Dr. Jenni Jacobsen, PhD
Author: Dr. Jenni Jacobsen, PhD Medical Reviewer: Dr. Leila Khurshid Last updated:

Perphenazine is an antipsychotic medication used in the treatment of schizophrenia and other psychotic disorders. It belongs to a class of medications called first-generation or typical antipsychotic drugs, which should be taken as prescribed because they can cause severe adverse effects.[1]

Perphenazine brand names

Perphenazine is found under the following brand names [2]:

  • Trilafon
  • Duo-Vil (perphenazine with amitriptyline)
  • Etrafon (perphenazine with amitriptyline)
  • Triavil (perphenazine with amitriptyline)

What is perphenazine prescribed for?

As a typical antipsychotic, perphenazine is most often prescribed for the treatment of schizophrenia. It is also effective for treating severe nausea and vomiting and may be prescribed for this purpose [2].

Typical antipsychotics like perphenazine may also be prescribed for the following conditions [1]:

  • Mania: Sometimes, people who experience manic episodes throughout bipolar disorder also show features of psychosis. In this case, perphenazine may be beneficial.
  • Major depression: In rare cases, depression may lead to symptoms of psychosis, making perphenazine a suitable treatment option.
  • Delusional disorder: This mental health condition is often treated with antipsychotic medications [3].
  • Severe behavioral disturbances: Severe behavioral disturbances involving agitation or hostility may be treated with a short-term regimen of antipsychotic medications.
  • Borderline personality disorder: Because this condition may involve symptoms of psychosis and paranoia, a first-generation antipsychotic like perphenazine may be used to treat it.

How does perphenazine work?

Perphenazine works to treat psychosis and other symptoms of schizophrenia because of its actions on a brain chemical called dopamine. In people with symptoms of psychosis, dopamine levels are believed to be too high. Therefore, perphenazine and other first-generation antipsychotics block the activity of dopamine in the brain, reducing psychotic symptoms arising from elevated dopamine activity.[1]

How is perphenazine usually taken?

Perphenazine is typically taken orally in pill form. Patients often take oral tablets 4 to 8 mg three times per day. The medication can also be administered parenterally, which means it is injected into the body.[1]

A patient’s dosing regimen can vary based on their unique needs, health status, and the severity of their condition. A doctor will determine the best dose for each individual patient and will provide instructions for how to take perphenazine.

How long does perphenazine stay in your system?

Perphenazine has a half-life of 8-12 hours, with an average of 9.5 hours. In some cases, the half-life may be as long as 20 hours.[4] The half-life of a medication refers to the length of time it takes for half of one dose to be removed from the body.[5]

This means after about 9.5 hours, the concentration of perphenazine decreases to half the initial dose taken. A drug is eliminated from the body after 4 to 5 half-lives [5], so you can expect perphenazine to stay in your system for an average of about 38 to 47.5 hours, or between 1 ½ to two days.

Perphenazine side effects

First-generation or typical antipsychotics like perphenazine can have several side effects, which are described in more detail below.

Common or Mild Perphenazine Side Effects

The following common side effects are relatively mild with perphenazine and often are not serious and do not require medical attention[2]:

  • Feeling dizzy
  • Being unsteady on feet or having a difficult time maintaining balance
  • Widening or narrowing of pupils in the middle of the eyes
  • Pale skin or change in skin color
  • mild itching
  • Either dry mouth or excessive saliva
  • loss of appetite
  • nasal congestion
  • Headache
  • Nausea and vomiting
  • Diarrhea or constipation
  • Lack of control of facial expressions
  • Unusual or uncontrollable body movements
  • Feeling restless
  • Orthostatic hypotension (Postural hypotension)
  • Sleep disturbances and unusual dreams
  • A sense of being threatened by others
  • Frequent urination or difficulty urinating
  • Breast enlargement or production of breast milk
  • Skipped menstrual periods
  • Sexual problems

If the above side effects persist, are severe, or begin to interfere with daily functioning, talk with your doctor, who can advise you on the best course of action.

Rare or Severe effects of Perphenazine

While the following side effects may not be as common, they are considered severe. Contact your doctor immediately or seek medical attention if you experience any of the following [2]:

  • High fever
  • Stiffness in muscles
  • Mouth sores
  • Falls
  • Confusion
  • Elevated heart rate
  • Sweating
  • Lack of thirst
  • Cramping in the neck
  • Tongue sticking out of the mouth
  • Tightness in throat
  • Raised blood pressure
  • Having a hard time breathing or swallowing
  • Uncontrollable movements in the face, mouth, or jaw
  • Seizures
  • Eye pain or discoloration
  • Seeing everything in a brown tint or losing vision
  • Yellowing of the skin and eyes
  • Development of a rash
  • Urinary retention
  • Decrease in white blood cell count
  • Hives or itching
  • Swelling in the eyes, face, mouth, lips, tongue, throat, arms, hands, feet, ankles, or lower legs
  • Signs of infection, such as sore throat, fever, or chills
  • Slow heart rate
  • Allergic reaction
  • Neuroleptic malignant syndrome (NMS)

Perphenazine precautions

Before taking perphenazine, it’s important to tell your doctor if you have any other health conditions or are using any other medications. Sometimes, perphenazine can be dangerous, depending on your particular health condition. It can also interact negatively with other medications you might be taking.

If you have liver disease, brain damage, trouble maintaining balance, or conditions that affect your blood cells, it may be unsafe for you to take perphenazine. Perphenazine can also cause problems when taken during pregnancy, so it’s important to tell your doctor if you’re pregnant or planning to become pregnant.[2]

Other health conditions that may make it dangerous for you to take perphenazine include a tumor on the gland near the kidneys, a history of seizures, breast cancer, an abnormal EEG, asthma, emphysema, lung infection, heart disease, or kidney disease.[2]

Other precautions to consider are that perphenazine can make you tired, so it’s important to wait to see how this medication affects you before you drive or operate heavy machinery. It may be unsafe to consume alcohol while on perphenazine, as it can worsen side effects. You may also be more sensitive to sunlight when taking the medication and overheat when exposed to extreme heat or when exercising vigorously.[2]

The list herein is not exhaustive. Talk with your doctor about any precautions you should know or follow when taking perphenazine.

Perphenazine interactions

Perphenazine may interact with other medications you are taking, so it’s important to be aware of potential interaction effects. The following medications may interact with perphenazine [2]:

  • Cordarone
  • Pacerone
  • Antidepressant medications
  • Antihistamines
  • Motofen, Lomotil, or Lonox
  • Barbiturates
  • Bupropion (Aplenzin, Wellbutrin, Zyban)
  • Chlorpheniramine, contained in cough and cold medicines
  • Tagamet
  • Anafranil
  • Cymbalta
  • Epipen
  • Haloperidol
  • Atrovent
  • Any medications taken for anxiety disorders or other mental health conditions
  • Medications taken to treat irritable bowel syndrome
  • Medications used to treat motion sickness
  • Anti-seizure medications
  • Medications to treat Parkinson’s disease
  • Methadone or other narcotic pain medications
  • Medications used to treat ulcers
  • Medications used in the treatment of urinary problems
  • Quinidine
  • Norvir
  • Sedative drugs
  • SSRIs, including Prozac, Paxil, Pexeva, and Zoloft
  • Sleeping pills or tranquilizers

The above list is not exhaustive, but these medications may interact with perphenazine. Be sure to talk to your doctor about these or any other medications you are taking.

If you’re taking a medication that could interact with perphenazine, your dose may need to be adjusted, or your doctor may carefully monitor you for side effects. In some situations, perphenazine may not be suitable for you if you must take a medication that could interact with it.

Perphenazine storage

Perphenazine should be stored in its original prescription container to prevent someone from mistakenly taking this medication. The container should be tightly sealed, and it should be kept away from excessive heat or moisture. A bathroom is not an ideal location to store perphenazine.[2]

What to do if you overdose on perphenazine

Taking too high of a dose of perphenazine can result in overdose symptoms, including the following [2]:

  • Seizures
  • Elevated or irregular heart rate
  • Coma
  • Inability to respond to surroundings

If a person has overdosed on perphenazine and collapsed, has a seizure, or cannot breathe, it is critical to call 9-1-1 or seek immediate medical attention.


People commonly have the following question about perphenazine:

What’s the difference between perphenazine and fluphenazine?

Both perphenazine and fluphenazine belong to the first-generation or typical antipsychotic class of drugs. Some research suggests that perphenazine may be more effective than fluphenazine, but the two medications have a similar risk of causing side effects.[6]

  1. Chokhawala, K., & Stevens, L. Antipsychotic medications. (2022). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from
  2. Perphenazine: MedlinePlus Drug Information. (2018 February 15) National Library of Medicine. Retrieved November 2, 2022, from
  3. Joseph, S.M., & Siddiqui. W. Delusional disorder.(2022). In: StatPearls [Internet].Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
  4. National Center for Biotechnology Information. (2022). PubChem Compound Summary for CID 4748, Perphenazine. Retrieved November 2, 2022 from
  5. Hallare, J., & Gerriets, V. Half Life. (2022). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from,starting%20dose%20in%20the%20body.
  6. Hartung, B., Sampson, S., & Leucht, S. (2015). Perphenazine for schizophrenia. Cochrane Database of Systematic Reviews.
Medical Content

Our Medical Affairs Team is a dedicated group of medical professionals with diverse and extensive clinical experience who actively contribute to the development of our content, products, and services. They meticulously evaluate and review all medical content before publication to ensure it is medically accurate and aligned with current discussions and research developments in mental health. For more information, visit our Editorial Policy.

About is a health technology company guiding people towards self-understanding and connection. The platform offers reliable resources, accessible services, and nurturing communities. Its mission involves educating, supporting, and empowering people in their pursuit of well-being.

Dr. Jenni Jacobsen, PhD
Author Dr. Jenni Jacobsen, PhD Medical Reviewer, Writer

Dr. Jenni Jacobsen, PhD is a medical reviewer, licensed social worker, and behavioral health consultant, holding a PhD in clinical psychology.

Published: Nov 22nd 2022, Last edited: Nov 10th 2023

Dr. Leila Khurshid
Medical Reviewer Dr. Leila Khurshid PharmD, BCPS

Dr. Leila Khursid is a medical reviewer with a Doctor of Pharmacy degree and completed a PGY1 Pharmacy Residency from St. Mark's Hospital.

Content reviewed by a medical professional. Last reviewed: Nov 23rd 2022