Typical and Atypical Antipsychotics: Types and How They Act

The antipsychotics or neuroleptics are a group of known treatment in psychosis drugs, but can also  be applied to other diseases.

Henri Laborit, a military surgeon, was the one who carried out the necessary studies to produce the discovery of the first drug useful for  the pharmacological control of schizophrenia and other forms of psychosis.


From the year 1949, Laborit carried out 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 Mepyramine and Promethazine in a pre-anesthetic combination.

Subsequently, he found that the antihistamine medication also exerted effects on the Central Nervous System, in a way that helped to limit the  signs associated with the shock derived from the surgery.

Typical and Atypical Antipsychotics

In addition, he noticed certain changes in the state of humor of the patients who were given the medication -especially in the case of  Promethazine-, so that people were less anxious and required a lower dose of Morphine.

Despite these great discoveries of Laborit, the matter was forgotten for some years, until this doctor disclosed his  research to Specia Laboratories .

Disorders in which antipsychotics are used

Antipsychotics are used to reassure patients who go through an acute phase of some disorder in which they have  great agitation and nervousness.

They can be used in patients with brain injury, mania, delirium due to intoxication, depression with agitation or serious anxiety -in the latter case,  for a short period of time-.

However, the disorder for which most antipsychotics have been used is for schizophrenia-especially to alleviate positive symptoms-. It is one of the most devastating diseases that exist, in terms of personal and social cost.

It is estimated that some 20 million people in the world suffer from schizophrenia, there being no differences in the percentages of incidence 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  have fewer periods of hospitalization.

Within the symptomatology of schizophrenia, it is important to differentiate positive and negative symptoms:

Classification of antipsychotics or neuroleptics

Currently we can find two major types of antipsychotics: the classic neuroleptics and the atypical neuroleptics.

Classical neuroleptics

They are antagonists of dopaminergic receptors, and their main pharmacological property is the blockade of D2 receptors, specifically in the  mesolimbic pathway.

The most common types of classic neuroleptics we can find are:

  • Haloperidol  (Butiferronas). Despite 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.- must be weighed  .

In some cases, it increases the likelihood of suffering from physical illnesses such as diabetes or heart disease. Therefore, it is recommended to find the appropriate dose  to help control the symptoms of schizophrenia with the least 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 intractable hiccups.

  • 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 has a powerful sedative property, potentiates anesthesia with ether and hexobarbital as well  as morphine analgesia. Among its side effects is the drowsiness produced during the first weeks of treatment.

There are also classic neuroleptics with “retard” or depot action, which allow for more spaced doses over time:

  • Flufenazide (Modecate).

  • Pipotiazide (Lonseren).

  • Zuclopenthixol (Cisordinol).

In the first two cases, a dose is administered 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.

  • Intoxication by stimulants.

  • Chronic pain.

  • Alcoholic 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 positive psychotic symptoms are related to the hyperactivity of  dopaminergic neurons, especially the mesolimbic pathway.

Therefore, antipsychotic drugs used to treat positive symptoms act by blocking dopamine receptors, particularly  dopamine D2 receptors.

The negative symptoms of schizophrenia, described above, may involve other regions of the brain, such as the dorsolateral prefrontal cortex and  other neurotransmitters – it may be related to the 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 classic neuroleptics  , which only act on the positive ones.

Some of the best known atypical antipsychotics are the following:

  • Clozapine  (Leponex). Derivatives of dibenzodiazepines. It is the only drug indicated specifically for the treatment of treatment-resistant schizophrenia  . Certain serious clinical conditions in schizophrenia are particularly responsive to clozapine, including  persistent auditory hallucinations, violence, aggressiveness and the risk of suicide. Likewise, the low incidence of tardive dyskinesia should be taken into account  as an adverse effect of the drug. It has also been shown that clozapine has a beneficial effect on cognitive function  and affective symptoms.

  • Olanzapine  (Zyprexa). It is also derived from dibenzodiazepines, and has structural and pharmacological properties similar to clozapine with a  mixed activity on multiple receptors. Although it has been shown that olanzapine has an antipsychotic activity, its efficacy in resistant schizophrenia and its relative position with respect to other atypical antipsychotics, in which there is not too conclusive data  , has yet to be demonstrated  . Likewise, the clinical relevance of the effects on the negative symptoms that are deduced from the improvement of the scales of negative symptoms  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, aggressiveness and hostility, although it seems less sedative than chlorpromazine and  haloperidol. One of the side effects that it produces is the significant increase in weight. For all these reasons, more long-term studies that show data on tolerance , quality of life, social functioning, suicide, etc. are needed  .

  • Risperidone (Risperdal). Derived from benzoxiooxazoles. It is not yet known if risperidone is more effective than classical neuroleptics. It seems that it has  some advantages over haloperidol in terms of the limited relief of some symptoms and the profile of side effects. It may be more acceptable  for patients with schizophrenia, perhaps due to the low sedation it produces, despite its tendency to increase weight. There is little  data on the clinical implications of the use of rysperidone but, surprisingly, there are no data regarding the use of services,  hospitalization or functioning in the community. The potential clinical benefits and reduction of side effects of risperidone they have to be weighed against the higher cost of this drug.

  • Quetiapine  (Seroquel) It is derived from dibenzothiacipin, and it has been found that the best results achieved by this drug were obtained in  less severe patients and its efficacy on negative symptoms was less consistent and not superior to the classic ones. The clinical trials that have  been carried out are all of short duration – from 3 to 8 weeks – and with a high dropout rate (48-61%). These data, together with the short clinical experience  of the drug, prevents conclusions about its clinical importance.

Currently there is also an atypical neuroleptic that is being introduced, Ziprasidone.

The data obtained so far show that it can be as effective as haloperidol for schizophrenia, although it has the disadvantage of  causing nausea and vomiting.

The injectable form has the added drawback of causing more pain at the injection site than haloperidol.

It is still necessary to carry out more studies comparing this drug with the other atypical neuroleptics in order to draw conclusions about its real efficacy  .

Although these neuropsychotics cause less extrapyramidal effects than the classic ones, and they improve the negative symptoms of schizophrenia, they also  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

The serotonin-dopaminergic antagonists act as antagonists of dopamine -in D2 receptors-, but also act on serotonin  -especially in 5HT2a receptors-.

Classical antipsychotics versus atypical antipsychotics

In schizophrenia, conventional or classic antipsychotics remain today the drugs of first choice in schizophrenia.

Despite its side effects and limitations, it has been shown to be very effective in acute treatment and maintenance, being well  tolerated by many patients.

An additional advantage of these antipsychotics is the availability of some of them in parenteral dosage forms, of short duration or “depot” preparations  .

However, in those cases in which classical antipsychotics are not well tolerated due to their extrapyramidal effects, atypical antipsychotics  are an adequate alternative.

The reasons why they are not considered first-line drugs in schizophrenia are:

  • Little knowledge about its safety and efficacy in maintenance therapy.

  • The high cost involved.

Although some authors justify the use of the new antipsychotics in the “first” acute episode of schizophrenia and during the disease,  based on the hypothesis of a decrease in relapse rates and associated morbidity and an improvement in the long-term results, there are no  adequate clinical trials that assess these facts.

There are also hypotheses about the advantages of atypical antipsychotics in reducing costs (shorter hospital stays, fewer  rehospitalizations, etc.). Although several studies with clozapine and risperidone have shown evidence of the lower cost associated with their use  compared to older ones, their results have been criticized for limitations in the experimental design.

Due to the increase in healthcare expenses, 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 pharmacoeconomic studies.

This type of studies is especially important in the treatment of schizophrenia, since it is a disease with a high cost for health systems  due to its early onset and long course.

On the other hand, it is a disease that produces an enormous personal and family suffering and a great incapacity in the affected individuals. All these  facts support the need to carry out adequate pharmacoeconomic studies (evaluating the cost-effectiveness, cost-utility ratio), as well as  long-term clinical trials to help define the place of the new antipsychotics in schizophrenia.

Main positive symptoms of schizophrenia


It refers to the perception of some stimulus that does not exist -such as noise, voices, images, smells, etc.-.

These stimuli are perceived through sensory organs, such as hearing or sight. The most common are auditory hallucinations-voices that speak  to the schizophrenic person or talk to each other.

Delirious ideas

There are many types of delusions that schizophrenic people can experience, such as:

  • Delirium of grandeur : belief that possesses special powers or abilities.

  • Delusion of persecution : the person is convinced that constantly conspires against him or persecute 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 among people who have schizophrenia to exhibit unusual behaviors, such as dressing inappropriately, carrying out repetitive behavior  , behaving aggressively or behaving inappropriately according to social norms – showing 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 thinking disorders in schizophrenic people are:

  • Incoherence or schizoafiasia.

  • Ilogicality

  • Cincuentancialidad.

  • Distrability

Main negative symptoms associated with schizophrenia

Dull affect

It is an affective flattening that manifests itself through an immutable facial expression, scarce eye contact, affective incongruities, etc.


This term refers to the poverty of thought and cognition that frequently occurs in schizophrenics.


This characteristic refers to the lack of energy or motivation, and involves many secondary problems, such as lack of cleanliness and hygiene, lack of  persistence at work or in the academic environment, etc.


This is another feature that is frequently found in schizophrenic patients, and is translated as the difficulties that the person has to  experience interest or pleasure in things.

Also Read: What is Brief Therapy Focused on Solutions?


The attention is usually altered in schizophrenia, since they have difficulties in maintaining attention or concentrating enough to  finish an activity.

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