Perphenazine is one of the first generation of antipsychotic medications. It belongs to a class of drugs known as phenothiazine derivatives. It was sold for many years under the brand name Trilafon, which is no longer being manufactured. It is still available, however, as a generic medication.

What it’s used to treat

Perphenazine is used primarily for the treatment of schizophrenia. It is also approved for the treatment of individuals experiencing extreme bouts of nausea and vomiting.

How it works

As with all antipsychotics, it is not fully understood just how perphenazine works in the brain to reduce and alleviate schizophrenic symptoms. However, it appears to work primarily on two neurotransmitters: norepinephrine and dopamine. These brain chemicals are believed to be out of balance in the brains of people who experience psychotic episodes, which is typical in schizophrenia. As with all similar medications, it only helps to control the symptoms of schizophrenia; it does not cure the disorder.

How it’s administered

Perphenazine is available in tablet form and liquid form, to be taken orally. It is also available as an injection.

Potential Side Effects

Perphenazine, like all medications, may cause many potential side effects. Some of the more common side effects include:

  • Sleepiness
  • Blurred vision
  • Headaches
  • Dry mouth
  • Problems urinating
  • Difficulties sleeping
  • Nausea and vomiting
  • Constipation or diarrhea
  • Changes in libido
  • Sun sensitivity
  • Problems with ejaculation
  • Decreased appetite
  • Nasal congestion

Some other less common potential side effects include (but are not limited to) irregular heart beat, increase in breast size or unusual breast discharge (in both sexes), changes in blood sugar levels and seizures.

As with other antipsychotic medications, perphenazine may also cause tardive dyskinesia (TD) and neuroleptic malignant syndrome (NMS).

Tardive dyskinesia can become a permanent condition for some individuals, although in some cases it does resolve. TD symptoms involve involuntary, random and uncontrollable movements, such as lip smacking, odd tongue or jaw movements, blinking, grimacing, and movements involving the limbs, fingers, toes, upper body or hips.

Neuroleptic malignant syndrome is very serious because it can be fatal. Some of the symptoms include muscle stiffness, changes in one’s mental state, fluctuations in blood pressure or heartbeat, sudden renal failure, tremors, difficulty breathing, dehydration, rapid heartbeat, and extremely high temperature.


As with all medications, there are numerous precautions to be considered before taking perphenazine. Perphenazine can cause an increased sensitivity to sun exposure, so if you take this medication you should use sunscreen, particularly if you have fair skin. Also, be sure to inform your doctor if you have a history of bone marrow depression, any type of brain damage, or if you have ever been in a coma. Be sure to let your doctor know about any drug allergies or medications you are currently taking.

Prior to taking perphenazine if you or a family member has a history of serious breathing difficulties or asthma, glaucoma, epilepsy, heart disease or cardiovascular problems, kidney or liver disease, or prostrate conditions. Also, if you are nursing or pregnant, or planning to become pregnant, be sure to inform your doctor.

If you start taking perphenazine and decide to discontinue using it, do not stop suddenly. Rather, gradually decrease the dose under the supervision of your doctor.

written by Dr. Cheryl Lane, PsyD