A psychotropic drug, the purpose of which is the treatment of psychotic disorders, is called antipsychotic (also an antipsychotic or antipsychotic). What is it and how does it work? Let's figure it out.
Antipsychotic. What it is? History and Characteristics
Antipsychotics in medicine have appeared relatively recently. Before they were discovered, herbal preparations were most often used for the treatment of psychoses (for example, belena, belladonna, opiates), intravenous calcium, bromides, and narcotic sleep.
In the early 50s of the 20th century, antihistamines or lithium salts began to be used for these purposes.
One of the very first antipsychotics was chlorpromazine (or chlorpromazine), which until then was considered a common antihistamine. It began to be widely used since 1953, mainly as a sedative or as antipsychotics (for schizophrenia).
The next antipsychotic was reserpine alkaloid, but soon gave way to other, more effective drugs, since it practically did not work.
At the beginning of 1958, other first-generation antipsychotics appeared: trifluoperazin (triftazine), haloperidol, thioproperazine and others.
The term "antipsychotic" was proposed in 1967 (when the classification of first-generation psychotropic drugs was created) and it refers to drugs not only having antipsychotic effects, but also capable of causing neurological disorders (akathasia, antipsychotic parkinsonism, various dystonic reactions, and others). Typically, these disorders are caused by substances such as chlorpromazine, haloperidol and triftazine. Moreover, their treatment is almost always accompanied by unpleasant side effects: depression, anxiety, expressed fear, emotional indifference.
Previously, antipsychotics could also be called βlarge tranquilizers,β 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 partially described typical antipsychotics, now we will consider an atypical antipsychotic. What it is? This is a group of softer drugs. They do not affect the body as much as typical ones. They relate to a new generation of antipsychotics. The advantage of atypical antipsychotics is that they have a lesser effect on dopamine receptors.
Antipsychotics: indications
All antipsychotics have one basic property - an effective effect on productive symptoms (hallucinations, delusions, pseudo-hallucinations, illusions, behavior disorders, mania, aggressiveness and agitation). In addition, antipsychotics (mainly atypical) can be prescribed for the treatment of depressive or deficient symptoms (autism, emotional flattening, desocialization, etc.). However, their effectiveness in treating deficient symptoms is a big question. Experts suggest that antipsychotics can eliminate only secondary symptoms.
Atypical antipsychotics, whose mechanism of action is weaker than typical, are also used to treat bipolar disorder.
The American Psychiatric Association prohibits the use of antipsychotics to treat the psychological and behavioral symptoms of dementia. Also, they should not be used for insomnia.
It is unacceptable to be treated with two or more antipsychotic drugs simultaneously. And remember that antipsychotics are used to treat serious diseases, just taking them is not recommended.
The main effects and mechanisms of action
Modern antipsychotics have one common mechanism of antipsychotic action, because they can reduce the transmission of nerve impulses only in those brain systems in which impulses are transmitted by dopamine. Let's take a closer look at these systems and the effect of antipsychotics on them.
- Mesolimbic path. A decrease in the transmission of nerve impulses in this way occurs when taking any antipsychotic drug, since by it is meant the removal of productive symptoms (for example, hallucinations, delusions, etc.)
- Mesocortical path. Here, a decrease in impulse transmission leads to the manifestation of symptoms of schizophrenia (negative disorders such as apathy, desocialization, speech poverty, smoothing of affect, anhedonia) and cognitive impairment (attention deficit, impaired memory function, etc.) appear. The use of typical antipsychotics, especially long-term, leads to an increase in negative disorders, as well as serious impairment of brain functions. The abolition of antipsychotics in this case will not help.
- Nigrostriatal pathway. Blockade of dopamine receptors in this case usually leads to the appearance of side effects typical of antipsychotics (akathisia, parkinsonism, dystonia, salivation, dyskinesia, jaw trismus, etc.). These side effects are observed in 60% of cases.
- Tuberoinfundibular pathway (impulse transmission between the limbic system and the pituitary gland). Blocking 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 dysfunctions, infertility pathology and even a pituitary tumor.
Typical antipsychotics have a greater effect on dopamine receptors; atypical ones affect serotonin by other neurotransmitters (substances that transmit nerve impulses). Because of this, atypical antipsychotics are less likely to cause hyperprolactinemia, extrapyramidal disorders, antipsychotic depression, as well as neurocognitive deficiency and negative symptoms.
Signs of blockade of Ξ± 1 -adrenoreceptors include a decrease in blood pressure, orthostatic hypotension, dizziness, and drowsiness.
With the blockade of H 1 histamine receptors, hypotension appears, the need for carbohydrates and an increase in body weight, as well as sedation, increase.
If blockade of acetylcholine receptors occurs, the following side effects appear: constipation, dry mouth, tachycardia, urinary retention, increased intraocular pressure and disturbance of accommodation. Confusion and drowsiness are also possible.
Western researchers have proven that there is a connection between antipsychotics (new antipsychotics or old, 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 because psychotic drugs affect lipid metabolism. Reception of antipsychotics can also provoke type 2 diabetes. The chances of serious complications increase with combined treatment with typical and atypical antipsychotics.
Typical antipsychotics can provoke epileptic seizures, as they lower the threshold for convulsive readiness.
Most antipsychotics (mainly phenothiazine antipsychotics) have a large hepatotoxic effect, and can even cause the development of cholestatic jaundice.
Antipsychotic treatment in the elderly can increase the risk of pneumonia by 60%.
The cognitive effect of antipsychotics
Conducted open studies have shown that atypical antipsychotics are slightly more effective than typical in the treatment of neurocognitive deficiency. However, there is no convincing evidence of their at least some effect on neurocognitive impairment. Atypical antipsychotics, whose mechanism of action is slightly different from typical ones, are often tested.
In one clinical study, doctors compared the effects of risperidone and haloperidol in low doses. During the study, no significant differences were found in the indications. It has also been proven that haloperidol in low doses has a positive effect on neurocognitive performance.
Thus, the question of the effect of first or second generation antipsychotics on the cognitive sphere is still controversial.
Classification of Antipsychotics
It was already mentioned above that antipsychotics are divided into typical and atypical.
Among typical antipsychotics can be distinguished:
- Sedative antipsychotics (having a inhibitory effect after use): promazin, levomepromazine, chlorpromazine, alimemazine, chlorprotixen, pericyazine and others.
- Incisive antipsychotics (have potent global antipsychotic effects): fluphenazine, trifluoperazin, thioproperazine, pipothiazine, zuclopentixol, as well as haloperidol.
- Disinhibitors (have an activating, disinhibiting effect): 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 there are:
- Phenothiazines, as well as other tricyclic derivatives. Among them there are such types:
β antipsychotics with a simple aliphatic bond (levomepromazine, alimemazine, promazine, chlorpromazine), powerfully block acetylcholine receptors and adrenoreceptors, have a pronounced sedative effect and can cause extrapyramidal disorders;
β antipsychotics with a piperidine nucleus (thioridazine, pipothiazine, pericyazin), which have a moderate antipsychotic effect and mild neidocrine and extrapyramidal side effects;
β antipsychotics with piperazine nucleus (fluphenazine, prochlorperazine, perphenazine, thioproperazine, frenolone, trifluoperazin) are able to block dopamine receptors, and also weakly affect acetylcholine and adrenoreceptors.
- All derivatives of thioxanthene (chlorprotixen, flupentixol, zuclopentixol), the effect of which is similar to the action of phenothiazines.
- Substituted benzamides (tiapride, sultopride, sulpiride, amisulpride), whose action is also similar to phenothiazine antipsychotics.
- All derivatives of butyrophenone (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, dicarbin).
- Piperazinylquinolinone (aripiprazole).
Of all the above, it is possible to distinguish available antipsychotics - drugs that are sold without prescription in pharmacies, and a group of antipsychotics that are sold strictly according to the doctor's prescription.
The interaction of antipsychotics with other drugs
Like any other drugs, modern antipsychotics interact with other drugs if taken simultaneously. Some interactions are very dangerous for the human body, so it is important to know with what it is dangerous to take antipsychotics. Remember that antipsychotic poisoning often occurs precisely because of their interactions with other drugs.
Interaction with antidepressants leads to increased action of both antipsychotics and antidepressants themselves. Their combination can lead to constipation, paralytic intestinal obstruction, arterial hypertension.
It is not recommended to take together:
- The combination of antipsychotics and benzodiazepines leads to respiratory depression, sedative side effects.
- With simultaneous administration with lithium preparations, the development of hyperglycemia, the appearance of confusion, and drowsiness are possible. Their combination can be allowed, but only with medical supervision.
- The use of adrenomimetics (ephedrine, methazone, norepinephrine, adrenaline) reduces the effect of both drugs.
- Antihistamines when taken together with antipsychotics enhance their inhibitory effect on the central nervous system.
- Alcohol, drugs for anesthesia, sleeping pills or anticonvulsants, taken together with antipsychotics, have the same effect.
- Reception of antipsychotics with analgesics and anesthetics leads to an increase in their effect. This combination depresses the central nervous system.
- Antipsychotics taken with insulin and antidiabetic drugs leads to a decrease in their effectiveness.
- When taking antipsychotics with tetracyclines, the risk of liver damage by toxins increases.
Contraindications
Both atypical and typical antipsychotics have a common list of contraindications:
- individual intolerance to drugs;
- the presence of angle-closure glaucoma, prostate adenoma, porphyria, parkinsonism, pheochromocytoma;
- allergic reactions to antipsychotics in the history of man;
- violations of the liver and kidneys;
- pregnancy and lactation;
- diseases of the cardiovascular system;
- acute febrile conditions;
- coma.
Side effects of antipsychotics
With prolonged therapy, even the best antipsychotic shows side effects.
All antipsychotic drugs can increase the risk of dopamine hypersensitivity, which in turn leads to symptoms of psychosis and tardive dyskinesia.
Most often, these symptoms appear when the antipsychotic is canceled (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 antipsychotic deficiency syndrome is noted. According to unofficial data, 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, who were given olanzapine or haloperidol in normal dosage for two years, the volume and weight of the brain from taking antipsychotics decreases by an average of 8-11%. This is due to a decrease in the volume of white and gray substances. Recovery from antipsychotics is not possible.
After the publication of the results, the researchers were accused that the action of antipsychotics was not tested on animals before entering the pharmaceutical market, and that they are dangerous to humans.
One of the researchers, Nancy Andreasen, is confident that reducing the amount of gray matter and taking antipsychotics generally negatively affects the human body and leads to atrophy of the prefrontal cortex. On the other hand, she noted that antipsychotics are an important medicine that can cure many ailments, but they need to be taken only in very small quantities.
In 2010, researchers J. Leo and J. Moncrieff published a review of studies based on magnetic resonance imaging of the brain. The study was performed to compare brain changes in patients taking antipsychotics and patients who did not.
In 14 out of 26 cases (in patients taking antipsychotics), a decrease in brain volume, the volume of gray and white substances was observed.
Of 21 cases (in patients who did not take antipsychotics, or who took, but in small doses), no changes were found in any.
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 took antipsychotics for a rather long time (more than 7 years). Moreover, the larger the dose of drugs, the more significantly reduced brain volume.
New drug development
Currently, new antipsychotics are being developed that would not affect receptors. One group of researchers stated 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 that no one has any questions about what an antipsychotic is. What is it, what is its mechanism of action and the consequences of admission, we examined above. It remains only to add that no matter what the level of medicine in the modern world, no substance can be fully studied. And you can expect a trick from anything, and even more so from such complex drugs as antipsychotics.
Recently, cases of treatment of depression with antipsychotics have become more frequent. Out of ignorance of the dangers of this drug, people themselves are doing worse. In no case should antipsychotics be used for any purpose other than their direct purpose. And the effect of these drugs on the brain is out of the question.
That is why antipsychotics - drugs without prescription available for purchase, should be used with caution (and only if you are 100% sure that you need it), and even better not to use it without a doctorβs prescription.