A psychotropic drug, the purpose of which is the treatment of psychotic disorders, is called an antipsychotic (also antipsychotic or antipsychotic). What is it and how does it work? Let's find out.
Neuroleptic. What it is? History and characteristics
Neuroleptics in medicine appeared relatively recently. Prior to their discovery, the most commonly used drugs for the treatment of psychosis were herbal drugs (eg, henbane, belladonna, opiates), intravenous calcium, bromides, and narcotic sleep.
In the early 50s of the 20th century, antihistamines or lithium s alts began to be used for these purposes.
One of the very first neuroleptics was chlorpromazine (or chlorpromazine), which until then was considered a common antihistamine. It has been widely used since 1953, mainly as a sedative or as an antipsychotic (for schizophrenia).
The alkaloid reserpine became the next antipsychotic, but soon gave way to other, more effective drugs, as it had practically no effect.
Early 1958other first-generation antipsychotics appeared: trifluoperazine (triftazine), haloperidol, thioproperazine and others.
The term "neuroleptic" was proposed in 1967 (when the classification of psychotropic drugs of the first generation was created) and it referred to drugs not only having an antipsychotic effect, but also capable of causing neurological disorders (akatasia, neuroleptic parkinsonism, various dystonic reactions and other). Typically, these disorders were caused by substances such as chlorpromazine, haloperidol and triftazin. Moreover, their treatment is almost always accompanied by unpleasant side effects: depression, anxiety, severe fear, emotional indifference.
Earlier, antipsychotics could also be called "great tranquilizers", so antipsychotics and tranquilizers are one and the same. Why? Because they also cause pronounced sedative, hypnotic and tranquilizing-anti-anxiety effects, as well as a rather specific state of indifference (ataraxia). Now this name is not applied to antipsychotics.
All antipsychotics can be divided into typical and atypical. We have partially described typical antipsychotics, now we will consider an atypical antipsychotic. What it is? This is a group of softer drugs. They do not act as strongly on the body as typical ones. They belong to the new generation of neuroleptics. The advantage of atypical antipsychotics is that they have less effect on dopamine receptors.
Neuroleptics: indications
All antipsychotics have one main property - an effective effect on productive symptoms (hallucinations, delusions, pseudohallucinations, illusions, behavioral disorders, mania, aggressiveness and arousal). In addition, antipsychotics (mostly atypical) may be prescribed to treat depressive or deficient symptoms (autism, emotional flattening, desocialization, etc.). However, their effectiveness in relation to the treatment of deficient symptoms is a big question. Experts suggest that antipsychotics can only eliminate secondary symptoms.
Atypical neuroleptics, which have a weaker mechanism of action than typical ones, are also used to treat bipolar disorder.
The American Psychiatric Association prohibits the use of neuroleptics to treat the psychological and behavioral symptoms of dementia. Also, they should not be used for insomnia.
It is not acceptable to be treated with two or more antipsychotics at the same time. And remember that neuroleptics are used to treat serious diseases, it is not recommended to take them just like that.
Main effects and mechanisms of action
Modern neuroleptics have one common mechanism of antipsychotic action, because they are able to reduce the transmission of nerve impulses only in those brain systems in which dopamine transmits impulses. Let's take a closer look at these systems and the effect of antipsychotics on them.
- Mesolimbic way. A decrease in the transmission of nerve impulses in this pathway occurs when taking anyantipsychotic drug, as it means the removal of productive symptoms (for example, hallucinations, delusions, etc.)
- Mesocortical pathway. Here, a decrease in the transmission of impulses leads to the manifestation of symptoms of schizophrenia (there are such negative disorders as apathy, desocialization, poverty of speech, smoothing of affect, anhedonia) and cognitive impairment (attention deficit, impaired memory function, etc.). The use of typical neuroleptics, especially long-term use, leads to an increase in negative disorders, as well as serious impairment of brain functions. Cancellation of antipsychotics in this case will not help.
- Nigrostriatal path. The blockade of dopamine receptors in this case usually leads to the side effects typical of antipsychotics (akathisia, parkinsonism, dystonia, salivation, dyskinesia, trismus of the jaws, etc.). These side effects are observed in 60% of cases.
- Tuberoinfundibular pathway (transmission of impulses between the limbic system and the pituitary gland). Blocking the receptors leads to an increase in the hormone prolactin. Against this background, a huge number of other side effects are formed, such as gynecomastia, galactorrhea, sexual dysfunction, infertility pathology and even a pituitary tumor.
Typical neuroleptics have a greater effect on dopamine receptors; atypical ones affect serotonin with other neurotransmitters (substances that transmit nerve impulses). Because of this, atypical antipsychotics are less likely to cause hyperprolactinemia,extrapyramidal disorders, neuroleptic depression, as well as neurocognitive deficits and negative symptoms.
Signs of blockade of α1-adrenergic receptors are a decrease in blood pressure, orthostatic hypotension, the development of dizziness, the appearance of drowsiness.
With blockade of H1-histamine receptors, hypotension appears, the need for carbohydrates increases and weight gain, as well as sedation.
If blockade of acetylcholine receptors occurs, the following side effects appear: constipation, dry mouth, tachycardia, urinary retention, increased intraocular pressure and disturbances of accommodation. Confusion and drowsiness may also occur.
Western researchers have proven that there is a link between antipsychotics (new antipsychotics or old ones, typical or atypical, it doesn't matter) and sudden cardiac death.
Also, treatment with antipsychotics significantly increases the risk of stroke and myocardial infarction. This is due to the fact that psychotic drugs affect lipid metabolism. Taking antipsychotics can also trigger type 2 diabetes. The chances of getting serious complications increase with combined treatment with typical and atypical antipsychotics.
Typical antipsychotics can trigger seizures by lowering the seizure threshold.
Most antipsychotics (mainly phenothiazine antipsychotics) have a large hepatotoxic effect, and can even cause the development of cholestaticjaundice.
Antipsychotic treatment in the elderly can increase the risk of pneumonia by 60%.
Cognitive effect of antipsychotics
Open-label studies have shown that atypical antipsychotics are slightly more effective than typical antipsychotics in the treatment of neurocognitive impairment. However, there is no convincing evidence of any effect on neurocognitive impairment. Atypical antipsychotics, which have a slightly different mechanism of action than the typical ones, are tested quite frequently.
In one clinical study, physicians compared the effects of risperidone and haloperidol at low doses. During the study, no significant differences were found in the readings. Haloperidol at low doses has also been shown to have a positive effect on neurocognitive performance.
Thus, the question of the impact of first or second generation antipsychotics on the cognitive sphere is still controversial.
Classification of antipsychotics
It has already been mentioned above that antipsychotics are divided into typical and atypical.
Among typical neuroleptics are:
- Sedative antipsychotics (which have an inhibitory effect after use): promazine, levomepromazine, chlorpromazine, alimemazine, chlorprothixene, periciazine and others.
- Incisive antipsychotics (have powerful global antipsychotic effects): fluphenazine, trifluoperazine, thioproperazine, pipothiazine, zuclopenthixol, and haloperidol.
- Disinhibiting (possess activating,disinhibitory action): carbidine, sulpiride and others.
Atypical antipsychotics include substances such as aripiprazole, sertindole, ziprasidone, amisulpride, quetiapine, risperidone, olanzapine and clozapine.
There is another classification of antipsychotics, according to which they are distinguished:
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Phenotiazines, as well as other tricyclic derivatives. Among them are: ● antipsychotics with a piperidine core (thioridazine, pipotiazine, periciazine), which have a moderate antipsychotic effect and mild neudocrine and extrapyramidal side effects;
are able to block dopamine receptors, and also have little effect on acetylcholine and adrenoreceptors.
- All thioxanthene derivatives (chlorprothixene, flupentixol, zuclopenthixol) that act similarly to phenothiazines.
- Substituted benzamides (tiapride, sultopride, sulpiride, amisulpride), whose action is also similar to phenothiazine antipsychotics.
- All butyrophenone derivatives (trifluperidol, droperidol, haloperiodol, benperidol).
- Dibenzodiazapine and its derivatives (olanzapine, clozapine, quetiapine).
- Benzisoxazole and its derivatives(risperidone).
- Benzisothiazolylpiperazine and its derivatives (ziprasidone).
- Indole and its derivatives (sertindole, dicarbine).
- Piperazinylquinolinone (aripiprazole).
From all of the above, we can distinguish affordable antipsychotics - drugs sold without prescription in pharmacies, and a group of antipsychotics that are sold strictly by prescription.
Interaction of neuroleptics with other drugs
Like any other drugs, modern antipsychotics interact with other drugs if taken at the same time. Some interactions are very dangerous for the human body, so it is important to know what antipsychotics are dangerous to take with. Remember that neuroleptic poisoning often occurs precisely because of their interactions with other drugs.
Interaction with antidepressants leads to an increase in the action of both neuroleptics and the antidepressants themselves. Their combination can lead to constipation, paralytic ileus, arterial hypertension.
Not recommended to be taken together:
- Combination of antipsychotics and benzodiazepines leads to respiratory depression, sedative side effects.
- When taken simultaneously with lithium preparations, the development of hyperglycemia, the appearance of confusion, drowsiness is possible. Their combination can be allowed, but only under medical supervision.
- Use with adrenomimetics (ephedrine, metasone, norepinephrine, epinephrine) leads to a decrease in the effect of bothmedicines.
- Antihistamines, when taken together with antipsychotics, increase their inhibitory effect on the central nervous system.
- Alcohol, anesthetics, sleeping pills, or anticonvulsants combined with antipsychotics have the same effect.
- Taking antipsychotics with analgesics and anesthetics leads to an increase in their effect. This combination has a depressing effect on the central nervous system.
- Neuroleptics taken with insulin and anti-diabetic drugs lead to a decrease in their effectiveness.
- Taking antipsychotics with tetracyclines increases the risk of liver damage from toxins.
Contraindications
Both atypical and typical antipsychotics have a common list of contraindications:
- individual drug intolerance;
- presence of angle-closure glaucoma, prostate adenoma, porphyria, parkinsonism, pheochromocytoma;
- allergic reactions to antipsychotics in a person's history;
- liver and kidney disorders;
- pregnancy and breastfeeding;
- diseases of the cardiovascular system;
- acute febrile conditions;
- coma.
Side effects of antipsychotics
With long-term therapy, even the best antipsychotic has side effects.
All antipsychotic drugs can increase the risk of developing dopamine hypersensitivity, which in turn leads tosymptoms of psychosis and tardive dyskinesia.
Most often, these symptoms appear when the neuroleptic is withdrawn (this is also called "withdrawal syndrome"). The withdrawal syndrome has several varieties: hypersensitivity psychoses, unmasked dyskinesia (or recoil dyskinesia), cholinergic "recoil" syndrome, etc.
To prevent this syndrome, treatment with antipsychotics must be completed gradually, gradually reducing the dose.
When taking antipsychotics in high doses, a side effect such as neuroleptic deficient syndrome is noted. According to anecdotal evidence, this effect occurs in 80% of patients taking typical antipsychotics.
Structural changes in the brain with prolonged use
According to placebo-controlled studies of macaques given normal doses of olanzapine or haloperidol for two years, neuroleptics reduce brain volume and weight by an average of 8-11%. This is due to a decrease in the volume of white and gray matter. Recovery from antipsychotics is impossible.
After the publication of the results, researchers were accused of not testing the effects of antipsychotics on animals before entering the pharmaceutical market, and that they pose a danger to humans.
One of the researchers, Nancy Andreasen, is sure that the decrease in the volume of gray matter and the use of antipsychotics in general negatively affects the human body and leads to atrophy of the prefrontal cortex. On the other hand, she also noted that antipsychotics are an important medicine,able to cure many ailments, but should only be taken in very small amounts.
In 2010, researchers J. Leo and J. Moncrieff published a review of research based on magnetic resonance imaging of the brain. The study was carried out to compare the brain changes of patients taking antipsychotics and those not taking them.
In 14 out of 26 cases (in patients taking antipsychotics), a decrease in brain volume, gray and white matter was observed.
Of 21 cases (in patients who did not take antipsychotics, or took them, but in small doses), none showed any changes.
In 2011, the same researcher Nancy Andreasen published the results of a study in which she found changes in brain volume in 211 patients who had been taking antipsychotics for quite a long time (more than 7 years). At the same time, the larger the dose of drugs, the more significantly the volume of the brain decreased.
Drug Development
At the moment, new antipsychotics are being developed that would not affect receptors. One group of researchers claimed that cannabidiol, a component of cannabis, has an antipsychotic effect. So it is possible that soon we will see this substance on the shelves of pharmacies.
Conclusion
We hope no one has any more questions about what a neuroleptic is. What is it, what is its mechanism of action and the consequences of taking it, we discussed above. It remains only to add that whatever the level of medicine in the modern world, not a single substancecan be fully explored. And the trick can be expected from anything, and even more so from such complex drugs as antipsychotics.
Recently there has been an increase in cases of depression being treated with antipsychotics. Out of ignorance of the dangers of this drug, people make things worse for themselves. Antipsychotics should never be used for any purpose other than their intended use. And what effect these drugs have on the brain is out of the question.
This is why antipsychotics, available over the counter, should be used sparingly (and only if you're 100% sure you need them), or better yet, not used at all without a doctor's prescription.
