUPAILYHI-UHFFFAOYSA-N Y
(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. 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 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.

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. 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, antidopaminergic, and minimal anticholinergic effects. 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.

Effects

Comparison of trifluoperazine to placebo

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. It is also more likely to cause somnolence and anticholinergic side effects such as red eye and xerostomia (dry mouth). All antipsychotics can cause the rare and sometimes fatal neuroleptic malignant syndrome. Trifluoperazine can lower the seizure threshold. The antimuscarinic action of trifluoperazine can cause excessive dilation of the pupils (mydriasis), which increases the chances of patients with hyperopia developing glaucoma.

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).