Perphenazine (Trilafon): Uses, Side Effects, Dosage, & More

What Is Perphenazine (Trilafon)?

Perphenazine is an older class of first-generation (typical) antipsychotic drugs that belong to the piperazinyl phenothiazine class. Its main effects are regulation of mood, thoughts, and behavior, and also sedation. Its FDA-approved uses are for treating schizophrenia, severe nausea, vomiting, and uncontrollable hiccups in individuals above 12 years of age. This article will focus on its use as a treatment for schizophrenia. Perphenazine is available only as a generic medication. Trilafon, the brand name of perphenazine, was discontinued in the United States.

FDA approval means the drug is determined to provide benefits that outweigh its known and potential risks for the intended population. Due to the high risk of death, perphenazine use is not appropriate in older adults with impaired memory associated with mental illness.¹

Is Perphenazine Good for Anxiety?

Perphenazine may help symptoms of anxiety and agitation as it helps regulate the dopamine levels in the brain. For some, this may reduce stress, tension, aggression, and anxiety without affecting alertness or cognitive insight. It is a relatively safe and effective calming drug appropriate for several anxiety-related health conditions.²

Using perphenazine for anxiety would be an off-label use. An off-label use of a medication is a use that is not FDA-approved. Prescribers can decide to use a medication off-label because, in their professional judgment, they believe it may offer a benefit to a patient.

How Does Perphenazine Work?

Perphenazine is thought to affect dopamine levels by influencing receptors in the brain. Research has shown that symptoms of schizophrenia, bipolar disorder, and major depressive disorder may be related to abnormalities in dopamine levels. Dopamine is a brain chemical linked with emotional regulation.^{3, 4, 5}

What Is Perphenazine Used to Treat?

Perphenazine is FDA-approved to treat schizophrenia in adults and children who are 12 years of age and older and severe nausea and vomiting in adults. FDA approval means the drug is determined to provide benefits that outweigh its known and potential risks for the intended population.

Its non-FDA-approved (off-label) uses are for manic episodes of bipolar disorder, agitated behavior, severe anxiety, and depressed mood.^{5, 6} An off-label use of a medication is a use that is not FDA-approved. Prescribers can decide to use a medication off-label because, in their professional judgment, they believe it may offer a benefit to a patient.

Common Side Effects of Perphenazine

Some individuals may experience abnormal movements due to the use of medications, including antipsychotics such as perphenazine. Their severity and frequency typically increase with higher drug doses and may differ among individuals. Drowsiness may occur in the first or second week but generally disappears over time. If these symptoms occur, your doctor may adjust the dose or add another drug to address them effectively.

Common side effects of perphenazine include:¹

• Feeling restless (akathisia), inability to sit still
• Uncontrollable shaking (tremors), slow movements, and stiffness (parkinsonian-like syndrome)
• Lack of balance, coordination, and trouble walking (ataxia)
• Tongue protrusion, puffing of cheeks, puckering of mouth, chewing movements (persistent tardive dyskinesia)
• Throat tightness, slurred speech, breathing and swallowing difficulty (dystonia)
• Lockjaw (trismus)
• Blurred and painful vision (oculogyric crisis)

*All medications, including perphenazine, can cause side effects which can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and to understand the potential side effects and benefits of any medication.

Serious Side Effects of Perphenazine

The drug has the potential to cause serious side effects. While these are uncommon, serious side effects require immediate medical care.

Serious side effects of perphenazine include:¹

• Convulsive seizures
• Life-threatening allergic reaction (multiple organs including brain swelling; cerebral edema)
• Neuroleptic malignant syndrome (high fever, altered mental status, heavy sweating, irregular pulse, blood pressure, and heartbeat)
• Shock-like condition (low blood pressure), falls and fractures, or other injuries
• Sudden death due to heart failure
• Infections due to reduced white blood cell count (agranulocytosis)
• Paralysis of the digestive tract (adynamic ileus)
• Jaundice, liver damage (biliary stasis)
• Systemic lupus erythematosus-like syndrome (tiredness, skin rashes, fevers, pain or swelling in the joints)
• Worsening of psychotic symptoms (restlessness, sleeplessness, hyperactivity, confusion, and bizarre dreams)

*All medications, including perphenazine, can cause side effects which can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and to understand the potential side effects and benefits of any medication.

Perphenazine Warnings & Precautions

Discuss any health conditions, drugs, or allergies with your doctor before you begin using perphenazine. As with any medication, using perphenazine comes with risks and precautions to be aware of.

Use this drug cautiously if you have a history of harmful reactions to other phenothiazine drugs, as severe effects may frequently appear when taking high drug doses. A significant rise in body temperature may suggest individual intolerance to perphenazine, and drug discontinuation or close supervision is essential.

You may need to avoid taking perphenazine if you:¹

• Are diagnosed with dementia-related psychosis: The risk of death in older adults is high if they take medications for mental problems related to dementia. Most of the deaths are due to heart disease or infection.
• Have allergic reactions: Tell your doctor about the drug allergy and reactions you had like rash, itching, red, swollen, blistered, or peeling skin, wheezing, chest or throat congestion, trouble breathing, swallowing, or talking, unusual mouth, face, lips, or tongue swelling.
• Neuroleptic Malignant Syndrome: A dangerous reaction to antipsychotic medications that can lead to many symptoms, including muscle stiffness and an altered mental status. It can cause death in some cases.
• Have a history of low blood cell counts: A history of drug-induced or pre-existing low white blood cell (WBC) count may increase the risk of infections and fever during antipsychotic treatment. Individuals must have frequent complete blood count (CBC) assessments during the initial treatment.
• Use alcohol: Individuals must avoid alcohol because the combination may worsen drowsiness and sedation and impair thinking, judgment, and coordination. There is a risk of suicide, drug overdose, and low blood pressure.
• Have a history of depression: Due to the increased risk of suicidal thoughts while using perphenazine, individuals with a history of depression should avoid having access to large amounts of this medication.
• Have sunlight exposure: Photosensitivity may occur during the treatment. Avoid prolonged sunlight (UV), tanning booths, and sunlamps, as they may cause redness and swelling (sunburn) on patches of sun-exposed skin. Use sunscreen (SPF 30 or higher) and wear protective clothing outdoors.⁷
• Increased risk of falls: Potential side effects caused by perphenazine can lead to an increased risk of falls. This is particularly dangerous for people who are already at risk of falls due to a disease or medication.
• Have liver and kidney problems: The drug should be used cautiously due to the risk of jaundice and kidney failure. Liver and kidney functions should be checked periodically during the treatment.
• Are undergoing surgery: Use the drug with caution during surgery or dental work. Fewer doses of anesthesia or central nervous system depressants may be necessary due to prolonged and additive sedative effects.

Perphenazine Dosages for  FDA-Approved Treatment

Perphenazine is available in tablet forms for treating schizophrenia with a dose range from 4 mg to 8 mg three times daily initially, followed by dose reduction to a minimum effective dose. If given in the hospital, doses may range from 8 mg to 16 mg two, three, or four times daily with a max daily dose of 64 mg per day. The dose ranges from 8 mg to 16 mg daily in divided doses for severe nausea and vomiting. However, sometimes 24 mg may be necessary with early dose reduction.¹

The dose may be individualized and adjusted based on the severity of the health condition and drug response.⁸

Perphenazine Forms & Strengths

Perphenazine is available as a tablet with dose strengths ranging from 2 mg to 16 mg. Lower doses for a longer duration may benefit older adults. Additionally, bedtime doses are favorable due to their calming and blood pressure-lowering effects.¹ It is only available as a generic medication.

Beginning with the lowest effective dose is crucial since side effects increase with higher dosages. Initial improvement in symptoms of schizophrenia may occur within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks.⁹ However, research has shown that the drug can control postoperative nausea and vomiting in the early postoperative period within 6 hours of the first dose.¹⁰

Perphenazine is available in the following forms and strengths:¹

• 2 milligrams (mg) oral tablet
• 4 mg oral tablet
• 8 mg oral tablet
• 16 mg oral tablet

How Should I Take Perphenazine?

You can swallow perphenazine tablets with water two to four times daily as prescribed, preferably at the same time each day. Your doctor may start a lower dose first to avoid the risk of muscle spasms, then gradually increase it. There may be the risk of harmful withdrawal effects if you stop or alter the drug dose suddenly.

Inform your doctor immediately if your symptoms do not improve or worsen. Since the drug has calming and drowsy effects, it is crucial to avoid taking it during the daytime. Follow your doctor’s instructions carefully and regularly take the drug to achieve the best results.

What Happens If I Miss a Dose of Perphenazine?

If you forget to take a dose of your medication, take it as soon as you remember. However, if the time for your next dose is almost here, skip the missed one and take the next scheduled drug dose. Never take a double dose to make up for the missed one. It may cause unpleasant stomach pain, dizziness, vomiting, shakiness, and restlessness on sudden discontinuation of the drug. Therefore, always consult your care team before discontinuing this drug.¹¹

If you have missed a dose and aren’t sure if you should take it, contact your pharmacist or healthcare professional.

Can You Overdose on Perphenazine?

Consuming high doses of perphenazine or combining it with other central nervous system depressants, such as alcohol, narcotics, or painkillers, can lead to a drug overdose. Moreover, older adults may be more prone to overdose symptoms even when they take the prescribed amount of the drug due to their slow body metabolism.

Overdose symptoms can be mild or severe, ranging from low blood pressure, slow breathing, fainting, and dizziness to more severe symptoms like seizures, irregular pulse, or even coma. Therefore, it’s crucial to seek immediate emergency treatment by calling 911 and going to the nearest hospital if you suspect an overdose.

What Should You Do If You Take Too Much Perphenazine?

If someone overdoses on perphenazine, immediately take them to the emergency room or dial 9-1-1. Typically, the treatment is supportive and symptomatic. Healthcare providers may provide oxygen, hydrate you with IV fluids, and use medications to help reduce the harmful effects of overdose.

What to Avoid When Taking Perphenazine

Some substances can create unsafe interactions when used with perphenazine. Some may lead to life-threatening side effects and even death due to drug interactions. Individuals oversensitive to perphenazine products or related substances should not use perphenazine.

You may need to avoid or take precautions with the following substances while taking perphenazine:¹

• Tricyclic antidepressants (TCAs): TCAs, such as amitriptyline, imipramine, or doxepin may increase the perphenazine levels in the bloodstream. This may increase the risk of drowsiness, dry mouth, and muscle spasms.
• Selective serotonin reuptake inhibitors (SSRIs): SSRIs, such as fluoxetine, sertraline, and paroxetine, may enhance the side effects of antipsychotic drugs. Using them with perphenazine may increase the risk for neuroleptic malignant syndrome.
• Bupropion: Bupropion is associated with a dose-related risk of seizures and may also lower the threshold for triggering a seizure.
• Barbiturates: Using butalbital, pentobarbital, or phenobarbital with perphenazine can increase the others’ effects, which may be harmful.
• Drugs for Parkinson’s disease: Using bromocriptine, levodopa, or pergolide with perphenazine may diminish its effects. Another drug for Parkinson’s disease, pimavanserin, may be used as an alternative.
• Opioids: Using codeine and hydrocodone as pain or cough relievers with perphenazine may lead to excessive sedation.
• Marijuana (cannabis): Cannabinoid products may cause excessive sedation and somnolence when used with perphenazine.
• Drugs for sleep or anxiety: Benzodiazepines like alprazolam, lorazepam, and zolpidem may cause unusual drowsiness and sedation when taken with perphenazine. If directed to take both medications, your doctor may monitor the dose and duration.
• Muscle relaxants: Carisoprodol and cyclobenzaprine can increase the CNS-depressant action of perphenazine. Simultaneous use of these drugs can cause low blood pressure, excessive sedation, dizziness, and impaired mental alertness.
• Antihistamines: Cetirizine and diphenhydramine can increase hallucinations, drowsiness, blurry vision, and sedative effects when used with perphenazine.

This is not a comprehensive list of the possible interactions with perphenazine. You should talk with your healthcare provider and your pharmacist about all prescription and over-the-counter medications, herbs, and supplements you take before starting perphenazine.

How to Get a Prescription for Perphenazine

Perphenazine requires a prescription from medical professionals like neurologists, internists, general or family practitioners, pediatricians, and psychiatrists. Your provider will assess your condition and determine whether a prescription for perphenazine may be an appropriate treatment for you.

Questions to Ask Your Healthcare Provider About Perphenazine

If you have any questions about taking perphenazine, your doctor, psychiatrist, and therapist can help you understand how it might benefit your symptoms and any potential risks involved. You may also consider online psychiatry services a convenient option for receiving similar care as in-office visits.

Questions to ask your care team about perphenazine include:

• How safe is perphenazine?
• How long will it take for me to adjust to taking perphenazine?
• Am I at risk for more serious symptoms if I am already taking other drugs?
• What is the best drug dose to ensure fewer side effects?
• How is this drug best taken?
• Can I stop taking perphenazine if I feel better or don’t notice any improvement?
• Can I increase the drug dose for faster recovery?
• Will I experience withdrawal effects after stopping perphenazine?
• How long does it take for the perphenazine to work?
• What do I need to tell my doctor before I take perphenazine?
• What are some side effects that I need to call my doctor right away?
• What other substances may interact with perphenazine?
• Are there any risks in taking perphenazine for a long time?