New generation antipsychotics without side effects. Antipsychotics - a list of drugs of all groups and the safest drugs

One of the drugs used in psychiatry are neuroleptics. These funds are prescribed to people who have mental, psychological, neurological disorders. Such diseases are accompanied by aggression, phobia, hallucinations. Clearly, the manifestation of schizophrenia can be viewed from the archives of clinics.

Is there a cure for schizophrenia

To identify symptoms in schizophrenics, there are psychological tests. The most popular is the Luscher test, which is presented as a color table. In the process of choosing certain colors, a certain picture is drawn up and a competent specialist is able to reliably decipher it.

The main action of sedative neuroleptics is to remove the reaction to stimuli, neutralize:

• hallucinations;
• Sense of anxiety;
• aggression;
• paranoia;
• An unreasonable state of anxiety.

A large group of these drugs are divided into sedatives and antipsychomatics. Antipsychotics are used primarily to treat schizophrenia. Such drugs reduce psychotic. Antipsychotics are also divided into typical and atypical types.

Typical are antipsychotics with a powerful therapeutic effect.

They have a good antipsychotic effect. The list of side effects in the elderly is negligible or non-existent.

How to cure schizophrenia

Schizophrenia is a chronic illness leading to a personality disorder. People aged 16-25 can get sick with schizophrenia. Occasionally, the disease manifested itself in children as young as 5 years of age and in people over 45 years of age.

The progressive stage of schizophrenia is characterized by:

• Associative behavior;
• auditory hallucinations;
• References;
• Closure in yourself.

As a rule, patients with schizophrenia are not prone to aggression. Only the use of psychoactive substances (alcohol, drugs) can stimulate the manifestation of violence. Schizophrenia can be caused by acute stress. But this is not the only case of the disease. Any disease of the body can provoke its development.

Therefore, schizophrenia is treated by managing the symptoms.

There is no single answer to the question of whether schizophrenia can be cured completely and forever. Many scientists are fighting for the answer that the disease is curable. But there is confidence that modern methods make it possible to maintain the quality of life. A large number of clinics in Moscow, Novosibirsk, Rostov-on-Don and other cities are engaged in the study of schizophrenia.

Fundamentals of Schizophrenia Treatment

Every year, new generation drugs appear in the arsenal of doctors. The main part of therapy is the selection of medications. Drugs such as nootropics are used to stimulate the brain, increase cognitive abilities. Below is a list of neuropleeptics recommended by leading experts.

Feedback on them is also positive.

1. Azaleptin. Clozapine is the active ingredient. Does not develop catalepsy, oppression of behavior. In clinical conditions, Azaleptin has a rapid sedative effect. The medicine is well tolerated by patients. The cost is about 200 rubles.
2. galloper- antipsychotic, neuroleptic, antiemetic. With the utmost care, appoint patients with cardiovascular pathology, a predisposition to glaucoma, functional disorders of the liver, and who experience epileptic seizures. The price, depending on the form of release, varies from 50 to 300 rubles.
3. Zyprexa zidis round tablets, yellow. A drug that affects a number of receptor systems. Price from 4000 rubles.
4. Clopixol-Akufaz- injection. It is used for the initial stage of treatment of acute mental, chronic psychosis (exacerbation). The cost of the drug is 2000–2300 rubles.
5. Senorm- drops for oral administration. The active substance is haloperidol. The cost is about 300 rubles.
6. Propazine- tablets, coated with a blue color with splashes and marbling. It has less pronounced side effects. The price is about 150 rubles.
7. Triftazin, solution in ampoules 0.2%. The active substance is trifluoperazine. Blocks dopamine receptors in different brain structures. Compatible with other antipsychotics, tranquilizers and antidepressants. The cost of 10 pieces in a package is 50-100 rubles.
8. Chlorprothixene 50 . Analgesic, antidepressant, antipsychotic, antiemetic, sedative. The average price is 350 rubles.

Schizophrenia is accompanied by a mood disorder. To bring the patient out of this state, normotimics are used. Unlike neuroleptics prescribed for mania, normothymic drugs are used for bipolar affective disorder.

Can schizophrenia be cured?

For thirty years, the domestic drug Phenazepam has not lost its significance. This is due to the effectiveness of its properties, which are better realized depending on the dose used and the treatment with hypnosis. There is such a method of treatment as cytokine therapy. Cytokines are protein molecules that carry signals from one cell to another, thereby ensuring the coherence of the actions of the immune system, the processes of restoration of various organs, including the brain.

Together with medications, psychological therapy is prescribed. In this case, the doctor selects an approach to the patient at the psychological level, conducts treatment through communication.

It is important to involve family in the process of healing the patient. Such treatment makes it possible to induce certain behaviors in the patient, which will help determine the probable causes of the disease. With the help of cognitive-behavioral psychotherapy, the patient is aware of the symptoms of the disease and strengthens control over them. Most patients can lead a productive life. For such people, occupational therapy programs have been created that act as a recovery for the sick.

Gives a relaxing effect tincture of:

• Chamomile;
• Flowers of prickly hawthorn;
• corollas of motherwort;
• Dried herbs.

Treatment with folk remedies may seem impossible, but there are ways. In the fight against schizophrenia, viburnum bark helps. Don't forget about exercise. Running will help get rid of obsessive ideas of hallucinations.

List of non-prescription antipsychotic drugs

In some cases, with the possible development of serious complications, insulin shock therapy is used. The essence of this method is to place the patient in a coma. Modern supporters of insulin-comatose therapy recommend its forced course, which includes approximately 20 com. First of all, schizophrenia is treated with antipsychotics. Finding such drugs that are dispensed without a doctor's prescription is quite difficult.

But still, there is a small list:

• Etaperazine;
• paliperidone;
• Chlorprothixene.

Etaperzine - available in the form of tablets, has an inhibitory effect on the nervous system. The average cost of the drug is 350 rubles. Paliperidone is effective in the treatment of schizophrenia, schizoaffective disorder, and bipolar disorder. Price from 13 thousand rubles. Chlorprothixene - the drug has a pronounced antipsychotic and sedative effect, enhances the effect of hypnotics and analgesics. The average cost is 200 rubles.

Attack of schizophrenia (video)

In conclusion, it is worth noting that neuroleptics are aimed at suppressing these manifestations. Atypical antipsychotics are a fairly new group of drugs, their effectiveness is not much different from typical ones.

Antipsychotics include drugs intended for the treatment of psychosis and other severe mental disorders. The group of antipsychotic drugs includes a number of phenothiazine derivatives (chlorpromazine, etc.), butyrophenones (haloperidol, droperidol, etc.), diphenylbutylpiperidine derivatives (fluspirilene, etc.), etc.
Antipsychotics have a multifaceted effect on the body. Their main pharmacological features include a kind of calming effect, accompanied by a decrease in reactions to external stimuli, a weakening of psychomotor arousal and affective tension, suppression of fear, and a decrease in aggressiveness. They are able to suppress delusions, hallucinations, automatism and other psychopathological syndromes and have a therapeutic effect in patients with schizophrenia and other mental illnesses.
Antipsychotics in normal doses do not have a pronounced hypnotic effect, but they can cause a drowsy state, promote the onset of sleep and enhance the effect of hypnotics and other sedatives (sedatives). They potentiate the action of drugs, analgesics, local anesthetics and weaken the effects of psychostimulant drugs.
In some antipsychotics, the antipsychotic effect is accompanied by a sedative effect (aliphatic phenothiazine derivatives: chlorpromazine, promazine, levomepromazine, etc.), while in others (phenothiazine piperazine derivatives: prochlorperazine, trifluoperazine, etc.; some butyrophenones) - activating (energizing). Some neuroleptics relieve depression.
In the physiological mechanisms of the central action of neuroleptics, the inhibition of the reticular formation of the brain and the weakening of its activating effect on the cerebral cortex are essential. A variety of effects of neuroleptics are also associated with the impact on the occurrence and conduction of excitation in different parts of the central and peripheral nervous system.
Antipsychotics change neurochemical (mediator) processes in the brain: dopaminergic, adrenergic, serotonergic, GABAergic, cholinergic, neuropeptide and others. Different groups of antipsychotics and individual drugs differ in their effect on the formation, accumulation, release and metabolism of neurotransmitters and their interaction with receptors in different brain structures, which significantly affects their therapeutic and pharmacological properties.
Antipsychotics of different groups (phenothiazines, butyrophenones, etc.) block dopamine (D2) receptors in different brain structures. It is believed that this causes mainly antipsychotic activity, while the inhibition of central noradrenergic receptors (in particular, in the reticular formation) is only sedative. Not only the antipsychotic effect of neuroleptics, but also the neuroleptic syndrome caused by them (extrapyramidal disorders), explained by the blockade of dopaminergic structures of the subcortical formations of the brain (substance nigra and striatum, tuberous, interlimbic and mesocortical regions), where significant number of dopamine receptors.
Influence on central dopamine receptors leads to some endocrine disorders caused by antipsychotics. By blocking the dopamine receptors of the pituitary gland, they increase the secretion of prolactin and stimulate lactation, and acting on the hypothalamus, they inhibit the secretion of corticotropin and growth hormone.
Clozapine, a derivative of piperazino-dibenzodiazepine, is a neuroleptic with pronounced antipsychotic activity, but practically no extrapyramidal side effects. This feature of the drug is associated with its anticholinergic properties.
Most antipsychotics are well absorbed by various routes of administration (orally, intramuscularly), penetrate through the BBB, but accumulate in the brain in much smaller amounts than in the internal organs (liver, lungs), metabolized in the liver and excreted in the urine, partly in the intestines. They have a relatively short half-life and after a single application, they act for a short time. Prolonged drugs (fluphenazine, etc.) have been created that have a long-lasting effect when administered parenterally or orally.

They have a side effect due to their influence on the level of dopamine in the brain (decrease, which leads to the phenomena of drug-induced parkinsonism (extrapyramidal symptoms). In patients, muscle stiffness, tremor phenomena of varying severity, hypersalivation, the appearance of oral hyperkinesis, torsion spasm are noted etc. In this regard, in the treatment of neuroleptics, such correctors as cyclodol, artan, PK-Merz, etc. are additionally prescribed.

Aminazine (chlorpromazine, largactil) - the first antipsychotic drug, gives a general antipsychotic effect, is able to stop and (hallucinatory-), as well as manic and to a lesser extent. With prolonged use, it can cause parkinson-like disorders. The strength of the antipsychotic action of chlorpromazine in the conditional scale for evaluating neuroleptics is taken as one point (1.0). This allows you to compare it with other antipsychotics (Table 4).

Table 4. List of Antipsychotics

Neuroleptic	Aminazine coefficient	Daily dose in hospital, mg
Aminazin	1,0	200-1000
Tizercin	1,5	100-500
Leponex	2,0	100-900
Melleril	1,5	50-600
Truxal	2,0	30-500
Neuleptyl	1,5	100-300
Clopixol	4,5	25-150
Seroquel	1,0	75-750
Etaperazine	6,0	20-100
Triftazin	10,0	10-100
Haloperidol	30,0	6-100
Fluanxol	20,0	3-18
Olanzapine	30,0	5-20
Ziprasidone (Zeldox)	2,0	80-160
Rispolept	75,0	2-8
moditen	35,0	2-20
Pipothiazine	7,0	30 — 120
Mazeptil	15,0	5-60
Eglonil	0,5	400-2000
Amisulpiride (solian)	1,0	150-800

Propazine is a drug obtained to eliminate the depressive effect of chlorpromazine by eliminating the chlorine atom from the phenothiazine molecule. It gives a sedative and anti-anxiety effect in case of neurotic and x, presence. Does not cause pronounced phenomena of parkinsonism, does not have an effective effect on and.

Tizercin (levomepromazine) has a more pronounced anti-anxiety effect compared to chlorpromazine, is used to treat affectively, in small doses it has a hypnotic effect in the treatment of neuroses.

The described drugs belong to aliphatic derivatives of phenothiazine, are available in tablets of 25, 50, 100 mg, as well as in ampoules for intramuscular injection. The maximum dose for oral administration is 300 mg / day.

Teralen (alimemazine) was synthesized later than other aliphatic phenothiazine antipsychotics. Currently produced in Russia under the name "teraligen". It has a very mild sedative effect, combined with a slight activating effect. Stops the manifestations of the vegetative psychosyndrome, fears, anxiety, hypochondriacal and senestopathic disorders of the neurotic register, is indicated for sleep disorders and allergic manifestations. On and unlike chlorpromazine does not work.

Atypical antipsychotics (atypicals)

Sulpiride (egloil) is the first atypical drug synthesized in 1968. It does not have pronounced side effects of action, it is widely used for the treatment of hypochondriacal, senestopathic syndromes, it has an activating effect of action.

Solian (amisulpiride) is similar in action to eglonil, is indicated both for the treatment of conditions with hypobulia, apathetic manifestations, and for the relief of hallucinatory-delusional disorders.

Clozapine (leponex, azaleptin) does not have extrapyramidal side effects, it exhibits a pronounced sedative effect, but unlike chlorpromazine, it is not indicated for the treatment of hallucinatory-delusional and catatonic syndromes. Complications in the form of agranulocytosis are known.

Olanzapine (Zyprexa) is used to treat both psychotic (hallucinatory-delusional) disorders and catatonic symptoms. A negative property is the development of obesity with prolonged use.

Risperidone (rispolept, speridan) is the most widely used antipsychotic from the group of atypical drugs. It has a general terminating effect on, as well as an elective effect on hallucinatory-delusional symptoms, catatonic symptoms,.

Rispolept-consta is a long-acting drug that provides long-term stabilization of the condition of patients and itself successfully relieves acute hallucinatory-paranoid syndromes of endogenous () genesis. Available in bottles of 25; 37.5 and 50 mg, administered parenterally, once every three to four weeks.

Risperidone, like olanzapine, causes a number of adverse complications in the endocrine and cardiovascular systems, which in some cases requires discontinuation of treatment. Risperidone, like all antipsychotics, the list of which is increasing every year, can cause neuroleptic complications up to NMS. Small doses of risperidone are used to treat persistent hypochondriacal syndrome.

Quetiapine (Seroquel), like others atypical antipsychotics, has a tropism for both dopamine and serotonin receptors. It is used to treat hallucinatory, paranoid syndromes, manic arousal. Registered as a drug with antidepressant and moderately pronounced stimulating activity.

Ziprasidone is a drug that acts on 5-HT-2 receptors, dopamine D-2 receptors, and also has the ability to block the reuptake of serotonin and norepinephrine. In this regard, it is used for the treatment of acute hallucinatory delusions and is contraindicated in the presence of pathology from the cardiovascular system, with arrhythmias.

Aripiprazole is used to treat all types of psychotic disorders, it has a positive effect on the recovery of cognitive functions during treatment.

Sertindole is comparable to haloperidol in terms of antipsychotic activity, it is also indicated for the treatment of sluggish-apathetic conditions, improving cognitive functions, and has antidepressant activity. Sertindole should be used with caution when indicating cardiovascular pathology, it can cause arrhythmias.

INVEGA (paliperidone extended release tablets) is used to prevent exacerbations of psychotic (hallucinatory-delusional, catatonic symptoms) in patients. The frequency of side effects is comparable to placebo.

Recently, clinical materials have been accumulating, indicating that atypical antipsychotics do not have a significant superiority over typical ones and are prescribed in cases where typical antipsychotics do not lead to a significant improvement in the condition of patients (B. D. Tsygankov, E. G. Agasaryan, 2006 , 2007).

Piperidine derivatives of the phenothiazine series

Thioridazine (melleril, sonapaks) was synthesized in order to obtain a drug that, having the properties of aminazine, would not cause pronounced somnolence and did not give extrapyramidal complications. Selective antipsychotic action is addressed to states of anxiety, fear,. The drug has some activating effect.

Neuleptil (propericiazine) detects a narrow spectrum of psychotropic activity aimed at stopping psychopathic manifestations with excitability, irritability.

Piperazine derivatives of phenothiazine

Triftazin (stelazin) is many times superior to chlorpromazine in terms of the strength of the antipsychotic effect, has the ability to stop,. Indicated for long-term maintenance treatment of delusional states, including flax structure. In small doses, it has a more pronounced activating effect than thioridazine. Effective in terms of treatment

Etaperazine is similar in action to triftazine, has a milder stimulating effect, and is indicated in the treatment of verbal, affective-delusional disorders.

Fluorphenazine (moditen, liogen) stops hallucinatory-, has a mild disinhibitory effect. The first drug that began to be used as a long-acting drug (moditen-depot).

Thioproperazine (mazheptil) has a very powerful antipsychotic terminating effect. Mazeptil is usually prescribed when treatment with other neuroleptics has no effect. In small doses, mazeptil helps well in treatment with complex rituals.

Butyrophenone derivatives

Haloperidol is the most powerful neuroleptic with a wide spectrum of action. Stops all types of excitation (catatonic, manic, delusional) faster than triftazin, and more effectively eliminates hallucinatory and pseudo-hallucinatory manifestations. It is indicated for the treatment of patients with the presence of mental automatisms. Used in treatment. In small doses, it is widely used to treat neurosis-like disorders (, hypochondriacal syndromes, senestopathy). The drug is used in the form of tablets, solution for intramuscular injection, in drops.

Haloperidol-decanoate - a drug of prolonged action for the treatment of delusional and hallucinatory-delusional states; indicated in cases of paranoid development. Haloperidol, like mazheptil, causes pronounced side effects with stiffness, tremor, and a high risk of developing neuroleptic malignant syndrome (NMS).

Trisedyl (trifluperidol) is similar in action to haloperidol, but its action is more powerful. Most effective in persistent verbal syndrome ( hallucinatory-paranoid). Contraindicated in organic lesions of the central nervous system.

Thioxanthene derivatives

Truxal (chlorprothixene) is a neuroleptic with a sedative effect, has an anti-anxiety effect, and is effective in the treatment of hypochondriacal and senestopathic disorders.

Fluanxol has a pronounced stimulating effect in small doses in the treatment of hypobulia and apathy. In large doses, it stops delusional disorders.

Klopiksol has a sedative effect, is indicated in the treatment of anxiety-delusional conditions.

Klopiksol-akufaz stops exacerbations, is used as a drug of prolonged action.

Side effects

Typical antipsychotics (triftazine, etaperazine, mazheptil, haloperidol, moditen)

The main side effects form the neuroleptic syndrome. The leading symptoms are extrapyramidal disorders with a predominance of either hypo- or hyperkinetic disorders. Hypokinetic disorders include drug-induced parkinsonism with increased muscle tone, rigidity, stiffness, and slowness of movement and speech. Hyperkinetic disorders include tremor, hyperkinesis (choreiform, athetoid, etc.). Most often, combinations of hypo- and hyperkinetic disorders are observed, expressed in various ratios. Dyskinesias are also observed quite often and can be hypo- and hyperkinetic in nature. They are localized in the mouth and are manifested by spasms of the muscles of the pharynx, tongue, larynx. In some cases, signs of akathisia are expressed with manifestations of restlessness, motor restlessness. A special group of side effects include tardive dyskinesia, which is expressed in involuntary movements of the lips, tongue, face, and sometimes in the choreiform movement of the limbs. Autonomic disorders are expressed in the form of hypotension, sweating, visual disturbances, dysuric disorders. There are also phenomena of agranulocytosis, leukopenia, disturbances of accommodation, urinary retention.

Antipsychotics (also known as antipsychotics or strong tranquilizers) are a class of psychiatric drugs used primarily to control psychosis (including delusions, hallucinations, and thought disorders), in particular for and , and are increasingly being used to control non-psychotic disorders (ATC code N05A). The word "neuroleptic" comes from the Greek words "νεῦρον" (neuron, nerve) and "λῆψις" ("capture"). The first generation of antipsychotics, known as typical antipsychotics, were discovered in the 1950s. Most of the second generation drugs known as atypical antipsychotics were developed more recently, although the first atypical antipsychotic, clozapine, was discovered in the 1950s and introduced into clinical practice in the 1970s. Both generations of antipsychotics tend to block receptors in the brain's dopamine pathways, but atypical antipsychotics also generally act on serotonin receptors. Antipsychotics are more effective than placebo in treating the symptoms of psychosis, but some patients do not fully or even partially respond to treatment. The use of antipsychotics is associated with significant side effects, primarily movement disorders and weight gain.

medical application

Antipsychotics are most commonly used for the following indications:

Antipsychotics are used to treat dementia or insomnia only if other treatments have failed. They are used to treat children only if other treatments have failed or if the child is suffering from psychosis.

Schizophrenia

Antipsychotics are a key component of schizophrenia treatment recommended by the National Institute for Health and Clinical Excellence (NICE), the American Psychiatric Association, and the British Society for Psychopharmacology. The main effect of antipsychotic treatment is to reduce the so-called "positive" symptoms of the disease, including delusions and hallucinations. There is mixed evidence to support a significant effect of antipsychotics on the negative symptoms (eg, apathy, lack of emotional affect, and lack of interest in social interactions) or cognitive symptoms (disordered thinking, reduced ability to plan and complete tasks) of schizophrenia. In general, the effectiveness of antipsychotics in reducing positive and negative symptoms appears to increase with increasing severity of baseline symptoms. The use of antipsychotics in the treatment of schizophrenia includes prophylaxis in patients with symptoms suggestive of an increased risk of developing psychosis, treatment of the first episode of psychosis, supportive care, and treatment of recurrent episodes of acute psychosis.

Prevention of psychosis and improvement of symptoms

Lines of tests such as PACE (Personal and Crisis Assessment) and COPS (Prodromal Syndrome Criteria), which measure low-level psychotic symptoms, and other tests focusing on cognitive impairment (basic symptoms) are used to assess patients with early symptoms of psychosis. Combined with family history information, these tests can identify "high-risk" patients who have a 20-40% risk of disease progression to full-blown psychosis within 2 years. These patients are often prescribed low doses of antipsychotics to reduce symptoms and prevent the disease from progressing to full-blown psychosis. Despite the generally positive effect of antipsychotics in reducing symptoms, clinical trials conducted to date provide little evidence that early use of antipsychotics, alone or in combination with cognitive behavioral therapy, provides improved long-term outcomes in patients with prodromal symptoms. .

First episode of psychosis

NICE recommends that all individuals presenting with a first episode of full-blown psychosis be treated with antipsychotic medication and cognitive behavioral therapy (CBT). NICE recommends warning CBT-only patients that combination therapy is more effective. The diagnosis of schizophrenia is usually not made at the first episode of psychosis because up to 25% of patients who seek help after the first episode of psychosis are eventually diagnosed with bipolar disorder. Treatment goals for these patients include symptom reduction and potential improvement in long-term outcomes. Randomized clinical trials have shown the effectiveness of antipsychotics in achieving the first goal, while first and second generation antipsychotics show equal effectiveness. Evidence that early treatment has a beneficial effect on long-term outcomes is controversial.

Recurrent psychotic episodes

Placebo-controlled trials of first- and second-generation antipsychotics consistently demonstrate superiority of the active drug over placebo in the suppression of psychotic symptoms. A large meta-analysis of 38 studies of antipsychotics in acute psychotic episodes of schizophrenia reported an effect size of about 0.5. There is almost no difference in efficacy among approved antipsychotics, including both first- and second-generation drugs. The effectiveness of such drugs is suboptimal. In several patients, complete resolution of symptoms has been achieved. The response rate, calculated using various indicators of symptom reduction, was low. Data interpretation is complicated by high placebo response rates and selective publication of clinical trial results.

Supportive care

Most patients treated with antipsychotics show a response within 4 weeks. The goals of continued treatment are to maintain symptom suppression, prevent relapse, improve quality of life, and engage in psychosocial therapy. Maintenance therapy with antipsychotics is clearly superior to placebo in preventing relapse, but is associated with side effects such as weight gain, movement disorders, and a high dropout rate. A 3-year trial of people receiving maintenance therapy after an acute psychotic episode found that 33% had a sustained improvement in symptoms, 13% achieved remission, and only 27% reported a satisfactory quality of life. The effect of relapse prevention on long-term outcomes is uncertain, and historical studies show little difference in long-term outcomes before and after administration of antipsychotics. An important challenge in the use of antipsychotics for relapse prevention is the low compliance rate. Despite the relatively high rate of side effects associated with these drugs, some evidence, including the high dropout rate of participants in the placebo group compared to the treatment groups in randomized clinical trials, suggests that most patients who stop treatment do so because suboptimal performance.

Bipolar disorder

Antipsychotics are often used in combination with mood stabilizers such as /valproate as first-line therapy for the treatment of manic and mixed episodes associated with bipolar disorder. The reason for using this combination is the therapeutic delay in the action of the aforementioned mood stabilizers (the therapeutic effects of valproate are usually observed after five days after the start of treatment, and lithium - at least a week) and the relatively rapid anti-manic effects of antipsychotic drugs. Antipsychotics have shown efficacy when used alone in acute manic/mixed episodes. Three atypical antipsychotics (lurasidone, olanzapine, and quetiapine) have also been found to be effective in the treatment of bipolar depression when used alone. Only olanzapine and quetiapine have been shown to be effective for a wide range of preventive effects (i.e., for all three types of episodes - manic, mixed and depressive) in patients with bipolar disorder. A recent Cochrane review also found that olanzapine has a less favorable risk/benefit ratio than lithium as maintenance therapy for bipolar disorder. The American Psychiatric Association and the UK National Institute for Health and Care Excellence recommend antipsychotics for the management of acute psychotic episodes in schizophrenia or bipolar disorder, and as long-term maintenance treatment to reduce the likelihood of further episodes. They argue that the response to any neuroleptic may be different, so trials should be conducted in this direction, and that lower doses should be preferred when possible. A number of studies have observed levels of adherence to antipsychotic drug regimens and found that discontinuation in patients is associated with higher rates of relapse, including hospitalization.

Dementia

Testing for symptoms of dementia is required as an assessment of the underlying cause of the illness before antipsychotics are prescribed. When used in the treatment of dementia in the elderly, antipsychotics have shown modest efficacy compared with placebo in controlling aggression or psychosis and a fairly large number of serious side effects. Thus, antipsychotics are not recommended for routine use in the treatment of aggressive dementia or psychosis, but they may be considered as an option in some cases where there is severe stress or risk of physical harm to others. Psychosocial therapies may reduce the need for antipsychotic medications.

Unipolar depression

A number of atypical antipsychotics have some advantages when used in addition to other treatments for clinical depression. Aripiprazole, and olanzapine (when used in combination with ) have been approved by the US Food and Drug Administration (FDA) for this indication. Their use, however, is associated with an increased risk of side effects.

Other indications

In addition to the above indications, antipsychotics may be used to treat anxiety, personality disorders, and anxiety in patients with dementia. Evidence, however, does not support the use of atypical antipsychotics for eating disorders or personality disorders. Risperidone may be useful in the treatment of obsessive-compulsive disorder. The use of low-dose antipsychotics for insomnia, although common, is not recommended because there is little evidence of benefit and the risk of side effects. Low-dose antipsychotics may also be used to treat the impulsive behavioral and cognitive-perceptual symptoms of borderline personality disorder. In children, neuroleptics may be used in cases of social behavior disorders, mood disorders, and general developmental disorders or mental retardation. Antipsychotics are rarely recommended for the treatment of Tourette's syndrome because, despite their effectiveness, these drugs have a lot of side effects. The situation is similar for autism spectrum disorders. Much of the evidence regarding off-label use of antipsychotics (eg, for dementia, OCD, post-traumatic stress disorder, personality disorder, Tourette's syndrome) lacks scientific evidence to support such use, especially when there is strong evidence of an increased risk of stroke , convulsions, significant weight gain, sedation and gastrointestinal problems. A British review of the unlicensed use of antipsychotics in children and adolescents found similar findings and concerns. A survey of children with developmental disorders found that 16.5% of patients took antipsychotic drugs, most often for irritability, aggression and excitement. Risperidone has been approved by the US FDA for the treatment of irritability in autistic children and adolescents. Aggressive defiant behavior in adults with intellectual disabilities is often also treated with antipsychotics, despite the lack of evidence for such use. A recent randomized controlled trial, however, found no benefit of this treatment compared to placebo. The study did not recommend the use of antipsychotics as an acceptable permanent treatment.

Typical and atypical antipsychotics

It is not clear whether atypical antipsychotics (second generation) have an advantage over first generation antipsychotics. Amisulpride, olanzapine, risperidone, and clozapine may be more effective, but they also have more severe side effects. Typical and atypical antipsychotics have equal dropout rates and relapse rates when used at low to moderate doses. Clozapine is an effective treatment for patients who respond poorly to other drugs ("treatment-resistant" schizophrenia), but clozapine has the potentially serious side effect of agranulocytosis (decreased white blood cell count) in less than 4% of people. Due to research bias, the accuracy of comparing atypical antipsychotics is a problem. In 2005, the US government agency, the National Institute of Mental Health, published the results of a major independent study (Project CATIE). None of the atypical antipsychotics studied (risperidone, quetiapine, and ziprasidone) showed superiority over the typical antipsychotic perphenazine in the testing methods used, and these drugs caused no fewer side effects than the typical antipsychotic perphenazine, although more patients discontinued perphenazine due to extrapyramidal effects. compared with atypical antipsychotics (8% versus 2-4%). In terms of patient compliance with study medication instructions, no significant differences were found between the two types of neuroleptics. Many researchers question the usefulness of prescribing atypical antipsychotics as first-line drugs, and some even question the distinction between the two classes of antipsychotics. Other researchers point to a significantly higher risk of developing tardive dyskinesia and extrapyramidal symptoms with typical antipsychotics and for this reason alone recommend atypical drugs as first-line treatment, despite a greater risk of metabolic side effects. The UK government agency NICE recently revised its recommendations in favor of atypical antipsychotics, stating that the choice should be individual based on the specific drug profile and patient preferences.

Side effects

You should not take more than one antipsychotic drug at the same time, except in unusual circumstances due to an increase in the number and severity of side effects of the drugs. Common (≥ 1% and up to 50% of cases for most antipsychotics) side effects of antipsychotics include:

Lethargy (especially common with clozapine, olanzapine, quetiapine, chlorpromazine, and zotepine)

Headache

Dizziness

• Anxiety

  Extrapyramidal side effects (especially common with first-generation antipsychotics), including:

Akathisia is a feeling of inner restlessness.

Dystonia

parkinsonism

Hyperprolactinemia (rare with clozapine, quetiapine, and aripiprazole), which can lead to:

Galactorrhea - unusual secretion of breast milk.

Gynecomastia

Sexual dysfunction (in both sexes)

Osteoporosis

orthostatic hypotension

Weight gain (especially with clozapine, olanzapine, quetiapine, and zotepine)

Anticholinergic side effects (when taking olanzapine, clozapine, and less likely risperidone) such as:

blurred vision

Dry mouth (although salivation may also occur)

Decreased sweating

Tardive dyskinesia is more common in patients taking first-generation highly active antipsychotics such as haloperidol, and occurs mainly after chronic, rather than short-term, treatment. It is characterized by slow, repetitive, uncontrolled, and aimless movements, most commonly of the face, lips, legs, or torso, which are usually resistant to treatment and often irreversible. The frequency of PD is about 5% per year with the use of antipsychotic drugs (regardless of the drug used).

Rare/Uncommon (<1% случаев для большинства антипсихотических препаратов) побочные эффекты антипсихотических препаратов включают:

Weight gain as a result of histamine H1 and serotonin 5-HT2C receptor antagonism and possibly through interactions with other neurochemical pathways in the central nervous system

Neuroleptic Malignant Syndrome is a potentially life-threatening condition characterized by:

Autonomic instability, which can be manifested by tachycardia, nausea, vomiting, sweating, etc.

Hyperthermia - an increase in body temperature.

Change in mental status (confusion, hallucinations, coma, etc.)

Muscle stiffness

Laboratory abnormalities (eg, elevated creatinine kinase, decreased plasma iron, electrolyte disturbances, etc.)

pancreatitis

Increased QT interval, most notable in patients taking amisulpride, pimozide, sertindole, thioridazine, and ziprasidone

Convulsions, which are especially common in patients taking chlorpromazine and clozapine.

Thromboembolism

myocardial infarction

• Ventricular tachycardia type "pirouette"

Some studies have shown a reduction in life expectancy associated with the use of antipsychotic drugs. Antipsychotics may also increase the risk of early death in people with dementia. Antipsychotics tend to worsen symptoms in people with depersonalization disorder. Antipsychotic polypharmacy (taking two or more antipsychotics at the same time) is common practice, but is not evidence-based or recommended, and there are initiatives to limit such use. In addition, the use of excessively high doses (often as a result of polypharmacy) continues despite clinical guidelines and evidence that such use is usually not more effective, but is usually associated with more harm to the patient.

Other

In schizophrenia, over time, there is a loss of gray matter in the brain and other structural changes. A meta-analysis of the effects of antipsychotic treatment on gray matter loss and structural changes shows conflicting findings. A 2012 meta-analysis found that patients treated with first-generation antipsychotics experienced greater gray matter loss compared to those treated with second-generation atypical antipsychotics. A protective effect of atypical neuroleptics has been proposed as one possible explanation. A second meta-analysis suggested that treatment with antipsychotics may be associated with increased gray matter loss. Latent, long-term forms of akathisia are often overlooked or mistaken for post-psychotic depression, particularly in the absence of the extrapyramidal aspect that psychiatrists expect when looking for signs of akathisia.

Discontinuation

Withdrawal symptoms from antipsychotics may occur when dosage is reduced and when use is discontinued. Withdrawal symptoms may include nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, myalgia, paresthesia, restlessness, agitation, and insomnia. The psychological symptoms of the syndrome may include psychosis, and may be mistaken for a relapse of the underlying illness. Improving withdrawal control may improve people's chances of successfully discontinuing antipsychotics. During withdrawal from an antipsychotic, symptoms of tardive dyskinesia may decrease or persist. Withdrawal symptoms may occur when a patient switches from one antipsychotic to another (presumably due to differences in drug efficacy and receptor activity). Such symptoms may include cholinergic effects and movement syndromes, including dyskinesias. These side effects are more likely to occur when switching antipsychotics rapidly, so a gradual switch from one antipsychotic to another minimizes these withdrawal effects. The British National Formulary recommends phasing out when antipsychotic treatment is stopped to avoid acute withdrawal symptoms or rapid relapse. The process of cross-titration involves gradually increasing the dose of the new drug while gradually decreasing the dose of the old drug.

Mechanism of action

All antipsychotic drugs tend to block D2 receptors in the dopamine pathway in the brain. This means that dopamine released in these pathways will have less of an effect. Excess dopamine release in the mesolimbic pathway has been associated with psychotic experiences. It has also been shown that a decrease in dopamine release in the prefrontal cortex, as well as an excess of dopamine in all other pathways, have also been associated with psychotic experiences caused by abnormal functioning of the dopaminergic system in patients suffering from schizophrenia or bipolar disorder. Various neuroleptics, such as haloperidol and chlorpromazine, suppress dopamine in its pathways, ensuring the normal functioning of dopamine receptors. In addition to their dopamine antagonistic effects, antipsychotics (particularly atypical antipsychotics) also antagonize 5-HT2A receptors. Various alleles of the 5-HT2A receptor have been associated with the development of schizophrenia and other psychoses, including depression. There is evidence of higher concentrations of 5-HT2A receptors in cortical and subcortical areas, in particular, in the right caudate nucleus. The agonists of these same receptors are psychedelics, which explains the relationship between psychedelic drugs and schizophrenia. Typical antipsychotics are not particularly selective, they also block dopamine receptors in the mesocortical pathway, the tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the undesirable side effects of typical antipsychotics. They are usually classified on a spectrum from low to high potency, with potency referring to the drug's ability to bind to dopamine receptors rather than the potency of the drug. Active doses of highly potent neuroleptics such as haloperidol are as low as a few milligrams and cause less drowsiness and sedation than low-potency antipsychotics such as chlorpromazine and thioridazine, which have active doses of hundreds of milligrams. The latter has more pronounced anticholinergic and antihistamine activity, which may counteract the side effects associated with dopamine. Atypical antipsychotics have a similar blocking effect on D2 receptors, however, most of them also act on serotonin receptors, especially 5-HT2A and 5-HT2C receptors. Both clozapine and quetiapine have binding long enough to cause antipsychotic effects, but not long enough to cause extrapyramidal side effects and prolactin hypersecretion. 5-HT2A antagonism increases dopaminergic activity in the nigrostriatal pathway, resulting in a reduction in extrapyramidal side effects among atypical antipsychotics.

Story

The original antipsychotics were largely discovered by accident and then tested to see if they worked. The first neuroleptic, chlorpromazine, was developed as a surgical anesthetic. It was first used in psychiatry for its powerful sedative effect; at the time, the drug was considered a temporary "pharmacological lobotomy." Lobotomy was used at the time to treat many behavioral disorders, including psychosis, although its side effect was a marked reduction in behavioral and mental functioning of all kinds. However, chlorpromazine has been shown to reduce the effects of psychosis more effectively than lobotomy, even though it has strong sedative effects. The neurochemistry underlying its action has since been studied in detail, after which subsequent antipsychotic drugs have been discovered. The discovery of the psychoactive effects of chlorpromazine in 1952 led to a significant decrease in the use of methods such as mechanical restraint of the mentally ill, seclusion and sedation to control patients, and also led to further research, due to which tranquilizers and most other drugs were discovered. time to control mental illness. In 1952, Henri Labori described chlorpromazine as a drug that only causes the patient (non-psychotic, non-manic) to be indifferent to what is happening around. Jean Delay and Pierre Deniker described it as a means to control mania or psychotic arousal. Delay claimed to have discovered a cure for anxiety applicable to all people, while Deniker's team claimed to have discovered a cure for psychotic illness. Until the 1970s, there was some debate in psychiatry over the most appropriate term to describe new drugs. In the late 1950s, the most widely used term was "antipsychotics" and then "major tranquilizers", after which - "tranquilizers". The first recorded use of the term "tranquilizer" dates back to the early nineteenth century. In 1953, Frederick F. Jonkman, a chemist at the Swiss company Cibapharmaceutical, first used the term "tranquilizer" to differentiate reserpine from older generation sedatives. the word "neuroleptic" comes from the Greek: "νεῦρον" (neuron, originally meaning "veins", but today it means nerves) and "λαμβάνω" (lambanō, meaning "to possess"). Thus, the word means "to take control of the nerves." This may refer to the common side effects of neuroleptics, such as reduced activity in general, as well as lethargy and impaired movement control. Although these effects are unpleasant, and in some cases harmful, they, along with akathisia, were once considered a reliable sign that the drug was working. The term "ataraxia" was coined by the neurologist Howard Fabing and the classicist Alistair Cameron to describe the observed effect of mental indifference and withdrawal in patients treated with chlorpromazine. The term comes from the Greek adjective "ἀτάρακτος" (ataraktos), which means "undisturbed, unexcited, without confusion, steady, calm". In using the terms "tranquilizer" and "ataractic", physicians distinguished between "major tranquilizers" or "large ataractics", drugs used to treat psychosis, and "minor tranquilizers" or "minor ataractics" used to treat neuroses. While popular in the 1950s, these terms are rarely used today. They have now been abandoned in favor of the term "neuroleptics" (antipsychotics), which refers to the desired effects of the drug. Today, the term "minor tranquilizer" may refer to anxiolytics and/or hypnotics, such as and , which have some antipsychotic properties and are recommended for concurrent use with antipsychotic drugs and are useful for insomnia or narcotic psychosis. They are powerful sedatives (and have the potential to be addictive). Antipsychotics can be divided into two groups: typical antipsychotics (first generation drugs) and atypical antipsychotics (second generation antipsychotics). Typical antipsychotics are classified according to their chemical structure, while atypical antipsychotics are classified according to their pharmacological properties. They include serotonin-dopamine antagonists, multi-receptor antipsychotics (MARTA), and dopamine partial agonists, which are often categorized as atypical antipsychotics.

Society and culture

Sales

Antipsychotics were once among the most sold and profitable drugs. For example, in 2008, worldwide sales of antipsychotics were $22 billion. By 2003, an estimated 3.21 million patients were receiving antipsychotics in the United States, for a total of $2820,000,000. More than 2/3 of prescriptions were filled for new , the more expensive, atypical antipsychotics, each averaging $164 a year in sales, compared to $40 for older generation antipsychotics. By 2008, US sales reached $14.6 billion, making antipsychotics the top-selling drug class in the US.

Lineups

Antipsychotics are sometimes used as part of mandatory psychiatric treatment in an inpatient (hospital) or outpatient clinic. They can be given orally or, in some cases, as a long-acting (depot) injection into the gluteus or deltoid muscle.

controversy

Special patient groups

Individuals with dementia who exhibit behavioral and psychological symptoms should not take antipsychotics until other treatments have been tried. Antipsychotics increase the risk of cerebrovascular effects, parkinsonism or extrapyramidal symptoms, sedation, confusion and other cognitive adverse effects, weight gain, and increased mortality in this group of patients. Physicians and caregivers of people with dementia should try to treat symptoms, including agitation, aggression, apathy, anxiety, depression, irritability, and psychosis, using alternative therapies.

List of antipsychotics

List of used literature:

Finkel R, Clark MA, Cubeddu LX (2009). Pharmacology (4th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 151. ISBN 9780781771559.

Goikolea JM, Colom F, Torres I, Capapey J, Valentí M, Undurraga J, Grande I, Sanchez-Moreno J, Vieta E (2013). "Lower rate of depressive switch following antimanic treatment with second-generation antipsychotics versus haloperidol". J Affect Disord 144(3): 191–8. doi:10.1016/j.jad.2012.07.038. PMID 23089129.

"American Psychiatric Association Five Things Physicians and Patients Should Question". Choosing Wisely. Retrieved on September 23, 2013.

Toshi A. Furukawa, Stephen Z. Levine, Shiro Tanaka, Yair Goldberg, Myrto Samara, John M. Davis, Andrea Cipriani & Stefan Leucht (November 2014). "Initial Severity of Schizophrenia and Efficacy of Antipsychotics: Participant-Level Meta-analysis of 6 Placebo-Controlled Studies". JAMA psychiatry 72: 14. doi:10.1001/jamapsychiatry.2014.2127. PMID 25372935.

Leucht S, Arbter D, Engel RR, Kissling W, Davis JM (April 2009). How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Mol. Psychiatry 14(4): 429–47. doi:10.1038/sj.mp.4002136. PMID 18180760.

Biopsychosocial model of schizophrenia

The approach to the treatment of mental disorders is determined by the level of knowledge about their origin and development mechanisms. This lecture presents the role of various components of therapy in overcoming mental illness.
Currently, the biopsychosocial model is recognized by most professionals around the world as the most productive approach to considering such a mental illness as schizophrenia. "Bio" means that in the development of this disease an important role is played by the biological characteristics of the body - the functioning of brain systems, metabolism in it. These biological features predetermine the next component - some features of the psyche both in the process of its development in childhood and functioning in adulthood.

It has been shown that patients with schizophrenia have features in the functioning of brain nerve cells, the transmitter of information between which is the neurotransmitter dopamine (“neuro” means a nerve cell, “mediator” means a transmitter, mediator).

The system of neurons, the exchange of information between which occurs due to the dopamine molecule, is called the dopamine neurotransmitter system. Dopamine at the right time is released from the nerve ending of one cell and, once in the space between two cells, finds special sites (the so-called dopamine receptors) on the process of another - a neighboring cell, to which it joins. Thus, information is transferred from one brain cell to another.

There are several subsystems in the dopamine system of the brain. One is responsible for the work of the cerebral cortex, the other, extrapyramidal, for muscle tone, the third for the production of hormones in the pituitary gland.

"Psycho" indicates the psychological characteristics of a person, making him more vulnerable to the effects of various stressors (circumstances that cause a state of stress in a person, that is, a physiological and psychological reaction of adaptation, or a reaction to maintain balance). Such greater vulnerability than others means that even those circumstances that other people overcome painlessly can cause a painful reaction in these highly vulnerable people. Such a reaction can be the development of psychosis. They talk about the individually reduced stress resistance of these people, i.e. decreased ability to respond to stress without developing a disease state.

From practice, examples are well known when such events as the transition from class to class, from school to school, infatuation with a classmate or classmate, graduation from school or institute, i.e. events that are frequent in the lives of most people became "starters" in the development of schizophrenia in people predisposed to this disease. We are talking here about the role in the development of the disease of social factors that a person encounters when interacting with other people. An indication of the role of social circumstances that become stressful for vulnerable people is contained in the component of the term "biopsychosocial" model.

From what has been said, it becomes obvious that help for people suffering from schizophrenia should consist of attempts to influence all three components involved in the development of the disease and, which is very important, supporting this disease.

In modern psychiatry, help for people suffering from schizophrenia consists of: 1) drug treatment(with the help of drugs), which is aimed at normalizing the functioning of the dopamine system of nerve cells in the brain and, as a result, at increasing stress resistance; 2) psychological treatment, i.e. psychotherapy aimed at correcting those psychological characteristics that contributed to the development of the disease, psychotherapy aimed at developing the ability to cope with the symptoms of the disease, as well as psychotherapy, the purpose of which is to create an obstacle to the psychological consequences of the disease, for example, detachment from other people; 3) social measures aimed at maintaining the functioning of a person in society - support in maintaining the patient's professional status, social activity, training his social interaction skills, taking into account social requirements and norms, as well as measures that would help normalize interaction with loved ones. The last component involves not only helping the patient himself, but also working with the social environment, in particular with family members, who, last but not least, need help and support.

Antipsychotics: main and side effects

The main group of pharmacological psychotropic drugs that are effective in helping people with schizophrenia is the group neuroleptics.

psychotropic called drugs that affect the activity of the brain and normalize mental functions (perception, thinking, memory, etc.). There are several groups of psychotropic drugs that mainly affect the violation of one or another mental function: antipsychotics (drugs that can suppress delusions, hallucinations and other productive symptoms), antidepressants (increasing depressed mood), tranquilizers (reducing anxiety), mood stabilizers (mood stabilizers) , antiepileptic, or anticonvulsant, drugs, nootropics and metabolic drugs (improving metabolism in the nerve cells themselves).

The main pharmacological action of antipsychotics is the blocking of dopamine receptors, resulting in the normalization of the activity of the dopamine system of brain cells, namely, the decrease in this activity to an optimal level. Clinically, i.e. at the level of symptoms of the disease, this corresponds to a noticeable decrease or complete disappearance of the productive symptoms of the disease (delusions, hallucinations, catatonic symptoms, agitation, attacks of aggression). The ability of neuroleptics to completely or partially suppress such manifestations of psychosis as delusions, hallucinations, catatonic symptoms is called antipsychotic action.

In addition to antipsychotics, neuroleptics have a number of other effects:

sedative (sedative), which allows the use of antipsychotics to reduce internal tension, bouts of excitement and even aggression;

sleeping pills, and an important advantage of neuroleptics as hypnotics is that, unlike tranquilizers, they do not cause complications such as the formation of mental and physical dependence, and after normalization of sleep can be canceled without any consequences;

· activating, i.e. the ability of some antipsychotics to reduce passivity;

Normothymic (stabilizing mood background), especially characteristic of the so-called atypical antipsychotics (see below), which, due to the presence of this effect, can be used to prevent the next attack of schizophrenia or schizoaffective psychosis or reduce its severity;

· "corrective behavior" effect - the ability of some neuroleptics to smooth out behavioral disorders (for example, painful conflict, the desire to run away from home, etc.) and normalize cravings (food, sexual);

antidepressant, i.e. the ability to improve mood;

anti-manic - the ability to normalize a pathologically elevated, elated mood;

improvement of cognitive (cognitive) mental functions - the ability to normalize the process of thinking, increase its consistency and productivity;

· vegetative stabilizing (stabilization of vegetative functions - sweating, heart rate, blood pressure, etc.).

These effects are associated with the influence of neuroleptics not only on dopamine, but also on other systems of nerve cells in the brain, in particular on the noradrenal and serotonin systems, in which the transmitter of information between cells is, respectively, norepinephrine or serotonin.

Table 1 presents the main effects of antipsychotics and lists drugs that have these properties.

Side effects are also associated with the effect of antipsychotics on the dopamine system of brain nerve cells, i.e. unwanted effects. This is an opportunity, simultaneously with the provision of an antipsychotic effect, to influence muscle tone or change some parameters of hormonal regulation (for example, the menstrual cycle).

When prescribing antipsychotics, their effect on muscle tone is always taken into account. These effects are unwanted (side effects). Since muscle tone is regulated by the extrapyramidal system of the brain, they are called extrapyramidal side effects. Unfortunately, most often the effect of antipsychotics on muscle tone cannot be avoided, but this effect can be corrected with the help of cyclodol (parkopan), akineton and a number of other drugs (for example, tranquilizers), which in this case are called correctors. To successfully select therapy, it is important to be able to recognize these side effects.

Table 1
The main effects of neuroleptics

	Classical or typical antipsychotics	Atypical antipsychotics and new generation drugs
Antipsychotic	Haloperidol Mazeptil Trifluoperazine (triftazin, stelazin) Etaperazine moditen depot Chlorprothixene Clopixol Fluanxol	Azaleptin (leponex) Zyprexa Rispolept (speridan, risset) Seroquel Abilify
Sedative	Aminazin Tizercin Haloperidol Clopixol Etaperazine Trifluoperazine (triftazine, stelazine)	Azaleptin Zyprexa Seroquel
Hypnotic	Tizercin Aminazin Chlorprothixene Thioridazine (sonapax)	Azaleptin Seroquel
activating	Frenolon Mazeptil Fluanxol	Rispolept (speridan, risset)
Normothymic	Clopixol Fluanxol	Azaleptin Rispolept Seroquel
"Correct Behavior"	Thioridazine (sonapax) Neuleptyl Piportil	Azaleptin Seroquel
antidepressant	Trifluoperazine (triftazin, stelazin) Chlorprothixene Fluanxol	Rispolept (speridan, risset) Seroquel
anti-manic	Haloperidol Tizercin Thioridazine (sonapax) Clopixol	Azaleptin Zyprexa Rispolept (speridan, risset) Seroquel
Cognitive Improvement	Etaperazine	Azaleptin Zyprexa Seroquel Rispolept (speridan, risset)
Vegetostabilizing	Etaperazine Frenolon Sonapax

The effect of neuroleptics on muscle tone can manifest itself in different ways at the stages of therapy. So, in the first days or weeks of taking antipsychotics, the development of so-called muscular dystonia is possible. This is a spasm in one or another muscle group, most often in the muscles of the mouth, oculomotor muscles, or neck muscles. Spasmodic muscle contraction can be unpleasant, but is easily eliminated by any corrector.

With a longer intake of neuroleptics, the development of phenomena is possible drug parkinsonism: trembling in the limbs (tremor), muscle stiffness, including stiffness of the muscles of the face, stiff gait. When the initial manifestations of this side effect occur, the feeling in the legs (“cotton legs”) may change. Opposite sensations may also appear: feelings of anxiety with a constant desire to change the position of the body, the need to move, walk, move the legs. Subjectively, the initial manifestations of this side effect are experienced as discomfort in the legs, a desire to stretch, a feeling of "restless legs". This type of extrapyramidal side effect is called akathisia, or restlessness.

With many months, and more often many years of taking antipsychotics, it is possible to develop tardive dyskinesia, which is manifested by involuntary movements in one or another muscle group (usually the muscles of the mouth). The origin and mechanism of this side effect is being actively studied. There is evidence that its development is facilitated by abrupt changes in the scheme of taking antipsychotics - sudden interruptions, drug withdrawal, which is accompanied by sharp fluctuations in the concentration of the drug in the blood. Table 2 shows the main manifestations of extrapyramidal side effects and tardive dyskinesia and measures for their elimination.

The start of taking correctors to reduce the severity of extrapyramidal side effects may coincide with the moment of prescribing an antipsychotic, but may also be delayed until such effects appear. The corrector dose required to prevent the development of extrapyramidal side effects is individual and is selected empirically. Usually it is from 2 to 6 tablets of cyclodol or akineton per day, but not more than 9 tablets per day. A further increase in their dose does not enhance the corrective effect, but is associated with the likelihood of side effects of the corrector itself (for example, dry mouth, constipation). Practice shows that not all people have extrapyramidal side effects of antipsychotics and that not in all cases their correction is required during the course of treatment with antipsychotics. In about two-thirds of patients taking antipsychotics for more than 4-6 months, the corrector dose can be reduced (and in some cases even canceled), and no extrapyramidal side effects are observed. This is due to the fact that with a sufficiently long intake of neuroleptics in the brain, compensatory mechanisms for maintaining muscle tone are activated and the need for correctors decreases or disappears.

table 2
The main neurological side effects of antipsychotic therapy and ways to correct them

Side effect	Main manifestations
Muscular dystonia (first days, weeks)	Spasm in the muscles of the mouth, eyes, neck	Cyclodol or akineton 1-2 tab. under the tongue Any tranquilizer (phenazepam, nozepam, elenium, etc.) 1 tab. under the tongue Phenobarbital (or 40-60 drops of Corvalol or Valocordin) Caffeine (strong tea or coffee) Ascorbic acid up to 1.0 g orally in solution Piracetam 2-3 capsules orally
Drug parkinsonism (first weeks, months)	Tremor, muscle stiffness, skin greasiness	Cyclodol (Parkopan) or Akineton: 3-6 tab. per day, but not more than 9 tab. up to 3 tab. in a day
Akathisia (first weeks, months)	Restlessness, restlessness, desire to move, feeling of "restless legs"	up to 30 mg per day Tranquilizer (phenazepam, etc.) up to 3 tab. in a day
Tardive dyskinesia (months and years from the start of taking the drugs)	Involuntary movements in individual muscle groups	Propranolol (anaprilin, obzidan) - in the absence of contraindications up to 30 mg per day Tremblex

Characteristics of new generation antipsychotics: new opportunities and limitations

Revolutionary in the field of treatment of schizophrenia and other mental disorders was the creation of a new class - the so-called atypical antipsychotics. The first such drug was clozapine (leponex, azaleptin).

It is noted that when prescribing it, characteristic extrapyramidal effects do not develop or are observed only in the most sensitive patients to the drug or when prescribing medium and high doses of the drug. In addition, unusual components of the effect of this drug were noted - normothymic (i.e., the ability to stabilize the background of mood), as well as an improvement in cognitive functions (restoration of concentration, thinking sequence). Subsequently, new antipsychotics were introduced into psychiatric practice, which received the stable name of atypical, such as risperidone (rispolept, speridan, risset), olanzanpine (ziprexa), quetiapine (seroquel), amisulpride (solian), ziprasidone (zeldox), abilify. Indeed, during therapy with the listed drugs, extrapyramidal side effects develop much less frequently compared with treatment with classical antipsychotics and only when prescribing high or medium doses. This feature determines their significant advantage over classical ("typical" or "conventional") antipsychotics.

In the process of studying the effectiveness of atypical antipsychotics, other distinctive features were also identified. In particular, the effectiveness of clozapine (leponex, azaleptin) in the treatment of resistant, i.e. resistant to the action of classical antipsychotics, conditions. An important property of atypical antipsychotics is their the ability to stabilize the emotional sphere, reducing mood swings in the direction of both a decrease (in depression) and a pathological increase (in a manic state). Such an effect is called normothymic. Its presence allows the use of atypical neuroleptics, such as clozapine (azaleptin), rispolept and seroquel, as drugs that prevent the development of another acute attack of schizophrenia or schizoaffective psychosis. Recently, the ability of new generation neuroleptics to exert positive effect on cognitive (cognitive) functions in people with schizophrenia. These drugs help restore the sequence of thinking, improve concentration, resulting in an increase in intellectual productivity. Such characteristics of new generation antipsychotics as the ability to normalize the emotional sphere, activate patients, and have a positive effect on cognitive functions explain the widespread opinion about their effect not only on the productive (delusions, hallucinations, catatonic symptoms, etc.), but also on the so-called negative ( decreased emotional response, activity, impaired thinking) symptoms of the disease.

While recognizing the noted benefits of atypical neuroleptics, it should be noted that they, like any other drugs, cause side effects. In cases where they have to be prescribed in high doses, and sometimes even in medium doses, extrapyramidal side effects still appear and the advantage of atypical antipsychotics over classical ones in this regard decreases. In addition, these drugs may have a range of other side effects similar to those of classic antipsychotics. In particular, the appointment of rispolept can lead to a significant increase in the level of prolactin (the pituitary hormone that regulates the function of the gonads), which is associated with the appearance of symptoms such as amenorrhea (cessation of menstruation) and lactorrhoea in women and breast engorgement in men. This side effect was noted during therapy with risperidone (Rispolept), olanzapine (Zyprexa), ziprasidone (Zeldox). In some cases, when prescribing such atypical neuroleptics as olanzapine (Zyprexa), clozapine (Azaleptin), risperidone (Rispolept), an individual side effect is possible in the form of an increase in body weight, sometimes significant. The latter circumstance limits the use of the drug, since excess body weight of a certain critical value is associated with the risk of developing diabetes mellitus.

The appointment of clozapine (azaleptin) involves regular monitoring of the blood picture with the study of the number of leukocytes and platelets, since in 1% of cases it causes inhibition of the blood germ (agranulocytosis). It is necessary to conduct a blood test once a week in the first 3 months of taking the drug and once a month thereafter throughout the course of treatment. When using atypical antipsychotics, side effects such as swelling of the nasal mucosa, nosebleeds, lowering blood pressure, pronounced constipation, etc. are possible.

Long acting neuroleptics

New possibilities in helping people with schizophrenia are opened by antipsychotic drugs-prolongs. These are ampouled forms of neuroleptics for intramuscular injections. The introduction into the muscle of an antipsychotic dissolved in oil (for example, olive oil) makes it possible to achieve its long-term stable concentration in the blood. Being absorbed into the blood gradually, the drug exerts its effect within 2-4 weeks.

Currently, the choice of long-acting antipsychotics is quite wide. These are moditen-depot, haloperidol-decanoate, clopixol-depot (and prolong clopixol, but 3-day duration of action, clopixol-acufaz), fluanxol-depot, rispolept-consta.

Carrying out antipsychotic therapy with long-acting drugs is convenient because the patient does not need to constantly remember the need to take them. Only some patients are forced to take correctors of side extrapyramidal effects. Undoubtedly, the advantages of such antipsychotics in the treatment of patients in whom, when drugs are discontinued or the concentration of the drug in the blood necessary for them, the understanding of the morbidity of their condition is quickly lost and they refuse treatment. Such situations often lead to a sharp exacerbation of the disease and hospitalization.

Noting the possibility of long-acting antipsychotics, one cannot but mention the increased risk of developing extrapyramidal side effects when they are used. This is due, firstly, to the large amplitude of fluctuations in the concentration of the drug in the blood during the period between injections compared with taking antipsychotic tablets, and secondly, to the inability to “cancel” the drug already introduced into the body with individual hypersensitivity to its side effects. in a particular patient. In the latter case, one has to wait until the prolongation drug is gradually, over several weeks, removed from the body. It is important to keep in mind that of the long-acting antipsychotics listed above, only rispolept-consta is atypical.

Rules for conducting therapy with neuroleptics

An important question is about the treatment regimen with antipsychotics: for how long, intermittently or continuously, should they be used?

It should be emphasized once again that the need for therapy with neuroleptics in people suffering from schizophrenia or schizoaffective psychosis is determined by the biological characteristics of the brain. According to modern data from the biological direction of scientific research on schizophrenia, these features are determined by the structure and functioning of the dopamine system of the brain, its excessive activity. This creates a biological basis for the distortion of the selection and processing of information and, as a result, for the increased vulnerability of such people to stressful events. Antipsychotics that normalize the work of the dopamine system of nerve cells in the brain, i.e. affecting the basic biological mechanism of the disease, represent a means of pathogenetic treatment

The appointment of antipsychotics is, of course, indicated in the active period of a continuously ongoing disease (without remissions), and there is reason to set the patient up for a long - at least for the next few years - treatment with these drugs. Antipsychotics are also indicated during exacerbation of the disease in the case of its paroxysmal course. In the latter situation, it must be borne in mind that the average duration of the exacerbation period in schizophrenia is 18 months. All this time, the readiness of the symptomatology, which “left” under the influence of treatment, remains ready to resume when the neuroleptic is canceled. This means that even if the symptoms of the disease have disappeared after a month from the start of therapy, it should not be stopped. Studies show that by the end of the first year after the withdrawal of antipsychotics, 85% of people with schizophrenia, the symptoms resume, i.e. aggravation of the disease occurs and, as a rule, there is a need for hospitalization. Premature cessation of antipsychotic therapy, especially after the first attack, worsens the overall prognosis of the disease, because. an almost inevitable exacerbation of symptoms for a long time disables the patient from social activity, assigns him the role of "sick", contributing to his maladjustment. With the onset of remission (significant weakening or complete disappearance of the symptoms of the disease), the dose of antipsychotics is gradually reduced to the level necessary to maintain a stable state.

Carrying out maintenance therapy is not always perceived by patients and their relatives as necessary. Often, the stability of well-being forms an erroneous opinion that the long-awaited well-being has come and the disease will not recur, therefore, why continue treatment?

Despite the well-being achieved, a person suffering from schizophrenia or schizoaffective psychosis retains a feature of the functioning of the brain in the form of excessive activity of the dopamine neurotransmitter system, as well as increased vulnerability to stressful influences and readiness for the development of painful symptoms. Therefore, taking maintenance doses of an antipsychotic should be considered as replenishing the deficiency of a certain substance in the body, without which it cannot function at a healthy level.

To help the person suffering from schizophrenia rethink the intake of maintenance doses of antipsychotics and other necessary medications, the help of specialists is required, which will be discussed in the next lecture. No less important, and sometimes paramount, are the understanding and support of his close people. Knowledge of the mechanisms of the development of the disease, the essence of the proposed assistance will help him gain more confidence.