One of the best known types of mental disorder is psychotic disorder. This type of disorder, which is considered a serious mental disorder, causes a high level of suffering to the sufferer and his or her environment.

The typical symptoms of this type of disorder, which include schizophrenia and schizoaffective disorder, can be very disabling and greatly alter the quality of life of the sufferer if left untreated. In addition, is one of the types of mental disorder with the highest level of social stigma , something that makes the situation of those who suffer from it even more difficult.

Fortunately, there are different treatments that facilitate the management and maintain the stability of patients, highlighting among them the pharmacological treatment. It is possible to find a wide variety of antipsychotic or neuroleptic drugs. One of these is perphenazine , which we will discuss 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 psychoactive substance that is highly effective 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 considerably more potent (it is estimated that up to five times more) than chlorpromazine and being especially effective in the treatment of positive symptoms (i.e. those that are added to the usual functioning of patients such as hallucinations and delusions, disorganized behavior or agitation).

Among 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 much effect on the negative symptoms (symptoms that diminish the functionality and abilities of the subject, such as abulia or thought poverty), and could even cause a worsening).

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

This does not mean that perphenazine and other typical antipsychotics are not used in clinical practice, but is not usually the first therapeutic option and is often 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 acts by blocking the dopamine D2 receptors in the brain.

It has been observed that patients with schizophrenia or other psychotic disorders often have an excess of dopamine in the mesolimbic pathway, which has been associated with positive symptoms. Thus, perphenazine blocks the dopamine receptors of this pathway at a post-synaptic level, making its activity over this region less and reducing agitation and positive symptomatology.

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

Specifically, negative symptoms (abulia, apathy, etc.) have been linked to a deficit of this substance in the mesocortical pathway, so that the action of perphenazine would not help solve this type of symptoms or could even aggravate them. This means that different side effects can appear depending on the route that suffers an unnecessary decrease in its dopamine levels, something that can alter aspects as diverse as motor, sexuality or systems as diverse as motor, sexual or sleep.

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

Main indications

The main indication for perphenazine, as an antipsychotic, is the treatment of schizophrenia . In this sense, it is especially effective in the treatment of positive symptoms such as the previously mentioned 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.

In addition, 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 in the treatment of manic episodes.

Side effects

Perphenazine is an effective and very useful drug, but like all other drugs has a large number of possible side effects of great relevance. 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 excessive 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 occur. Other possible symptoms include low blood pressure, hyperglycemia, loss of libido, and the development of galactorrhea (regardless of gender) and gynecomastia.

Mechanism of action

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

It has been observed that patients with schizophrenia or other psychotic disorders often have an excess of dopamine in the mesolimbic pathway, which has been associated with positive symptoms.
Thus, perphenazine blocks the dopamine receptors of this pathway at a post-synaptic level, making its activity over this region less and reducing agitation and positive symptomatology.

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

Another sector of the population that has contraindicated this drug is people with diabetes, since it tends to increase the level of glycemia. It is also necessary to take into account the possible interaction with other drugs and medicines, which may intensify or cancel out the effect of the drug with dangerous health outcomes. For example, is contraindicated for use with depressants such as alcohol and other drugs . Elderly people with dementia are also contraindicated, having observed that in this type of patient the probability of death increases.