Trifluoperazine (Stelazine) is a phenothiazine antipsychotic drug that is used to treat patients with schizophrenia. It is occasionally used to treat anxiety disorder but is generally not a preferred drug for that.

Trifluoperazine Uses:

• Nonpsychotic anxiety:

  • Used for short-term treatment of generalized nonpsychotic anxiety.

• Schizophrenia:

  • Management of schizophrenia.

• Off Label Use of Trifluoperazine in Adults:

  • Psychosis/agitation associated with dementia

Read: Aducanumab-avwa (Aduhelm Injection for Alzheimer's disease

Trifluoperazine (Stelazine) Dose in Adults

Trifluoperazine (Stelazine) Dose in the treatment of Nonpsychotic anxiety:

• Oral: 1 or 2 mg two times a day; dose should be titrated gradually based on response and tolerability; maximum: 6 mg per 24 hours; when treating anxiety, the therapy should not exceed 12 weeks; to avoid tardive dyskinesia the dose should not exceed 6 mg per 24 hours for longer than 12 weeks when treating anxiety.

Trifluoperazine (Stelazine) Dose in the treatment of Schizophrenia:

• Oral: Initial: 2 to 5 mg two times a day; dose should be titrated gradually based on response and tolerability
• The usual dosage is 15 or 20 mg per 24 hours in divided doses. Although dose up to 50mg per 24 hours may be required in some patients.

• Discontinuation of therapy:

  • American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines have recommended to slowly taper antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse; antipsychotics with high anti-cholinergic or dopaminergic activity impose the highest risk of withdrawal symptoms.
  • According to the CPA guidelines, the dose should be gradually tapered over 6 to 24 months when discontinuing antipsychotic therapy in patients with schizophrenia, and according to the APA guidelines, the dose should be reduced by 10% each month.
  • The withdrawal symptoms may be prevented by continuing anti-parkinsonism agents for a brief period after discontinuation.
  • The antipsychotics should be switched according to the following 3 strategies:
    1. cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic)
    2. Overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic)
    3. Abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose)
  • Limited evidence is available that suggests ideal switch strategies and taper rates.

Trifluoperazine (Stelazine) Dose in Childrens

Trifluoperazine (Stelazine) Dose in the treatment of Schizophrenia:

Note: The newer agents have replaced its use. Adjust dosage for each individual; the lowest effective dose should be used for the shortest effective duration & the need for continued treatment should be periodically reassessed

• Children 6 to 12 years:

  • Hospitalized or well-supervised patients: Initial: Oral: 1 mg once or twice daily; dose should be gradually titrated according to tolerability. Daily maintenance range: 1 to 15 mg per 24 hours once or twice daily; usual maximum daily dose: 15 mg per 24 hours; higher doses may be required in older children with severe symptoms.

• Adolescent:

  • Initial: 2 to 5 mg two times a day; the dose should be titrated gradually according to tolerability; usual maintenance dose range: 15 to 20 mg per 24 hours in 2 divided doses; maximum daily dose: 40 mg per 24 hours; in small for age patients, the initial doses at the lower end of the range should be considered

• Discontinuation of therapy:

  • Children and Adolescents:

    • American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), National Institute for Health and Care Excellence (NICE), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines have recommended to slowly taper antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse; antipsychotics with high anti-cholinergic or dopaminergic activity impose the highest risk of withdrawal symptoms.
    • The CPA guidelines have recommended that the dose should be gradually tapered over 6 to 24 months when discontinuing antipsychotic therapy in patients with schizophrenia, and according to the APA guidelines, the dose should be reduced by 10% each month.
    • The withdrawal symptoms may be prevented by continuing anti-parkinsonism agents for a brief period after discontinuation.
    • The antipsychotics should be switched according to the following 3 strategies:
      1. cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic)
      2. Overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic)
      3. Abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose)
    • Limited evidence is available that suggests ideal switch strategies and taper rates.

Pregnancy Risk Category: C

• Studies on animal reproduction have not shown adverse effects, except for maternally toxic doses.
• Phenothiazines can cause maternal jaundice, extrapyramidal signs or hyporeflexia in newborn infants.
• Use of antipsychotics in the last trimester may cause withdrawal symptoms in newborns after delivery.
• The newborn might experience agitation, feeding disorders, hypotonia and hypertonia as well as respiratory distress, somnolence and tremor.
• These symptoms may be self-limiting, or may require hospitalization.

Use of trifluoperazine while breastfeeding

• Trifluoperazine secretes in breast milk. It was measured in three infants' serums.
• Milk may contain higher concentrations than the maternal serum.
• Monitor infants for signs of adverse events.
• The manufacturer recommends that the mother discontinue nursing the infant or stop using the drug because of the potential for serious adverse reactions.

Dose in Kidney Disease:

No dosage adjustments provided in the manufacturer’s labeling.

Dose in Liver disease:

No dosage adjustments provided in the manufacturer’s labeling Liver disease is a contraindication for use.

Side effects of Trifluoperazine (Stelazine):

• Cardiovascular:

  • Hypotension
  • Orthostatic Hypotension

• Central Nervous System:

  • Decreased Seizure Threshold
  • Dizziness
  • Disruption Of Body Temperature Regulation
  • Extrapyramidal Reaction (Akathisia, Dystonia, Parkinsonian-Like Syndrome, Tardive Dyskinesia)
  • Headache
  • Neuroleptic Malignant Syndrome (NMS)

• Dermatologic:

  • Skin Discoloration (Blue-Gray)
  • Skin Photosensitivity (Includes Increased Sensitivity To Sun)
  • Skin Rash

• Endocrine & Metabolic:

  • Change In Libido
  • Change In Menstrual Flow
  • Galactorrhea
  • Gynecomastia
  • Hyperglycemia
  • Hypoglycemia
  • Weight Gain

• Gastrointestinal:

  • Constipation
  • Nausea
  • Stomach Pain
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Difficulty In Micturition
  • Ejaculatory Disorder
  • Lactation
  • Mastalgia
  • Priapism
  • Urinary Retention

• Hematologic & Oncologic:

  • Agranulocytosis
  • Aplastic Anemia
  • Eosinophilia
  • Hemolytic Anemia
  • Immune Thrombocytopenia
  • Leukopenia
  • Pancytopenia

• Hepatic:

  • Cholestatic Jaundice
  • Hepatotoxicity

• Neuromuscular & Skeletal:

  • Tremor

• Ophthalmic:

  • Corneal Changes
  • Lens Disease
  • Retinitis Pigmentosa

• Respiratory:

  • Nasal Congestion

Contraindications to Trifluoperazine (Stelazine):

• Hypersensitivity to trifluoperazine, Phenothiazines or any other component of the formulation
• CNS depressants can cause comatose and depressed states.
• Suppression of bone marrow
• Blood dyscrasias
• Liver disease

Warnings and precautions

• Modified cardiac conduction

  • Therapeutic doses of antipsychotics can cause life-threatening arrhythmias by altering the cardiac conduction.

• Anticholinergic effects

  • There may be anticholinergic side effects, such as constipation, xerostomia and blurred vision.
  • Patients with reduced gastrointestinal motility, paralytic-ileus, urinary retention (BPH), xerostomia, and visual impairments should be cautious.
  • Trifluoperazine's cholinergic blockade is more potent than other antipsychotics.

• Antiemetic effects

  • Antiemetic effects can mask the toxic effects of certain drugs and conditions, such as Reye syndrome, intestinal obstruction, brain tumor, or Reye syndrome.

• Blood dyscrasias

  • This condition can cause anemia, leukopenia and neutropenia. It can also lead to thrombocytopenia, thrombocytopenia (sometimes fatal), anemia, agranulocytosis, and pancytopenia. Blood counts should be checked periodically for any risk factors, such as low WBC, history of drug-induced leuko/neutropenia, or preexisting low WBC.
  • Stop the therapy immediately if there are any signs of blood disorder or an absolute neutrophil count below 1,000/mm3.

• Depression in the CNS:

  • CNS depression can lead to impairment of mental or physical abilities. Patients should be cautious about driving, operating machinery, and other tasks that require mental alertness.

• Aspiration/Esophageal dysmotility/Esophageal dysmotility

  • Antipsychotics may cause esophageal dismotility and aspiration. This risk increases with increasing age.
  • Patients at high risk of aspiration pneumonia (ie Alzheimer's disease) should be cautious when using this medication, especially patients over 75 years.

• Extrapyramidal symptoms (EPS).

  • Pseudoparkinsonism, acute and chronic dystonic reactions, as well as tardive dyskinesia may all be possible.
  • Higher doses and use of antipsychotics may increase the risk of dystonia in younger patients.
  • These factors increase the likelihood of tardive dyskinesia
    • The golden years
    • Combining female gender with postmenopausal status
    • Parkinson disease
    • Pseudoparkinsonism symptoms
    • Affective disorders, especially major depressive disorder.
    • Concurrent medical conditions such as diabetes and previous brain damage
    • Alcoholism
    • Response to poor treatment
    • High doses of antipsychotics
  • With tardive dyskinesia symptoms or signs, the therapy should be stopped.

• Hepatic effects

  • This may cause liver damage or cholestatic jaundice.

• Hyperprolactinemia

  • Hyperprolactinemia may occur in breast cancer patients.

• Neuroleptic malignant Syndrome (NMS).

  • Use of the device may cause NMS.
  • Monitor patients for changes in mental status, fever, rigidity of the muscles, and/or signs of autonomic instability.
  • It is important to carefully reintroduce the drug after NMS recovery.

• Ocular effects

  • Extended therapy may cause pigmentary retinopathy and lenticular or corneal deposits (Oshika 1995).

• Orthostatic hypotension

  • Orthostatic hypotension can occur during use. Patients at high risk or those who cannot tolerate transient hypotensive episodes should be cautious.

• Temperature regulation

  • It may cause an impairment of core body temperature regulation. Be cautious with heat exposure, dehydration, strenuous exercise, heat, and any concomitant anticholinergic medication.

• Cardiovascular disease

  • Be careful.

• Dementia: [US Boxed Warning]

  • Patients with dementia-related psychosis are at greater risk of death if they receive antipsychotics.
  • The most common causes of death are cardiovascular diseases, such as sudden death, heart failure, and infectious diseases, like pneumonia.
  • Patients with Parkinson's disease dementia or Lewy body dementia should be cautious as they are more likely to experience adverse effects and sensitivity extrapyramidal effects. There is also a higher risk of death or irreversible cognitive impairment.
  • The APA recommends that elderly patients with dementia-related schizophrenia should prefer the 2nd Generation Antipsychotics to the 1st. This is because the 1st antipsychotics have a higher risk of harm than the 2nd.
  • Trifluoperazine has not been approved for treatment of dementia-related psychosis.

• Hepatic impairment

  • Patients with liver disease should not take this medication.

• Seizure disorder

  • Patients at high risk for seizures, including those who have had seizures in the past, should be cautious. 1st-generation antipsychotics can decrease seizure threshold

Trifluoperazine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Mental health
• Vital signs (as indicated by a doctor)
• Weight
• Height
• BMI
• Waist circumference (baseline) at each visit for the first six months. Visit quarterly with stable antipsychotic dosage.
• Complete blood count (as indicated by the doctor; patients with low WBC, or a history of drug-induced neutropenia/neutropenia should be monitored frequently for the first few months).
• Annually, and as clinically indicated, serum electrolytes and liver function
• Fasting plasma glucose/HbA (baseline, then annually for patients with diabetes risk factors, or if you are gaining weight, repeat the 4 month period after taking an antipsychotic. Then, yearly).
• Baseline Lipid Profile; Repeat every 2 years if your LDL level has not changed; Repeat every 6 months if it is higher than 130 mg/dL.
• Changes in menstruation, fertility, and development of galactorrhea (at each visit for 12 weeks after antipsychotic administration or until the dose becomes stable, then annually)
• Parkinsonian signs or abnormal involuntary movements (baseline; continue weekly until dose stabilization for at least two weeks after introduction, and for at most 2 weeks following any significant dose increases)
• Tardive dyskinesia occurs every 6 months, high-risk patients every three months).
• Ask about visual changes every year
• Ocular examination: Annually for patients over 40 years old; once every two years for younger patients

How to administer Trifluoperazine (Stelazine)?

• Oral: To avoid or decreased GI upset, it may be taken with the meal; should not be taken within 2 hours of any antacids

Mechanism of action of Trifluoperazine (Stelazine):

Trifluoperazine, a piperazine-phenothiazine antipsychotic, causes blockade dopamine subtype 2 (D) receptors in the mesolimbocortical (APA) and nigrostriatal (APA).

Start of action It takes between 2 and 4 weeks to control aggression, hostility, agitation, and hostility. 1 week is required for psychotic symptoms (hallucinations or disorganized thinking, behavior, delusions) in order to be controlled. 6 weeks of adequate trial at moderate to high doses, depending on tolerance

Duration of action: Variable

Metabolism: Undergoes metabolism in the gut after administration and in the liver to active metabolites dimethyl trifluoperazine, 7-hydroxyrifluoperazine, and other metabolites (Midha 1984).

Half-life elimination: 3 to 12 hours

Time to peak, serum: 1.5 to 6 hours

International Brand Names of Trifluoperazine:

• Apo-Trifluoperazine
• Befrin
• Domilium
• Espazine
• Flupazine
• Flurazin
• Fuzine
• Jatroneural
• Jatroneural Retard
• Leptazine
• Modalina
• Modiur
• Sizonil
• Stela
• Stelazine
• Stelazine Forte Solution
• Stelazine MR
• Stellasil
• Stelosi
• Sycazine
• Telazine
• Terflurazine
• Terfluzine
• Tridil
• Triflazine
• Triflumed
• Triftazin
• Trinicalm
• Triozine

Trifluoperazine Brand Names in Pakistan: