Perphenazine is an antipsychotic drug. From the chemical point of view the drug is a phenothiazine and is considered a medium power antipsychotic.

Perphenazine - Chemical Structure


For what it uses

The use of perphenazine is indicated for the treatment of:

  • Schizophrenia;
  • Paranoid states;
  • Mania;
  • Toxic psychosis induced by amphetamines, LSD, cocaine, etc .;
  • Organic mental syndromes accompanied by delirium;
  • Severe anxiety disorders resistant to therapy with typical anxiolytics;
  • Depression accompanied by agitation and delirium (in association with antidepressants);
  • Uncontrollable vomiting and hiccups;
  • Treatment of intense pain (usually in association with opioid analgesics).


The anti-emetic effect of perphenazine may mask the symptoms of overdose of other drugs or the onset of diseases of the gastrointestinal tract or central nervous system.

Since perphenazine can cause hyperprolactinaemia (increased amount of the hormone prolactin in the bloodstream), the drug should be used with caution in women with breast cancer.

Due to the side effects of perphenazine affecting the central nervous system, liver, bone marrow, eyes and the cardiovascular system, periodic clinical and laboratory checks are required.

Perphenazine should be administered with caution in patients with epilepsy or convulsive disorders, since the drug is able to lower the seizure threshold and thus favor the appearance of crisis.

Perphenazine may increase muscle stiffness in patients with Parkinson's disease or other motor disorders.

In the event of the onset of neuroleptic malignant syndrome, treatment with perphenazine should be stopped immediately.

Patients on perphenazine therapy should avoid excessive sun exposure and should use protective creams.

Perphenazine may modify the thermoregulation mechanisms, therefore the drug should be used with caution in patients exposed to very high or very low temperatures.

Patients on perphenazine therapy who need to undergo surgery may require a lower dose of anesthetics.

Perphenazine should be used with caution in patients suffering from cardiovascular diseases and / or with a family history of prolongation of the QT interval (the interval of time required by the ventricular myocardium to depolarize and repolarize).

Since perphenazine promotes the formation of blood clots, it must be administered with caution in patients who suffer - or who have suffered - from bleeding disorders.

Caution should be used in the administration of perphenazine in patients with renal disease.

Perphenazine may induce effects capable of altering the ability to drive and / or use machinery.


Caution should be exercised in the co-administration of perphenazine and other drugs capable of depressing the central nervous system. Among these drugs, we find:

  • Barbiturates ;
  • Anxiolytics ;
  • Anesthetics ;
  • Antihistamines ;
  • Meperidine and other opioid analgesics .

Perphenazine may cause changes in blood levels of phenytoin (a drug used to treat epilepsy).

The combination of perphenazine and lithium (a drug used to treat bipolar disorders) can cause - although rarely - acute encephalopathy, therefore caution should be used.

Perphenazine can antagonize the effect of some antihypertensive drugs, such as - for example - guanethidine . Conversely, the simultaneous use of perphenazine and methyldopa or -blockers (also drugs used to treat hypertension) may increase their hypotensive effects.

Concomitant administration of perphenazine and anticholinergic drugs should be performed with caution, due to the side effects that may occur.

Myelosuppression (bone marrow suppression) induced by perphenazine may be increased if the drug is administered concomitantly with myelotoxic drugs (toxic to the bone marrow).

Metrizamide (a compound used as a contrast agent) increases the risk of convulsions that can be induced by perphenazine.

Perphenazine can antagonize the effect of anti-Parkinson drugs, such as - for example - levodopa .

The use of antacid drugs decreases the absorption of perphenazine.

The risk of occurrence of cardiac arrhythmias increases when perphenazine is administered concomitantly with drugs that increase the QT interval .

Perphenazine should not be administered simultaneously with drugs that cause electrolyte disturbances.

Alcohol intake may potentiate the effects of perphenazine. Furthermore, in alcohol abusers, there is an increased risk of overdose and suicide attempts.

Side effects

Perphenazine can induce different types of side effects, although not all patients experience them.

The following are the main adverse effects that can occur following the use of perphenazine.

Nervous system disorders

Perphenazine treatment can cause various side effects on the nervous system, including:

  • Opisthotonus (spasm of the musculature along the vertebral column which leads the individual to assume an anomalous "bridge" position);
  • Trismus (spastic contraction of the jaw muscles);
  • Stiff neck;
  • Pain and numbness in the limbs;
  • Motor restlessness;
  • Inability to stand still;
  • Dystonia;
  • Parkinson-like symptoms;
  • Dyskinesia;
  • Ataxia;
  • Seizure crises;
  • Drowsiness.

In addition, the drug can cause persistent tardive dyskinesia, especially in women and elderly patients undergoing high-dose perphenazine therapies. However, this effect can also occur in men and children and, sometimes, even following low-dose drug therapies.

Malignant Neuroleptic Syndrome

Neuroleptic Malignant Syndrome is a neurological disorder characterized by:

  • Temperature;
  • Dehydration;
  • Muscle stiffness;
  • akinesia;
  • Sweating;
  • Tachycardia;
  • Arrhythmia;
  • Changes in the state of consciousness that can progress to stupor and coma.

In the event of such symptoms, it is necessary to immediately stop the therapy with perphenazine and contact the doctor immediately.

Psychiatric disorders

Perphenazine therapy may cause:

  • Paradoxical aggravation of psychotic symptoms;
  • Paranoid reactions;
  • Restlessness;
  • Hyperactivity;
  • Confusion;
  • Lethargy;
  • Bizarre dreams;
  • Catatonic-like states;
  • Insomnia.

Gastrointestinal disorders

Perphenazine may cause nausea, vomiting, diarrhea or constipation, gastric retention, fecal impaction and paralytic ileus (sometimes followed by complications and a fatal outcome). Furthermore, the drug can promote the onset of anorexia.

Renal and urinary tract disorders

Treatment with perphenazine may cause urinary retention, increased frequency of urination, incontinence, bladder paralysis and polyuria (ie the formation and excretion of an excessive amount of urine).

Eye disorders

Perphenazine therapy can cause miosis (constriction of the pupil) or mydriasis (dilation of the pupil), impaired vision and favor the onset of glaucoma, retinal changes and pigmentary retinopathy.


Treatment with perphenazine can depress bone marrow activity with consequent decrease in blood cell production. This can cause:

  • Anemia (decrease in hemoglobin blood levels), the main symptom of the onset of anemia is the feeling of physical exhaustion;
  • Leukopenia (decreased white blood cell levels), with increased susceptibility to contraction of infections;
  • Plateletopenia (decrease in the number of platelets), this leads to the appearance of bruising and abnormal bleeding with an increased risk of bleeding.

Allergic reactions

Perphenazine can trigger allergic reactions in sensitive individuals. These reactions can occur in the form of hives, erythema, eczema, exfoliative dermatitis, pruritus, photosensitivity reactions, asthma, fever, anaphylactoid reactions and laryngeal edema.

In some cases cerebral edema, circulatory collapse and death have occurred.

Reproductive system and breast disorders

Perphenazine therapy may cause:

  • Galactorrhea, that is abnormal secretion of milk, both in women and in men;
  • Gynecomastia, that is abnormal development of the breasts in men;
  • Ejaculation inhibition;
  • Breast enlargement in women;
  • Menstrual cycle disorders;
  • Amenorrhea (absence of menstrual cycle).

Endocrine disorders

Perphenazine may cause hyperprolactinaemia and may favor the onset of the syndrome of inappropriate secretion of the antidiuretic hormone (SIADH).

Cardiovascular disorders

Perphenazine treatment may cause orthostatic hypotension, tachycardia or bradycardia, fainting, prolonged QT interval, ventricular tachycardia, ventricular fibrillation and cardiac arrest. Cases of sudden death have also occurred.

Hepatobiliary disorders

Perphenazine can cause liver damage and jaundice, both reversible and chronic.

Other side effects

Other side effects that may occur following therapy with perphenazine are:

  • Dry mouth;
  • Increased salivation;
  • dizziness;
  • Hyperglycemia or hypoglycemia;
  • Glycosuria;
  • Changes in libido;
  • False positive or false negative in pregnancy tests;
  • Nasal congestion;
  • Pallor;
  • Increased sweating;
  • Skin pigmentation;
  • Peripheral edema;
  • Temperature;
  • Increased appetite and body weight;
  • Muscle weakness.


There is no specific antidote for perphenazine overdose, therefore the treatment is symptomatic and supportive.

The symptoms that can occur consist of an exacerbation of the side effects. If an excessive dose of the drug is taken, the treatment must be stopped immediately and the patient must be hospitalized.

Action mechanism

Perphenazine exerts its antipsychotic action by antagonizing D2 dopamine receptors. In fact, this monoamine is implicated in the development of psychiatric diseases.

Mode of Use - Posology

Perphenazine is available for oral administration as tablets.

The perfenazine dosage must be established by the doctor on a strictly individual basis, depending on the type and severity of the disease to be treated and according to the patient's condition.

Below are some indications on the perphenazine doses normally used. In elderly patients a reduction in the dose of the drug administered may be necessary.

In outpatients (adults and children over 12 years), the average dose of perphenazine is 8-16mg, to be taken twice a day.

In hospitalized patients, the usual drug dose is 8-32 mg, to be taken twice a day.

However, the dose of 64 mg perphenazine per day should not be exceeded.

In the treatment of uncontrollable vomiting, the usual dose of perphenazine is 8-12 mg, to be administered in divided doses during the day.

Pregnancy and breastfeeding

Due to the side effects that may occur in newborns, pregnant women should not take the drug during the first trimester of gestation. In the second and third trimester, the drug could only be used if it is indispensable and only under the strict supervision of a doctor.

Because perphenazine is excreted in breast milk, breastfeeding mothers should not take the medicine.


The use of perphenazine is contraindicated in the following cases:

  • Known hypersensitivity to perphenazine;
  • In patients in a comatose state;
  • In patients strongly depressed by alcohol or other active substances on the central nervous system;
  • In patients suffering from severe states of depression;
  • In patients suffering from bone marrow depression;
  • In patients with liver disorders;
  • In patients with suspected or ascertained subcortical brain damage;
  • In children under 12 years of age;
  • In the first trimester of pregnancy;
  • During breastfeeding.