The Antipsychotics Or neuroleptics are a group of drugs known for their treatment in psychoses, although they may also Applied to other diseases.
Henri Laborit, a military surgeon, carried out the necessary studies for the discovery of the first useful medicine for The pharmacological control of schizophrenia and other forms of psychosis.
Beginning in 1949, Laborit conducted pioneering research on the anesthetic use of antihistamine drugs, with the aim of reducing The shock associated with surgery.
In this way, Henri Laborit began to regularly use the antihistamines Mepiramine and Prometacin in a combined pre-anesthetic.
Subsequently, it was found that antihistamine medication also had effects on the Central Nervous System, in a way that Signs associated with the shock derived from the surgery.
In addition, he perceived certain changes in the mood of the patients to whom the drug was administered - especially in the case of Promethazine - so that people were less anxious and required a lower dose of Morphine .
In spite of these great discoveries of Laborit, the subject was in the forgetfulness during some years, until this doctor announced its Investigations Specia Laboratories .
Disorders in which antipsychotics are used
Antipsychotics are used to reassure patients who go through an acute phase of a disorder in which they present Great agitation and nervousness.
They can be used in patients with brain injury, mania, delirium due to intoxication, agitation depression or severe anxiety - in the latter case, For a short period of time.
However, the disorder for which antipsychotics have most been used is for the schizophrenia Especially to relieve the positive symptoms. It is one of the most devastating diseases in existence, in terms of personal and social cost.
It is estimated that some 20 million people in the world suffer from schizophrenia , And there were no differences in the incidence rates of the different Countries.
Most of these people who have received a diagnosis of schizophrenia have to use antipsychotics to make their lives more stable and Who have fewer periods of hospitalization.
Within the symptomatology of schizophrenia, it is important to differentiate between positive and negative symptoms:
Classification of antipsychotics or neuroleptics
We can now find two major types of antipsychotics: classical neuroleptics and atypical neuroleptics.
Classic Neuroleptics
They are antagonists of dopaminergic receptors, and their main pharmacological property is the blockade of D2 receptors, specifically in the pathway Mesolimbic.
The most common types of neuroleptics we can find are:
Haloperidol (Butiferronas). In spite of the beneficial effects that this drug has on the positive symptoms of schizophrenia, its Debilitating side effects - such as movement disorders, weight gain, lack of motivation, etc.
In some cases, it increases the likelihood of suffering from physical illnesses such as diabetes Or heart disease. Therefore, it is recommended to look for the dose Adequate to help control the symptoms of schizophrenia with the fewest possible side effects.
Chlorpromazine (Phenothiazines). It is used as a treatment for the manifestations of psychotic disorders, being clearly effective in schizophrenia and In the manic phase of manic-depressive illness. It also helps alleviate restlessness and apprehension prior to surgery. The Chlorpromazine is indicated in the control of severe nausea and vomiting and in the treatment of incoercible hypo.
Levomepromazine (Phenothiazines). It is one of the oldest antipsychotics and has a tranquilizing, anxiolytic, sedative and analgesic action. It is also A potent anesthetic enhancer. Levomepromazine possesses a potent sedative property, potentiates anesthesia with ether and hexobarbital as well Such as morphine analgesia. Side effects include drowsiness during the first few weeks of treatment.
There are also classic neuroleptics with action"retard"or depot, that allow to realize doses more spaced in the time:
Fluphenazide (Modecate).
Pipotiazide (Lonseren).
Zuclopenthixol (Cisordinol).
In the first two cases, a dose is given every 3 weeks and, in the latter case, every 2 weeks.
These classic neuroleptics are especially indicated for the treatment of:
Psychosis.
Agitation and violent behavior.
Movement disorders -tics- or Gilles de la Tourette Syndrome.
Stimulant poisoning.
Chronic pain.
Ethical deprivation.
Among its adverse effects, we can find the following:
Sedation.
Drowsiness.
Incoordination.
Convulsions.
Epileptogenic effect.
Extrapyramidal effects: dystonias, parkinsonian effects, akathisia, etc.
Orthostatic hypotension.
Mechanism of action of classical neuroleptics
These drugs are based on the Dopaminergic hypothesis , According to which the positive psychotic symptoms are related to the hyperactivity of the Dopaminergic neurons, especially the mesolimbic pathway.
Therefore, antipsychotic drugs used to treat positive symptoms act by blocking dopamine receptors, particularly Dopamine D2 receptors.
Negative symptoms of schizophrenia, described above, may involve other regions of the brain, such as the dorsolateral prefrontal cortex and Other neurotransmitters-may be related to excitatory hyperactivity of glutamate.
Atypical neuroleptics
On the other hand, we find the group of atypical neuroleptics, which are those developed more recently.
They constitute a heterogeneous group of substances that act on the positive and negative symptoms of schizophrenia - unlike neuroleptics Classic, that only act on the positives.
Some of the best known atypical antipsychotics are as follows:
Clozapine (Leponex). Derivatives of dibenzodiazepines. It is the only drug specifically indicated for the treatment of schizophrenia resistant to treatment. Certain serious clinical conditions in schizophrenia are particularly responsive to clozapine, including Persistent auditory hallucinations, violence, aggression, and suicide risk. It should also be taken into account the low incidence of Tardive dyskinesia as an adverse drug effect. It has also been shown that clozapine has a beneficial effect on the function Cognitive and affective symptoms.
Olanzapine (Zyprexa). It is also derived from benzodiazepines, and has structural and pharmacological properties similar to clozapine with a Mixed activity over multiple receptors. Although olanzapine has been shown to have antipsychotic activity, it remains to be demonstrated Its efficacy in resistant schizophrenia and its relative position with respect to other atypical antipsychotics, in which there is not too much data Conclusive. Also, the clinical relevance of the effects on the negative symptoms that are deduced from the improvement of the scales of symptoms Negative results is difficult to interpret and the more rigorous analyzes of the data fail to show a clear superiority of olanzapine. Neither Clear recommendations can be made for agitation, aggression and hostility, although it seems less sedating than chlorpromazine and Haloperidol . One of the side effects it produces is significant weight gain. For this reason, more long-term studies are needed Information on tolerance , Quality of life, social functioning, suicide, etc.
Risperidone (Risperdal). Derivative of benzoxiooxazoles. It is not yet known whether risperidone is more effective than classic neuroleptics. Seems to have Some advantages over haloperidol in terms of limited relief of some symptoms and side effects profile. May be more acceptable For patients with schizophrenia, perhaps due to the low sedation it produces, despite its tendency to increase weight. There are few Data on the clinical implications of the use of risperidone but, surprisingly, there are not in relation to the use of services, Hospitalization or community functioning. The potential clinical and side-effect benefits of risperidone Have to be weighed against the higher cost of this drug.
Quetiapine (Seroquel). It is derived from dibenzotiacipine, and it has been found that the best results achieved by this drug were obtained in the Less severe patients and their efficacy on negative symptoms was less consistent and no higher than the classic ones. Clinical trials that Have performed are all of short duration - from 3 to 8 weeks - and with a high dropout rate (48-61%). These data, coupled with the short experience Clinic of the drug, prevents conclusions can be drawn on its clinical importance.
Currently there is also an atypical neuroleptic that is being introduced, the Ziprasidone .
The data obtained so far show that it may be as effective as haloperidol for schizophrenia, although it has the drawback of Cause nausea and vomiting.
The injectable form has the added drawback of causing more pain at the site of injection than haloperidol.
Further studies are needed to compare this drug with the other atypical neuroleptics in order to draw conclusions about its efficacy real.
Although these neuropsychocytes cause less extrapyramidal effects than the classic ones, and improve the negative symptoms of schizophrenia, Have some side effects:
Tachycardia.
Dizziness.
Hypotension.
Hyperthermia.
Sialorrhea.
Leucopenia - which sometimes ends in agranulocytosis, especially because of Clozapine.
Mechanism of action of atypical neuroleptics
Serotonin-dopaminergic antagonists act as dopamine antagonists -in D2- receptors, although they also act on serotonin Especially in the 5HT2a receptors.
Classical antipsychotics against atypical antipsychotics
In schizophrenia, conventional or classic antipsychotics remain today the first choice drugs in schizophrenia.
Despite their side effects and limitations, they have been shown to be very effective in acute and maintenance treatment, Tolerated by many patients.
A further advantage of these antipsychotics is the availability of some of them in parenteral, short-term or prepared pharmaceutical forms "Depot".
However, in those cases where classical antipsychotics are not well tolerated because of their extrapyramidal effects, atypical antipsychotics Constitute an adequate alternative.
The reasons why they are still not considered top-line drugs in schizophrenia are:
Little knowledge about its safety and effectiveness in maintenance therapy.
The high cost they suppose.
Although some authors justify the use of the new antipsychotics in the"first"acute episode of schizophrenia and during illness, Based on the assumptions of a decline in relapse rates and associated morbidity and an improvement in long-term outcomes, there is no Appropriate clinical trials to assess these events.
There are also hypotheses about the advantages of atypical antipsychotics in reducing costs (shorter hospital stays, less Rehospitalizations, etc.). Although several studies with clozapine and risperidone have shown evidence of the lower cost associated with its use in Compared with the older ones, their results have been criticized for limitations in experimental design.
Due to the increase in health costs, for the selection of a drug, it is necessary to consider not only its efficacy and safety but also the cost Of the different alternatives through drug-economic studies.
This type of study is especially important in the treatment of schizophrenia, since it is a disease with a great cost for the systems Due to its early start and long course.
On the other hand, it is a disease that produces enormous personal and family suffering and a great incapacity in affected individuals. All these Support the need for adequate drug-economic studies (evaluating cost-effectiveness, cost-utility), as well as Long-term clinical trials to help define the place of the new antipsychotics in schizophrenia.
Main positive symptoms of schizophrenia
Hallucinations
It refers to the perception of some stimulus that does not exist - such as noises, voices, images, smells, etc. -.
These stimuli are perceived through sense organs, such as the ear or sight. The most common are auditory hallucinations-speakers who speak to you To the schizophrenic person or who talk to each other.
Delirious ideas
There are many types of delusions that schizophrenic people may experience, such as:
Delusion of grandeur : Belief that he possesses special powers or abilities.
Chase Delirium : The person is convinced that he constantly conspires against him or persecutes him.
Insertion of thought : The patient believes that there are thoughts that are not his, but have been introduced into his mind.
Extravagant behavior
It is common for people with schizophrenia to have unusual behaviors, such as inappropriate dressing, behavior Repetitive behavior, aggressive behavior, or inappropriate behaviors in accordance with social norms-show their genitals in public, Defecating or urinating in the street, etc.-.
Formal disorders of positive thinking
It is a fluid discourse but poor in content. Some of the disorders of thinking in schizophrenic people are:
Incoherence or schizophrenia.
Ilogicality.
Circumstantiality.
Distractibility.
Main negative symptoms associated with schizophrenia
Blunt affection
It's about a Affective flattening Which manifests itself through immutable facial expression, low visual contact, affective incongruities, etc.
Alogia
This term refers to the poverty of thought and cognition that frequently occurs in schizophrenics.
Abulia-apathy
This characteristic refers to the lack of energy or motivation, and involves numerous secondary problems, such as lack of cleanliness and hygiene, lack of Persistence at work or in the academic field, etc.
Anhedonia-unsociability
This is another characteristic that is frequently found in schizophrenic patients, and it is translated as the difficulties that the person has for Experience interest or pleasure in things.
Attention
The attention is often altered in schizophrenia, since they present difficulties to maintain the attention or to concentrate enough to End an activity.
References
- Elizondo Armendáriz, J. J. (2008). Clozapine: a historical view and current role in treatment-resistant schizophrenia.
- Gutiérrez Suela, F. (1998). Current treatment with antipsychotics of schizophrenia. Farm Hosp , 22 (4).
- Lobo, O., & De la Mata Ruiz, I. (2001). New antipsychotics. Inf Ter Sist Nac Health , 25 , 1-8.
- Peinado-Santiago, A. (2015). Efficacy of second generation neuroleptic drugs in the treatment of schizophrenia.
- Tajima, K., Fernández, H., López-Ibor, J. J., Carrasco, J.L., & Díaz-Marsá, M. (2009). Treatments for schizophrenia. Critical review on the pharmacology and mechanisms of action of antipsychotics. Psychological Records , 37 (6), 330-342.