Trifluoperazine, marketed under the brand name Stelazine among others, is a

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...

primarily used to treat

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

. It may also be used short term in those with

generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...

but is less preferred to

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

. It is of the phenothiazine

chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classificati ...

Medical uses

Schizophrenia

Trifluoperazine is an effective

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

for people with schizophrenia. There is low-quality evidence that trifluoperazine increases the chance of being improved when compared to placebo when people are followed up for 19 weeks. There is low-quality evidence that trifluoperazine reduces the risk of relapse when compared with placebo when people are followed for 5 months. As of 2014 there was no good evidence for a difference between trifluoperazine and

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

with respect to the risk of experiencing intensified symptoms over a 16-week period nor in reducing significant agitation or distress. There is no good evidence that trifluoperazine is more effective for schizophrenia than lower-potency antipsychotics like

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

, chlorprothixene,

thioridazine Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwid ...

and

levomepromazine Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic drug. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. It is a low-potency antipsychotic (approximately half as potent as chlorpr ...

, but trifluoperazine appears to cause more adverse effects than these drugs.

Other

It appears to be effective for people with

but the benefitrisk ratio was unclear as of 2005. It has been experimentally used as a drug to kill

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...

in humans.

Side effects

Its use in many parts of the world has declined because of highly frequent and severe early and late

tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

, a type of

extrapyramidal symptom Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

. The annual development rate of tardive dyskinesia may be as high as 4%. A 2004

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...

of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

dystonia Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often int ...

, and

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lew ...

. It is also more likely to cause

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

and anticholinergic side effects such as red eye and

xerostomia Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

(dry mouth). All antipsychotics can cause the rare and sometimes fatal

neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fa ...

. Trifluoperazine can lower the seizure threshold. The

antimuscarinic A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of th ...

action of trifluoperazine can cause excessive dilation of the pupils (

mydriasis Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, a ...

), which increases the chances of patients with

hyperopia Far-sightedness, also known as long-sightedness, hypermetropia, or hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blurred effect is due to incoming light being focused behind, i ...

developing

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...

Contraindications

Trifluoperazine is contraindicated in CNS depression,

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

, and

blood dyscrasia In medicine, both ancient and modern, a dyscrasia is any of various disorders. The word has ancient Greek roots meaning "bad mixture". The concept of dyscrasia was developed by the Greek physician Galen (129–216 AD), who elaborated a model of h ...

s. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment.

Mechanism of action

Trifluoperazine has central

antiadrenergic An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2 ...

, antidopaminergic, and minimal

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

effects. It is believed to work by blockading dopamine D₁ and D₂ receptors in the

mesocortical The mesocortical pathway is a dopaminergic pathway that connects the ventral tegmentum to the prefrontal cortex. It is one of the four major dopamine pathways in the brain. It is essential to the normal cognitive function of the dorsolateral pr ...

and

mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ven ...

s, relieving or minimizing such symptoms of schizophrenia as

hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...

delusion A delusion is a false fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or som ...

s, and disorganized thought and speech. It also has antihistaminergic properties ( H₁ K_i = 17.5).

Names

Brand names include Eskazinyl, Eskazine, Jatroneural, Modalina, Sizonil, Stelazine, Stilizan, Terfluzine, Trifluoperaz and Triftazin. In the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and ...

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 Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles ha ...

short-term use. GP studying pharmacological data has indicated cases of neck vertebrae irreversible fusing leading to NHS preparations being predominantly of the liquid form trifluoperazine as opposed to the tablet form as in Stela zine etc. In the past, trifluoperazine was used in fixed combinations with the

MAO inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...

(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 Amobarbital (formerly known as amylobarbitone or sodium amytal as the soluble sodium salt) is a drug that is a barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a slightly bitter taste. ...

(potent sedative/hypnotic agent) for the amelioration of

psychoneurosis Neurosis is a class of functional mental disorders involving chronic distress, but neither delusions nor hallucinations. The term is no longer used by the professional psychiatric community in the United States, having been eliminated from th ...

and

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

existed under the brand name Jalonac. In

Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical ...

the first combination is still available, sold under the brand name Parmodalin (10 mg of tranylcypromine and 1 mg of trifluoperazine).

References

{{Tricyclics Trifluoromethyl compounds Phenothiazines Piperazines Typical antipsychotics