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 m ...

primarily used to treat

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. It may also be used short term in those with

generalized anxiety disorder Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning. Individuals with GAD are often overly con ...

but is less preferred to

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat co ...

. 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 classi ...

. It was approved for medical use in the United States in 1959.

Medical uses

Schizophrenia

Trifluoperazine is an effective

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

for people with schizophrenia condition. 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 ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

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 d ...

chlorprothixene Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group. Medical uses Chlorprothixene's principal indications are the treatment of psychotic disorders (e.g. schizophrenia) and of acut ...

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 chlorp ...

, 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 The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

pathogens In biology, a pathogen (, "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 germ. The term ...

such as '' Balamuthia'' 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 an iatrogenic disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips, which occurs following treatment with medication. Additional mo ...

, 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 Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...

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

akathisia Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those a ...

dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...

, and

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

. 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 aslee ...

and anticholinergic side effects such as red eye and

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

(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 antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, va ...

. Trifluoperazine can lower the seizure threshold. The

antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

action of trifluoperazine can cause excessive dilation of the pupils (

mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

), which increases the chances of patients with

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

developing

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

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 Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

, and blood dyscrasias. 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 Beta-1 ad ...

, antidopaminergic, and minimal

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

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

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 compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

delusion A delusion is a 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 some other m ...

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 Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

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 hav ...

short-term use. In the past, trifluoperazine was used in fixed combinations with the MAO inhibitor (antidepressant)

tranylcypromine Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used a ...

( tranylcypromine/trifluoperazine) to attenuate the strong stimulating effects of this antidepressant. This combination was sold under the brand name Jatrosom N, Stelapar, Parstelin, among others. It remained available in

Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...

under the brand name Parmodalin (10 mg of tranylcypromine and 1 mg of trifluoperazine) until its discontinuation in 2019. 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 (: neuroses) is a term mainly used today by followers of Psychoanalytic theory, Freudian thinking to describe mental disorders caused by past anxiety, often that has been Repression (psychoanalysis), repressed. In recent history, the ...

and

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

existed under the brand name Jalonac.

References

{{Tricyclics Trifluoromethyl compounds Phenothiazines 4-Methylpiperazin-1-yl compounds Typical antipsychotics