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Contraindications and side effects of Perphenazine

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Discover the contraindications and side effects of Perphenazine.

This medicine is used mainly to treat schizophrenia.

This medicine should always be used under medical supervision.Contraindications and side effects of Perphenazine


One of the best-known types of mental disorders is that of psychotic disorder. This type of disorder, considered a serious mental disorder, generates a high level of suffering for those who suffer from it and for those around them.

The typical symptoms of this type of disorder, among which schizophrenia and schizoaffective disorder stand out, can be very disabling and greatly alter the quality of life of those who suffer from it if they do not receive treatment.

In addition, it is one of the types of mental disorder with the highest level of social stigmatization, something that makes the situation of those who suffer from it even more difficult.

Fortunately, different treatments facilitate the management and maintain the stability of the patients, among them the pharmacological treatment.

A wide variety of antipsychotic or neuroleptic drugs can be found. One of them is perphenazine, which we are going to talk about in this article.


Perphenazine: a typical antipsychotic

Perphenazine is one of several drugs that are part of the group of antipsychotics or neuroleptics.

It is a highly effective psychoactive substance in the treatment of psychotic symptoms, which acts by reducing the level of activity of certain neurotransmitters.

It is considered a medium potency antipsychotic, being much more powerful (it is estimated that up to five times more) than chlorpromazine and is especially effective in the treatment of positive symptoms (that is, those that are added to the normal functioning of patients such as hallucinations and delusions, disorganized behavior or agitation).

Within the antipsychotics, perphenazine is classified as one of the typical or classic antipsychotics, which, although they are very useful in the treatment of the aforementioned symptoms, do not have a great effect on negative symptoms (symptoms that decrease functionality and abilities of the subject, such as abulia or poverty of thought), and could even cause an aggravation).

In addition, they can lead to the appearance of considerably annoying and disabling secondary symptoms, these two factors being elements that converged in further research towards a more favorable mechanism of action and that would lead to the generation of atypical or second-generation antipsychotics.

This is not to say that perphenazine and other typical antipsychotics are not used in clinical practice, but it is not usually the first therapeutic option and is commonly used when other drugs are not effective.

Mechanism of action

Like most antipsychotics, perphenazine’s main mechanism of action is through its action on brain dopamine. Specifically, perphenazine works by blocking dopamine D2 receptors in the brain.

And it is that it has been observed that patients with schizophrenia or other psychotic disorders usually have an excess of dopamine in the mesolimbic pathway, an excess that has been related to positive symptoms.


In this way, perphenazine blocks the dopamine receptors of this pathway at the postsynaptic level, reducing its activity in this region and reducing agitation and positive symptoms.

However, the action of perphenazine is not selective: the blockade of D2 receptors occurs not only in the mesolimbic pathway but also in other areas where dopamine levels were not altered, or even in areas where some people have a deficit of this substance.

Specifically, negative symptoms (apathy, apathy, etc.) have been linked to a deficit of this substance in the mesocortical pathway, in such a way that the action of perphenazine would not help to solve these types of symptoms or could even aggravate them.

This means that different side effects may appear depending on the pathway that suffers an unnecessary decrease in dopamine levels, something that can alter aspects as diverse as motor skills, sexuality, or systems as diverse as motor, sexual, or sleep.


In addition to the above, perphenazine also interacts with norepinephrine, histamine, serotonin, and acetylcholine.

Main indications

The main indication for perphenazine, as an antipsychotic, is for the treatment of schizophrenia.

In this sense, it is especially effective in treating positive symptoms such as the aforementioned hallucinations and delusions.

It is especially useful in those patients with a high level of agitation (since it has sedative effects) and aggressiveness. Also in catatonic patients.


Furthermore, in some cases perphenazine is used as an antiemetic, allowing the control of vomiting and nausea in patients with serious problems and constant and dangerous emission of vomit. In some cases, it can also be used to treat manic episodes.

Side effects of perphenazine

Perphenazine is an effective and highly useful drug, but like other drugs, it has a large number of possible side effects of great relevance.

And, as we have said before, perphenazine can cause different annoying side effects in different nerve pathways, which in turn can alter various body systems.

Some of the different secondary symptoms that can occur are drowsiness, the appearance of headaches, dizziness and blurred vision, dryness or excess salivation, the appearance of parkinsonian symptoms such as tremors, spasms, and involuntary movements like those of tardive dyskinesia.

Weight gain, loss of appetite, diarrhea, or constipation may also appear. Other possible symptoms are the appearance of arterial hypotension, hyperglycemia, loss of libido, and the appearance of galactorrhea (regardless of sex), and gynecomastia.

Sleep problems, despite the existence of drowsiness, are also possible, as are urinary problems (due to excess or deficiency), jaundice, and the appearance of agitation and diminished facial expression capacity.

Likewise, it is also possible that it generates an increased sensitivity to sunlight, fever, skin rashes, dark urine, leukopenia, thrombocytopenia, or priapism.

More serious symptoms can be confusion, the possible appearance of arrhythmias and bradycardias, hyperthermia, seizures, and even neuroleptic malignant syndrome (a dangerous syndrome that can lead to the death of the patient, being one of the reasons that lead to needing a control precise dosage).


Contraindications of Perphenazine

In addition to the above, it must be taken into account that some sectors of the population have contraindicated this drug, or its use should be carefully evaluated.

Among them are all those who have suffered brain injuries, liver or kidney diseases, epileptic seizures, major depression, respiratory problems, or heart or cardiovascular problems (especially in the case of a previous heart attack).

It is also contraindicated for those who have had pheochromocytoma (tumor of the adrenal medulla).

Another sector of the population that has this drug contraindicated is that of people with diabetes since it tends to increase the level of blood glucose.

It is also necessary to take into account the possible interaction with other drugs and drugs, which can intensify or cancel the effect of the drug with dangerous results for health.

For example, its use is contraindicated against depressant substances such as alcohol and other drugs.

Elderly people with dementia also have it contraindicated, having observed that in this type of patient the probability of death increases.


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