Antipsychotics (neuroleptics) are used not only in the treatment of various psychoses. They can also be given to patients suffering from some forms of depression. It is a very heterogeneous group of drugs because they interact with different strengths on different types of receptors in the nervous system.
Antipsychoticswere discovered essentially by accident. The first of them - chlorpromazine - was originally intended as an anesthetic (anesthetic). In the 1950s, however, it was discovered that this preparation also has a calming effect, and it was then that chlorpromazine began to be used in patients with psychiatric diseases. The doctors who first used the drug to treat mental he alth problems were two French: Jean Delay and Pierre Deniker.
The term "neuroleptics" is derived from two Greek words: the first is neuro, meaning "nerve", and the second lepsis, meaning "attack / seizure".
Currently, chlorpromazine is rarely used anymore. In addition to it, other antipsychotic preparations are used, with less characteristic side effects and much greater ease of use.
Types of antipsychotic drugs
Pharmacologists divide antipsychotics into two groups. There areclassical (1st generation) neurolepticsandatypical (2nd generation) neuroleptics .
The classic antipsychotic drugs include :
- chlorpromazine,
- haloperidol,
- droperidol,
- pimozide,
- levpromazine,
- promethazine,
- thioridazine,
- sulpiryd.
These agents have a tendency to cause typical side effects of neuroleptics, which are the so-calledextrapyramidal symptoms(muscle stiffness, slowness, tremors, walking problems).
Preparations that are better tolerated by patients and less often lead to the aforementioned ailments, on the other hand, are newer antipsychotics, i.e. atypical neuroleptics. These include, first of all, the following drugs:
- aripiprazole,
- amisulpryd,
- clozapine,
- quetiapine,
- olanzapine,
- risperidon,
- sertindole,
- ziprasidon,
- zolepina.
Antipsychotic drugs can also be divided according to the way they can be administered. Neuroleptics are available in the form oforallypreparations (e.g. tablets or solutions), andintramuscular injections . The latter are sometimes of particular interest to patients, as long-acting drugs (the so-calleddepot ) can be administered by injection. However, this form of drug therapy has both advantages and disadvantages. The advantages of long-acting (depot) neuroleptics include the fact that, thanks to the use of antipsychotic drugs in the form of a depot, it is possible to obtain a constant amount of the drug in the body. The disadvantages of such therapy include the requirement to regularly visit a doctor at scheduled times in order to administer subsequent doses of neuroleptics.
Effects of antipsychotic drugs
The general mechanism of action of all neuroleptics is one: these drugs block dopaminergic D2 receptors in the central nervous system. This action is beneficial, inter alia, if there are productive symptoms in the patient, which occur as a result of an excess of dopamine in the structures of the so-called the mesolimbic system. Classic neuroleptics block D2 receptors in this system, as well as in other regions of the brain - blocking the activity of these structures in places such as the mesocortical pathway leads to the occurrence of side effects of neuroleptics, such as extrapyramidal symptoms.
The atypical preparations work a bit differently - they are more specific. They mainly affect those D2 receptors that exist in the structures of the mesolimbic system. Antipsychotic drugs affect not only the above-mentioned receptors - their action also includes modifying the activity of some serotonin, adrenergic, cholinergic and histaminergic receptors. However, atypical neuroleptics primarily have an effect on serotonin receptors. This information is important primarily because, thanks to the blocking of 5-HT2A serotonin receptors, the areas of the brain regulating motor activities (e.g. in the nigrostriatal pathway) increase in dopaminergic activity - thanks to this, atypical preparations have much lower levels of activity. than classic drugs, it tends to generate extrapyramidal symptoms in patients.
Antipsychotics: indications for the use of neuroleptics
As their name suggests, antipsychotic drugs are primarily used in peoplepatients with various psychoses. Neuroleptics can be used both to treat patients with hallucinations and to treat patients experiencing delusions. The main indications for therapy with antipsychotics are:
- various forms of schizophrenia (neuroleptics are used both in the acute phase of these diseases and in chronic maintenance therapy to prevent episodes of psychosis),
- bipolar disorder (especially in the case of manic episodes and mixed episodes),
- psychotic depression,
- schizoaffective disorder.
Neuroleptics are also used in patients with depression - however, they are turned on only when other drugs fail to control the disease and then they constitute an additional, not the basic, method of treatment. Antipsychotic drugs can also be used in patients with nervous tics. Neuroleptics, due to the fact that they also have a calming and sedative effect, are sometimes used in the case of insomnia, anxiety disorders and in patients with various dementia - however, they are only used when other treatment options fail.
Antipsychotics: contraindications
There are rather few conditions in which all neuroleptics would be contraindicated. This is due to the fact that there are many different antipsychotic drugs and practically each of them may work in a slightly different way (this is due to the different effect of individual neuroleptics on different receptors).
The only exception to this rule are patients who are poisoned by substances depressing the nervous system, such as alcohol or narcotic analgesics - neuroleptics should not be used in them. There are also many problems, the existence of which necessitates the careful selection of an antipsychotic drug - the agent must be safe for a given patient.
The contraindications for the use of antipsychotic drugs include:
- Parkinson's disease, history of the neuroleptic malignant syndrome and breast cancer associated with hyperprolactinaemia (people with these conditions should not use classic neuroleptics, but atypical drugs are available),
- agranulocytosis,
- prostate hypertrophy,
- angle-closure glaucoma,
- myasthenia gravis,
- adrenal insufficiency,
- cardiovascular diseases,
- epilepsy,
- liver dysfunction,
- kidney damage,
- hypothyroidism
Even if a patienthas any of the above-mentioned problems, it is still possible for him to use neuroleptics, but not any of them. For example, in a patient who has had an episode of agranulocytosis, clozapine should not be used - this neuroleptic has among its side effects causing this hematological disorder.
Antipsychotics: side effects of neuroleptics
Neuroleptics can cause a wide variety of side effects. The following are a collection of different conditions that can generally arise from the use of antipsychotic drugs - it is not the case that every neuroleptic can cause all of the following side effects. Namely, they depend on which specific receptors are affected by a given drug. For example, drugs that block adrenergic receptors can cause a drop in blood pressure, while other drugs that block histamine receptors can cause, for example, significant drowsiness. Possible side effects during neuroleptic therapy may be:
- fatigue,
- sedation (in the form of severe sleepiness and decreased overall activity level),
- memory impairment,
- extrapyramidal symptoms,
- skin rashes,
- skin hypersensitivity to sunlight,
- weight gain,
- metabolic disorders (e.g. impaired glucose tolerance),
- orthostatic hypotension (drops in blood pressure associated with standing),
- libido disorders (both its increase and decrease),
- Neuroleptic Malignant Syndrome,
- potency disorders,
- hyperprolactinemia and its consequences (this is a side effect mainly of classic neuroleptics, in men it can lead to e.g. gynecomastia, in women it can cause, for example, menstrual disorders),
- dry mouth,
- headaches,
- diarrhea,
- constipation,
- drooling,
- dizziness,
- heart rhythm disturbance.
The side effects of neuroleptics in the form of extrapyramidal symptoms and the neuroleptic malignant syndrome require more information.
Extrapyramidal symptomsare among the most common side effects of neuroleptics. They appear as a result of non-selective blocking of dopaminergic receptors in the brain and mainly concern patients using classic neuroleptics (atypical preparations may also - especially after prolonged use - lead to extrapyramidal symptoms, however, they havedefinitely less likely to do so). The history of extrapyramidal symptoms is quite interesting, because in the initial period of using neuroleptics it was believed that they appeared when the patient was given the appropriate dose of the neuroleptic. Even a gradual increase in the dose of antipsychotic drugs was undertaken until the patient experienced extrapyramidal symptoms. Nowadays, these ailments are definitely considered a side effect of the use of neuroleptics.
The extrapyramidal symptoms are various types of involuntary movements, such as:
- dystonias (compulsion to twist and bend different parts of the body),
- early and late dyskinesia (uncoordinated movements),
- muscle tremors,
- akathisia (motor agitation and compulsion to be in constant motion).
In addition to those listed, the extrapyramidal symptoms also include bradykinesia (slowing down of movement) and an increase in muscle tone.
The most common side effect of neuroleptics has been described above, and the most dangerous of them, theneuroleptic malignant syndrome , should be mentioned. Statistically, it occurs in less than 1% of patients taking antipsychotic drugs, but it should be mentioned because the occurrence of neuroleptic malignant syndrome requires immediate discontinuation of neuroleptics and treatment in a hospital setting. The pathogenesis of this unit takes into account sudden changes in dopamine concentration within the brain, and the symptoms of the neuroleptic malignant syndrome may be:
- disturbance of consciousness (even in the form of coma),
- tachycardia,
- increase in blood pressure,
- sweating,
- extremely significant increase in muscle tone,
- significant increase in body temperature,
- pale skin,
- laboratory abnormalities (e.g. leukocytosis, increase in creatine phosphatase or aminotransferases).
Neuroleptic Malignant Syndrome is considered to be the most dangerous side effect of neuroleptic therapy because, if untreated, the risk of dying from it is even 20%.
Antipsychotics: neuroleptics and pregnancy
Antipsychotic drugs should be avoided in pregnant women unless absolutely necessary. However, if the patient, due to her mental state, requires therapy with neuroleptics, the choice of a specific drug should be made with particular care.
Among the antipsychotic preparations, there are those that are classified as category D according to the FDA (i.e. drugs,with evidence that they may have adverse effects on the fetus) - such a drug is, for example, zolepine.
There are also safer agents, classified as category B according to the FDA (category B means that animal studies have not detected any threats to their fetuses, no studies have been carried out on humans so far) - an example of a neuroleptic classified in this category is clozapine .
Antipsychotics: neuroleptics and their use in children
Neuroleptics in children can be used, but they are definitely not first-line drugs in this age group. Before the treatment of children with antipsychotics is started, attempts are made to treat them with other drugs - only when they fail to improve the child's mental state, is it possible to consider giving him neuroleptics.
Antipsychotics: can one get addicted to neuroleptics?
Antipsychotic preparations do not exert a narcotic effect on the central nervous system, so there is no risk that the patient using them may become addicted to them. It is worth noting, however, that while taking them, alcohol or drugs have an increased effect on the body of the treated person - therefore, neuroleptics should definitely not be combined with the above-mentioned substances.