There is a great diversity of theories and hypotheses about psychotic disorders , their causes and the way to treat them. These disorders cause great harm to those who suffer them, and produce strong distress both for the person himself and for those around him. They interfere with cognitive abilities, social relations and the emotional sphere, altering contact with reality. As these disorders limit the normative functioning of human beings, their treatment is essential .

On the basis of the research carried out, from a psychodrug perspective, several substances and active principles have been developed that can help to treat this type of problem. These are the different types of antipsychotics or neuroleptics .

Psychotic disorders

For most people, the word schizophrenia is not unfamiliar. It refers to one of the main and best known psychotic disorders, a group of disorders characterised by the presence of perceptions, ideas and behaviour that are far from the norm, normally with a certain loss of contact with reality .

This type of disorder usually involves two types of symptoms: the positive ones, which provoke or add to the usual behaviour, perception or flow of thought, and the negative ones, such as those symptoms that flatten and produce a deficit in the psycho-social-emotional state of the sufferer.

The most typical and well-known examples of the symptoms of psychotic disorders are the presence of abnormal perceptions or hallucinations and the presence of more or less structured belief systems, the so-called delusions. Although the negative symptoms are less visible, the loss of logic and coherence in thinking, poverty in language and poverty in thinking or alogia stand out.

Let us now focus on one of the forms of treatment, the pharmacological one, by reviewing the different substances used in the presence of psychotic symptoms.

Mechanism of action of neuroleptics

Drugs dedicated to fighting the symptoms of psychotic disorders are called antipsychotics or neuroleptics. Formerly known as major tranquilizers , this type of drug successfully combats typical symptoms, especially those of a positive nature.

This type of psychopharmaceutical focuses mainly on the neurotransmitter known as dopamine, due to the high level of relationship found between this hormone and psychotic symptoms .

Specifically, it has been observed that an excess of dopamine in the mesolimbic pathway causes the presence of positive symptoms such as hallucinations and delusions , while a dopaminergic deficit at the mesocortical level is the most likely cause of negative symptoms such as thought poverty and alogia. This is why the mechanism of action of drugs that treat these problems will focus on working with dopamine at the level of its synthesis, reuptake and transmission. However, among the different types of antipsychotics there are differences and nuances in the way they work, as we will see.

In addition to the treatment of psychotic disorders, some neuroleptics have been used for other types of problems, such as some motor, affective or personality disorders (e.g. borderline disorder).

Types of antipsychotics

Traditionally, antipsychotics or neuroleptics have been classified into two large groups, the classic or typical neuroleptics and the atypical ones.

1. Classic or typical antipsychotics

Discovered by chance in the 1950s, the typical antipsychotics are those with which the pharmacological treatment of psychotic disorders was initiated . This type of medication exerts its action by blocking the dopamine D2 receptors of the mesolimbic pathway, reducing the excess of this hormone in the system and causing the cessation of positive symptoms.

Within this group of antipsychotics we find some as well known as haloperidol, chlorpromazine or levomepromazine , together with others such as pimozide, zuclopenthixol or fluphenazine. They can be given either directly or as a depot, in which the substance is injected into the muscle in crystallized form so that it is slowly released over time (in cases where there is little willingness to take the medication or control of treatment follow-up).

However, despite their great usefulness, typical neuroleptics are non-specific, so that blockage of dopaminergic receptors does not occur only in the mesolimbic pathway. This leads to the alteration of other pathways that also depend on dopamine , also affecting the mesocortical pathway, from which negative symptoms seem to arise due to a deficit of dopamine. Because classical neuroleptics act by blocking their uptake, typical antipsychotics have virtually no effect on negative symptoms, and may even worsen them .

Adverse effects

In addition to this, other pathways such as nigrostriatal and tuberoinfundibular, which in psychotic disorders need not be altered in themselves, also see the uptake of dopamine inhibited, so that adverse effects may arise in the form of movement disorders such as akathisia, parkinsonian syndrome and dyskinesia , or sexual disorders such as amenorrhea or gynecomastia. These symptoms are not only uncomfortable, but can also lead to neuroleptic malignant syndrome, which could lead to death. For this reason it is necessary to carefully guide the consumption of these drugs, following the prescriptions of the professionals and being able to change the antipsychotic in order to reduce the discomfort and adverse effects.

This is why further research focused on investigating and developing other antipsychotics that would have a positive effect on negative symptoms and not produce as many side effects . This does not mean that the typical antipsychotics have stopped being used, since they are very effective and the adverse symptoms can be controlled with other medication (antiparkinsonian for motor problems, for example).

2. Atypical antipsychotics

Considering the little effect of conventional antipsychotics on negative symptoms and the high number of unwanted side effects they entail, post-psychotic research has tried to create new substances that can replace the deficiencies of this type of neuroleptic, creating safer and more effective drugs. These safer drugs have been classified as antipsychotics or atypical neuroleptics .

Within the atypical antipsychotics we find substances of various families and compositions, so depending on which one is used it will have a greater or lesser effect on various problems. The main drugs that fall into this category are clozapine, olanzapine, risperidone, sulpiride, quetiapine and ziprasidone .

Differences from classical neuroleptics

As with conventional antipsychotics, atypical antipsychotics work by blocking the dopamine D2 receptors , which in the mesolimbic pathway would have an inhibitory effect on this neurotransmitter, resulting in the cessation of positive symptoms. However, in addition to this the atypical antipsychotics have an effect on serotonin , producing also an antagonistic effect with respect to it.

It should be noted that serotonin acts as a dopamine release inhibitor. Therefore, the effect that atypical antipsychotics have on the tuber-infundibular and nigrostriatal pathways (which would be affected by a conventional neuroleptic) generates an interaction between dopamine and serotonin that would leave the dopamine level equal to or close to normal. In other words, the presence of possible adverse effects is greatly reduced .

However, since there are more serotonin receptors than dopamine receptors in the cerebral cortex, inhibiting serotonin causes an increase in dopamine release by stopping it from being released. This means that although part of its functioning blocks the release of dopamine, the fact that an inhibitor of its release is much more present and widespread makes the total level of dopamine higher. For this reason, atypical antipsychotics do have an effect on negative symptoms, by increasing the gross level of dopamine in the mesocortical pathway.

With all this, the atypical neuroleptics represent an advance that produces improvement in both positive and negative symptoms and generate a lower number of adverse effects (although they have some).

Risks and side effects of taking antipsychotics

We have briefly commented that taking antipsychotics can cause various undesirable side effects, some of which are particularly dangerous . These effects can be controlled by taking other medications or by changing the neuroleptic, and the possible effects and appearance of adverse effects after administration must be evaluated. Some of the main risks and side effects of the different types of antipsychotics are as follows.

1. Motor symptoms

One of the pathways affected secondarily by the intake of antipsychotics is nigrostriatal, which is linked to motor control.

Thus, it is common to have an extrapyramidal syndrome , in which symptoms such as parkinson$0027s tremors, the appearance of involuntary movements in tardive dyskinesia, the disappearance of spontaneous movements in akinesia or the motor restlessness of akathisia appear. These symptoms mainly occur when taking conventional or typical antipsychotics, and are not common with atypical antipsychotics.

2. Sexual symptoms

Taking certain neuroleptics may cause different sexual symptoms, generally due to the involvement of the tubero-infundibular pathway (especially in the pituitary gland). Within this type of symptoms, the cessation of menstrual flow or amenorrhea stands out, as well as galactorrhea or the emission of milk from the breasts, regardless of the sex of the patient, and gynecomastia or breast growth, also regardless of the sex of the patient. Although in general they only occur with typical antipsychotics, there are some cases with certain atypicals, such as risperidone .

3. Sedation

As we have seen, one of the original names of antipsychotics is that of major tranquilizers. This term was not given by chance , because taking antipsychotics produces a sedating effect that can be more or less powerful.

4. Neuroleptic malignant syndrome

This syndrome is one of the most serious side effects that can be caused by taking antipsychotics, which can lead to coma or even death. It is characterised by the individual suffering from tachycardia, arrhythmia, high fever, muscular rigidity and loss of consciousness a. However, it is a very rare syndrome.

5. Agranulocytosis

Described in the case of clozapine, this potential side effect is serious in causing red and white blood cell levels to get out of control. It can be lethal, so blood tests are needed as a control.

6. Other symptoms

Apart from the above symptoms, it is possible to find other problems such as weight gain, excessive salivation, tachycardia or dizziness .

Bibliographic references:

  • Azanza, J.R. (2006), Guía práctica de Farmacología del Sistema Nervioso Central. Creation and design.
  • Gómez, M. (2012). Psychobiology. Manual CEDE de Preparación PIR.12. CEDE: Madrid.
  • Salazar, M.; Peralta, C.; Pastor, J. (2011). Manual of Psychopharmacology. Madrid, Editorial Médica Panamericana.