What is Trilafon used for? A Comprehensive Guide to Perphenazine

October 6, 2025 •

3 min read

First introduced in 1957, Trilafon (perphenazine) is a first-generation antipsychotic primarily used for treating schizophrenia and severe nausea and vomiting. While the brand name is no longer manufactured in the U.S., the generic form is still prescribed for these and other off-label conditions.

Quick Summary

Trilafon, the discontinued brand name for generic perphenazine, is a first-generation antipsychotic medication. Its primary FDA-approved uses are for treating schizophrenia and controlling severe nausea and vomiting in adults. The drug works by blocking dopamine receptors in the brain to regulate mood, behavior, and thoughts.

Key Points

Primary Uses: Trilafon (perphenazine) is FDA-approved for treating schizophrenia and severe nausea and vomiting in adults.
Mechanism: It works by blocking dopamine D2 receptors in the brain to mitigate psychotic symptoms and control vomiting.
Drug Class: Trilafon is a first-generation (typical) antipsychotic belonging to the phenothiazine class.
Generic Availability: The brand name Trilafon has been discontinued in the U.S., but the generic, perphenazine, is widely available.
Notable Side Effects: Potential for serious side effects includes extrapyramidal symptoms and the potentially irreversible movement disorder tardive dyskinesia.
Important Warning: The FDA has issued a boxed warning against its use in older adults with dementia-related psychosis due to an increased mortality risk.
Off-Label Applications: Perphenazine is sometimes used off-label for conditions such as bipolar disorder, severe anxiety, and intractable hiccups.

What is Perphenazine (Trilafon)?

Trilafon is the former brand name for the generic drug perphenazine, a typical (first-generation) antipsychotic medication belonging to the phenothiazine class. It was introduced in 1957 but has largely been replaced by newer, atypical antipsychotics due to its potential for more pronounced neurological side effects. However, perphenazine remains an important and effective option for patients who do not respond to newer agents. Its mechanism of action involves blocking dopamine D2 receptors in the brain, which helps to reduce the overactivity of dopamine that is believed to contribute to psychotic symptoms.

FDA-Approved and Off-Label Uses

Perphenazine is utilized for a range of conditions, both approved by the FDA and prescribed off-label for other therapeutic purposes. Understanding its applications is crucial for proper patient care.

FDA-Approved Indications

Perphenazine has two main FDA-approved indications for use:

Schizophrenia: This is a severe mental illness characterized by disturbed or unusual thinking, hallucinations, delusions, and a loss of interest in life. Perphenazine helps control these symptoms by decreasing abnormal excitement in the brain. It is approved for use in both adults and adolescents 12 years and older for this purpose.
Severe Nausea and Vomiting in Adults: Perphenazine is indicated for the control of severe nausea and vomiting, particularly when other treatments have failed. Its antiemetic effects are attributed to blocking dopamine receptors in the brain's chemoreceptor trigger zone, which is responsible for triggering vomiting.

Off-Label Uses

In some cases, healthcare providers may prescribe perphenazine for conditions not officially approved by the FDA. This practice is known as off-label use and is based on the provider's clinical judgment. Common off-label uses include:

Bipolar Disorder: For managing manic episodes.
Agitated Behavior: For patients with severe agitation.
Severe Anxiety and Depression: Sometimes used in combination with antidepressants like amitriptyline for severe anxiety and depression.
Intractable Hiccups: For persistent, uncontrollable hiccups.

Dosage and Administration

Perphenazine dosage should always be determined by a healthcare professional based on the individual patient's condition and response to treatment. It is administered orally. When discontinuing the medication, a gradual dose reduction is necessary to avoid withdrawal symptoms.

Key Side Effects and Safety Warnings

As a typical antipsychotic, perphenazine carries a risk of side effects, some of which can be severe. It is essential for patients and caregivers to be aware of these risks.

Common Side Effects

Drowsiness or dizziness
Dry mouth
Blurred vision
Constipation
Unexplained weight gain

Serious Side Effects

Extrapyramidal Symptoms (EPS): Drug-induced movement disorders such as tremors, rigidity, restlessness (akathisia), and involuntary muscle spasms (dystonia).
Tardive Dyskinesia: A potentially irreversible movement disorder that can develop with long-term use, causing repetitive, involuntary movements of the face, tongue, and limbs.
Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening condition characterized by high fever, muscle stiffness, altered mental status, and irregular heartbeat.
Increased Risk of Death in Older Adults: The FDA has issued a boxed warning stating that antipsychotics like perphenazine increase the risk of death in older adults with dementia-related psychosis, and it is not approved for this use.

Comparison of Perphenazine with Other Antipsychotics

Perphenazine is an older, first-generation antipsychotic, which differs from newer, second-generation (atypical) antipsychotics. The comparison below highlights some key differences in their use and side effects. For more detailed information, consult the official MedlinePlus Drug Information on perphenazine.


Feature	Perphenazine (Trilafon)	Aripiprazole (Abilify)	Risperidone (Risperdal)
Drug Class	First-Generation (Typical) Antipsychotic	Second-Generation (Atypical) Antipsychotic	Second-Generation (Atypical) Antipsychotic
FDA-Approved Uses	Schizophrenia, Severe Nausea/Vomiting	Schizophrenia, Bipolar I Disorder, Tourette's	Schizophrenia, Bipolar Disorder, Irritability with Autism
Administration	Oral tablets	Oral, injectable	Oral tablets, oral solution
EPS Risk	Higher risk, especially with higher doses	Lower risk compared to typicals	Risk present, especially at higher doses
Metabolic Risk	Lower risk of weight gain compared to some atypicals	Can increase blood sugar and cholesterol	Can cause weight gain

Conclusion

Trilafon, known generically as perphenazine, is a well-established first-generation antipsychotic primarily used to manage schizophrenia and severe nausea. Its efficacy, particularly for patients unresponsive to other treatments, is significant. However, its use requires careful consideration due to the potential for severe side effects, including irreversible tardive dyskinesia. Healthcare providers must weigh the benefits against these risks, especially in vulnerable populations like older adults with dementia. While the brand name Trilafon has been discontinued, the generic perphenazine remains a valid and important therapeutic option when used under close medical supervision.

Important Safety Note

Never stop taking perphenazine suddenly without consulting a doctor, as this can lead to unpleasant withdrawal symptoms. Always follow the precise directions provided by your healthcare provider.

Frequently Asked Questions

Trilafon was the brand name for the drug perphenazine. The brand name has been discontinued in the U.S., but the generic version, perphenazine, is still available and is the same medication.

Perphenazine is not FDA-approved to treat anxiety alone. However, a combination medication containing both perphenazine and the antidepressant amitriptyline is approved for treating moderate-to-severe anxiety and depression. In some cases, perphenazine may be used off-label for severe anxiety, but this must be determined by a healthcare provider.

Studies have shown that perphenazine can cause both weight gain and weight loss. It is less likely to cause significant weight gain compared to some other antipsychotics, but it is a potential side effect.

Extrapyramidal symptoms (EPS) are drug-induced movement disorders that can be a side effect of perphenazine. They include tremors, rigidity, restlessness (akathisia), muscle spasms, and a shuffling walk.

Tardive dyskinesia is a potentially irreversible movement disorder that can occur with long-term use of typical antipsychotics like perphenazine. It involves uncontrolled, repetitive movements of the face, mouth, and limbs.

No, the FDA has issued a boxed warning indicating that antipsychotic medications like perphenazine increase the risk of death in older adults with dementia-related psychosis. It is not approved for this use.

If you miss a dose of perphenazine, take it as soon as you remember. If it is close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. Always consult with your healthcare provider if you are unsure about what to do after missing a dose.