New possibilities for treating mentally ill patients (review of foreign literature)

Clopixol (zuclopentixol), which has rightfully become a classic first-line neuroleptic for foreign specialists, is one of the newest and least studied drugs for the majority of domestic psychiatrists. At the same time, both a kind of spectrum of psychotropic activity of Clopixol, which combines a pronounced antipsychotic effect with a transient sedative and specific inhibitory effect, is of great interest, as well as the existence of various dosage forms of the drug, among which, along with the already familiar tablets and depot injections, there is a unique one that does not have analogs injectable form with three-day action (Klopiksol-Akufaz).

Zuclopenthixol is a powerful antipsychotic agent from the thioxanthene group containing a piperazine side chain. Zuclopenthixol is the cis isomer of clopixol and, as an active molecule, is included in all dosage forms of Clopixol.

The primary antipsychotic activity of zuclopenthixol, like most antipsychotics, may be due to its high affinity for dopamine D2 receptors. In addition, a relatively high degree of affinity of zuclopenthixol to dopamine D1 receptors was revealed, which probably determines the low severity of extrapyramidal disorders. Found also the affinity of zuclopenthixol for serotonin 5-HT2 receptors and a1 – adrenergic receptors.

In our opinion, the availability of a wide range of different dosage forms of the antipsychotic zuclopenthixol is an important advantage, since it opens up new therapeutic possibilities, allowing you to combine different doses, intervals and methods of drug administration in the same patient. In addition to this, the monotherapy method significantly increases the efficacy and safety of treatment by eliminating the possibility of mutual inhibition or potentiation of medicinal substances and their metabolites.

It is well known that at various stages of mental illness, the requirements for the selection of therapy are determined by the characteristics of a particular condition. As clinical experience shows, the optimal method of therapy for acute psychotic conditions may be the appointment of intramuscular injections of aqueous solutions of highly potent antipsychotics. This method provides a rapid therapeutic effect by eliminating the phase of hepatic metabolism, and also creates an optimal dosage control regimen. Unfortunately, the appointment of frequent intramuscular injections in the first days of a patient’s stay in a psychiatric clinic often leads to serious difficulties in the patient’s relationship with medical personnel, and also causes the formation of painful infiltrates at the injection site. In this situation, the advantages of the dosage form of the drug (Klopixol – Akufaz) with a fairly rapid development of sedative and antipsychotic action, but allowing for less frequent prescription, are undoubted.

Studies show that about 50% of people with schizophrenia do not take the prescribed treatment, which leads to a decrease in its effectiveness and an increase in the risk of relapse. In one of the latest works on this problem, more pessimistic figures are given: about 80% of patients with schizophrenia do not really take drugs. In this regard, the advantage of using depot neuroleptics, in particular Klopiksol Depo, is obvious and is associated with the convenience of administration (once every 2-4 weeks), the guaranteed intake of the neuroleptic into the patient’s body, a decrease in the risk of overdose of the drug when it is used independently by patients, as well as a decrease in the total dose of the drug, since when using depot neuroleptics there is no phase of hepatic metabolism. The last circumstance, i.e. a decrease in the total dose of the drug leads to less severity of side effects.

The use of depot preparations provides the most stable serum level of the active agent and a more predictable antipsychotic effect. In addition, the use of depot neuroleptics contributes to better socialization of patients, because eliminates the need for regular medication during business hours, which may be undesirable or inconvenient for patients.

It seems quite logical to present the literature data on the use of various dosage forms of Clopixol in the distribution according to the “longitudinal” disease, ranging from the most acute and severe conditions (manifestation, exacerbation of psychosis), requiring active therapeutic intervention, to lighter ones (the formation of remission, remission, mild processes), where supportive therapy is needed.
Clopixol Akufaz (zuclopenthixol acetate) is an injection with a duration of 48-72 hours for intramuscular administration.

This dosage form of Clopixol was specially developed at the request of Scandinavian psychiatrists for the relief of acute psychoses. The acetate, which is the ester of zuclopenthixol, is dissolved in coconut oil. After intramuscular administration, the acetate undergoes hydrolysis with a gradual release of the active molecule zuclopenthixol. The concentration of zuclopenthixol in plasma increases rather quickly, its maximum falls on a period of 24 to 48 hours (on average 36 hours) after injection, followed by a gradual decrease by 3 to 4 days.

Biological studies have shown that the maximum concentration of the drug in serum was observed in the range from 28 to 56 hours. The authors came to the conclusion that the introduction of clinical doses (50-150 mg) of Clopixol Akufaz should lead to an even faster introduction of the drug into dopamine structures, persistent preservation of the required parameters in the established dose interval and, possibly, an extension of this period.

The experience of using Klopixol Akufaz in a clinical setting has confirmed the above theoretical and preclinical data on the features of its therapeutic action in acute psychotic conditions with a fairly good tolerance. According to the majority of researchers, Clopixol Akufaz provides reliable control over the mental state at the earliest stages of the development of acute mental disorders, including their manifestation or exacerbation of chronic mental illness. The dynamics of the clinical state after the first intramuscular injection of Klopixol Akufaz was very pronounced and consisted in a rapid and stable reduction in acute manifestations of mental disorder.

The efficacy and safety of Clopixol Akufaz have been established in a number of multicenter studies. In most of them, the drug was used to treat 3 types of acute psychotic disorders (according to DSM III criteria):
for the first time in life, an acute psychotic episode developed (assessed in the framework of schizophrenia)
exacerbation of a chronic schizophrenic disorder
manic phase of TIR

Doses of the drug ranged from 25 mg to 250 mg of zuclopenthixol acetate per injection and varied depending on the therapeutic need and individual patient tolerance of the drug. It should be noted that in most cases, doses were used that did not exceed 150 mg of zuclopenthixol per injection, with the most often recommended dose of 100 mg. Most studies used 1 to 3 injections with an injection interval of 24 to 96 hours. Most often, 2-3 injections were prescribed, although in some studies, significant improvement was achieved with a single injection. The expediency of using more injections of Klopixol Akufaz is questionable due to the decrease in its nonspecific sedative effect over time (see below). Concomitant therapy in all studies was limited to the use of antiparkinsonian drugs (only in cases where such a need arose), hypnotics, tranquilizers, and in some patients – lithium preparations.
Sedative action

It should be noted that the first reaction to Klopixol Akufaz is associated with the presence of a powerful nonspecific transient sedative effect that develops in the first hours after injection in the absence of a hypnotic effect. The sedative effect of Clopixol Akufaz was clearly manifested already 2 hours after injection, reached a maximum by 8 hours, and then gradually decreased. By the power of sedative action, Clopixol Akufaz is superior to haloperidol. After the second injection, the severity of sedation is usually less than after the first.
Antipsychotic action

In most studies, a clear antipsychotic effect of the drug was recorded by 24 hours, with a subsequent increase by 72 hours after injection. In some studies, a statistically significant antipsychotic effect of Clopixol Akufaz was determined as early as 8 hours after the start of treatment. In most patients, the observed therapeutic effect, assessed using the BPRS (Brief Psychiatric Rating Scale) and CGI (Clinical General Impression Scale), was classified as significant or pronounced. So, 72 hours after the first injection of Klopixol Akufaz (50-200 mg), a significant improvement was determined in 88% of patients with acute psychoses. In terms of the strength of the antipsychotic effect and the rapidity of the development of the therapeutic effect, this dosage form of Clopixol is comparable to injectable haloperidol.

Noteworthy is the fact that the use of Clopixol Akufaz led to significant changes not only in the total average BPRS scale, but also in individual indicators characterizing the severity of independent psychopathological symptoms. At the same time, according to some indicators, such as “fencing off”, “tension”, “suspicion”, “hallucinatory behavior”, “unusual content of thoughts”, “reduced affect” and “agitation” – a statistically significant effect appeared already by 8 hours after the injection … In a number of studies, a distinct effect was found not only on productive, but also on negative schizophrenic symptoms.

The features of changes in BPRS indicators described above during therapy with Klopixol Akufaz are of great importance, since they indicate the so-called. The “uniform” nature of the antipsychotic action of the drug, which covers both traditional “productive” (hallucinations, delusions, agitation) and “negative” (emotional and social isolation, mannerisms, etc.), and affective disorders.

This feature of the drug’s action, as well as the significant severity of the therapeutic effect, undoubtedly allow it to be classified as one of the most active antipsychotics.
Anti-manic action

The action of Klopixol Akufaz has been studied in patients with acute manic conditions. The mental state of patients was assessed using the BRMS (Beck-Raphaelsen scale for assessing manic disorders) and CGI scales. On the BRMS scale, there was a statistically significant (p <0.01) decrease in the overall score (reflecting the severity of mania) already 24 hours after injection. In general, responders (i.e. patients with marked improvement) make up about 80%.

In a multicenter, randomized trial, the effect of Clopixol Akufaz and injectable haloperidol on acute psychotic conditions, including mania, was compared. It was found that the anti-manic effect of Clopixol Akufaz appears faster than that of haloperidol. The reduction in mania (according to BRMS) 24 hours after the start of treatment was more significant in the group receiving Clopixol Akufaz than among those receiving haloperidol. A more pronounced antimanic effect of Clopixol Akufaz compared with haloperidol was also recorded 3 days after the first injection.
Anti-aggressive action

In a number of works it was noted that such a symptom as “aggressiveness” was subjected to a particularly pronounced reduction. Thus, the results of counting the number of acts of aggression by patients in a psychiatric hospital over several years are presented. It was found that the number of cases of aggression within a year after the start of the use of Klopixol Akufaz in this clinic has decreased by about half, compared with the previous year.

The use of Clopixol Akufaz, on the one hand, leads to a decrease in the aggressiveness of patients due to the general antipsychotic effect of the drug. On the other hand, one should not underestimate the fact that the use of a drug prescribed in the form of an injection only 1 time within 2 to 3 days, in comparison with water-soluble injections of traditional antipsychotics prescribed 3 to 4 times a day, reduces the very possibility of provoking aggression from the patient and improves compliance (ie, patient consent to treatment). The authors conclude that Clopixol Akufaz is “a unique first-line antipsychotic drug for the treatment of patients with a high potential risk of aggressive and hostile behavior”.

Several authors have studied the effect of Clopixol Akufaz on “psychotic anxiety.” An open-label study was conducted using a special Psychotic Anxiety Scale (PAS, O. Blin et al, 1988). Forty-six patients with schizophrenia and “short psychotic disorder” were prescribed Clopixol Akufaz. In most cases, the course of treatment consisted of three injections, which were given once every three days. The average dosage of the drug was 126 – 138 mg per injection. A statistically significant decrease in anxiety was noted as early as 24 hours after the first injection. By the end of the course of treatment, i.e. by day 9, anxiety had disappeared completely, which correlated with a significant overall reduction in psychotic symptoms.
Side effects

The frequency of side effects when using Klopixol Akufaz, according to most authors, was small with a low and medium degree of their severity, which is probably due to the pharmacokinetic characteristics of the drug, which determines a relatively gradual increase in its plasma level. In 43% – 80% of patients in the studied groups, side effects were not observed or, being mild, did not disrupt the general life of the patients. One study [18] found that 52% of patients had no side effects at all. At the same time, there is evidence that when using Clopixol Akufaz (up to 200 mg per injection) with a high therapeutic effect (79% of responders), acute dystonic reactions of significant severity were observed in 12% of cases, requiring the appointment of antiparkinsonian drugs.

Side effects in the studies were assessed using the CGI, ESRS (Extrapyramidal Symptom Scale) and UKU (Scandinavian Side Effect Scale) rating scales. In most cases, side effects developed 24 to 72 hours after the first injection. Tremor was one of the most common side effects. Along with it, sweating, restlessness, dizziness, drowsiness, and dry mouth were noted. The most pronounced and influencing the level of adaptation are neurological side effects in the form of dystonia, rigidity, akinesia, tremor and akathisia. Of autonomic disorders, accommodation disorder and increased salivation were most often noted. At the same time, there is evidence that side effects had a certain dynamics during the 3-day period after the first injection. So, it is indicated that such side effects as tremors, sweating and restlessness tended to weaken, and such as dizziness, drowsiness, dry mouth, increased sleep duration and nasal congestion, to increase. At the same time, the percentage of patients with severe side effects that disrupted daily functioning decreased from 22.2% to 7.4%. Comparison of Clopixol Akuphaz and injectable haloperidol revealed a greater severity of extrapyramidal side effects in the latter, while the difference was statistically significant.

Concomitant treatment associated with the need to correct the side effects of therapy according to various data, was used in 14 – 54% of patients.

When analyzing the use of injectable forms of antipsychotics, the problem of tissue damage at the injection site deserves a separate consideration. Specially conducted comparative studies on animals have shown that water-soluble antipsychotics cause necrotic tissue damage at the injection site, while injections based on Viscoleo oil used in Clopixol Akufaz do not lead to local damage. In clinical practice, this property of the drug leads to the absence of local irritating effects.
Laboratory research

The results of laboratory studies carried out in the course of therapy with Klopixol Akufaz showed that only a small number of laboratory parameters in all examined groups of patients went beyond the normal range both at the beginning and at the end of therapy, while the frequency of cases was not higher than expected for the corresponding group [3 ]. No significant changes in laboratory parameters during the course of therapy were identified.
Clopixol Tablets (Zuclopenthixol Hydrochloride) – Oral Form

This form of the drug has a much longer history of use than Clopixol Akufaz and is widely used worldwide for the treatment of schizophrenia and other mental illnesses.

To date, a large amount of information has been accumulated about the experience of using zuclopenthixol in tablets in the treatment of acute psychoses, exacerbations of chronic psychosis and acute manic states. Many direct and comparative, including double-blind, trials of this drug have been carried out, confirming its high therapeutic efficacy, comparable to the efficacy of haloperidol and chlorpromazine.

In the UK, a multicenter study compared, using a double-blind method, the effect of tablets of Clopixol and chlorpromazine in acute psychoses (schizophrenia and schizoaffective psychosis). The study included patients aged 18 to 65 years who began to receive Clopixol 25-150 mg / day (average 75 mg / day) or chlorpromazine 100-600 mg / day. Starting from the second week of treatment, in most patients, without prejudice to the therapeutic effect, the daily dose of Clopixol was reduced to 50 mg. Chlorpromazine was used throughout the study (10 weeks) mainly at a dose of 600 mg / day. Both drugs have shown high antipsychotic activity. According to this indicator, there was a tendency towards the advantage of Clopixol, however, it did not reach the degree of statistical reliability.

Another multicenter, double-blind study compared the effects of clopixol and haloperidol tablets on acute psychoses. The average daily dose of Clopixol was 33.5 mg, and that of haloperidol was 10.3 mg. Both drugs showed equally high therapeutic activity, however, patients taking Clopixol were discharged from the psychiatric hospital earlier, which reflected the faster development of the antipsychotic effect of Clopixol compared to haloperidol. Clopixol caused a significantly more pronounced reduction in the anxiety-depressive component of psychosis than haloperidol. In addition, the extrapyramidal symptoms in those taking Clopixol were, as a rule, transient, while in patients receiving haloperidol, they were almost constant.

Significant improvement while taking Clopixol tablets was observed in 69 – 87% of patients with acute and subacute manic conditions. A significant mitigation of acute manifestations of manic disorder was observed according to various data during the first 1 to 4 weeks of therapy. In some studies in some of the most severe cases, the treatment of an acute condition began with the use of Clopixol Akufaz during the first 3 to 6 days of treatment, and then continued with Clopixol tablets. It is important to pay attention to the fact that the use of high doses (up to 130 – 150 mg / day) was not more effective than the use of average therapeutic doses for manias (20 – 50 mg / day). About 80% of patients received the drug at a dose of 20-30 mg / day, and an increase in dosages above 50 mg / day did not increase the effectiveness of therapy, but only led to an increase in the severity of side effects. Most researchers have come to the conclusion that with a good therapeutic effect, it is possible to start reducing doses on average 2 weeks after starting treatment without the risk of exacerbation. It has been argued that slightly lower doses are needed to treat manias than to treat schizophrenia.

Of particular interest is the use of Clopixol for agitation and aggressiveness in the elderly. Clopixol was compared using a double-blind method with thioridazine and a combination of haloperidol and levomepromazine. Both studies were conducted in Scandinavia and were multicenter. The first of them included dementia patients (mainly with Alzheimer’s disease) at the age of 64–97 years who were in the hospital. Their mental state was characterized by “the presence of anxiety, hostility, as well as accompanying anxiety, confusion, irritability, insomnia, delirium, hallucinations, hypochondria, and screaming.” A higher efficacy of Clopixol on insomnia was found (the difference between the drugs is statistically significant). Side effects of Clopixol were rare, their severity was insignificant, and there was no serious undesirable effect on the cardiovascular system associated with the drug.

A population of patients similar in demographic and clinical characteristics was used when comparing Clopixol tablets with a combination of haloperidol and levomepromazine (tizercin, nosinan). The study lasted 4 weeks. The starting dose for Clopixol was 4 mg (one 2 mg tablet twice a day). In another group of patients, 1 mg of haloperidol was administered in the morning and 5 mg of levomepromazine in the evening. Average daily doses of drugs at the end of the study were slightly higher: 4.8 mg of clopixol; 1.6 mg haloperidol + 7.6 mg levomepromazine. The authors concluded that for the treatment of aggressiveness and agitation in the elderly, it is preferable to use Clopixol tablets, since it acts faster and allows monotherapy.

It should be noted that, in accordance with the average dosages used in a particular mental pathology, tablets of different dosages are produced: 2, 10 and 25 mg, which makes the use of the drug more convenient.

Thus, literature data indicate that Klopixol tablets can be successfully used both in the treatment of acute and subacute psychoses, including acute manic states, and in agitation and aggression in the elderly, as well as for the correction of behavioral disorders in persons with intellectual disabilities. …
Clopixol Depot is an oily solution of zuclopenthixol decanoate for intramuscular administration with a duration of action of one injection from 2 to 4 weeks.

Clopixol Depo is widely used in psychiatric practice, primarily as a means of supporting outpatient therapy for patients with schizophrenia. In some research, it has been used for active treatment of schizophrenia in a hospital. Finally, depot injections of zuclopenthixol have been used to treat psychotic disorders associated with behavioral disorders in the elderly and conduct disorders in intellectually impaired individuals.

When switching from the tablet form of Clopixol to taking Clopixol Depot, the general rule applies: the dose of the depot injection is calculated by multiplying the daily oral dose by 8. Subsequently, a 2-week interval between injections is usually maintained. When switching from Klopixol Akufaz to treatment with Klopixol Depo, 200-400 mg of Klopixol Depo should be administered intramuscularly simultaneously with the last injection of Klopixol Akufaz. Further, repeated injections of Klopiksol Depot are carried out once every 2 weeks.

There have been several studies of zuclopenthixol decanoate in which it was compared with other depot neuroleptics using a double-blind method and showed high therapeutic activity. One of these studies, which examined Clopixol Depot and haloperidol decanoate, was conducted as a multicenter study in Finland and Sweden. The study included middle-aged patients (25-60 years old) diagnosed with chronic schizophrenia (according to DSM-III) in the stage of stabilization. During the study, patients received injections of both depot antipsychotics every 4 weeks during the 9-month treatment period. The authors considered a dose of 200 mg of zuclopenthixol decanoate to be equivalent to 50 mg of haloperidol decanoate. The patient’s condition and its dynamics were assessed using the CGI, BPRS, UKU and SAS (Simpson-Angus Scale for Evaluation of Extrapyramidal Disorders) scales. The average doses used were 284 mg (100 to 600) Clopixol Depot and 92 mg (38 to 200) haloperidol decanoate. Both drugs in the course of the study showed equally high therapeutic activity; the total scores of the rating scales reflecting the severity of psychopathological disorders progressively decreased throughout the study, despite the fact that they were not initially high, because the patients were already in the stabilization phase.

In “chronic schizophrenia,” the systematic use of Klopixol Depo contributed to the reduction of both the overall BPRS score, which reflects the severity of the condition, and indicators for individual symptoms (hallucinations, delirium, depression, aggressive behavior). The effect of Clopixol Depo on negative schizophrenic symptoms was also noted.

Of undoubted interest are the results of the use of zuclopenthixol decanoate in the treatment of patients with schizophrenia in a hospital. If two foreign works dealt with “chronic paranoid schizophrenia”, then in one of the few domestic studies (G. Ya. Avrutskiy), Klopixol Depo influenced acute schizophrenic psychoses. Inpatient doses (up to 1000-1200 mg) were generally higher than those used in outpatient practice (200-400 mg), and the interval between injections was shorter (up to 1 week). In all these studies, Clopixol Depot showed high antipsychotic activity with a low severity of side effects. In one of the works, paranoid schizophrenia was recognized as the “best indication” for the drug. In a domestic study, Clopixol Depot surpassed haloperidol decanoate, moditen depot, and piportil L4 in terms of therapeutic efficacy [1].

Despite the long history of the use of deposited antipsychotic drugs, only a relatively small part of the research is devoted to the targeted study of the characteristics of their use in later life. The problem of treating elderly patients with symptoms of excitement (late paraphrenia, organic psychosis in dementia) with Clopixol Depo has been studied in the UK. The study, 24 weeks long, was carried out in an open way, it included 30 patients aged 65 years and older. To assess their condition, the following scales were used: BPRS, CGI, etc. Most of the patients received injections of zuclopenthixol decanoate at a dose of 50 mg (maximum 200 mg) every 2 to 4 weeks, which corresponded to 4 to 6 mg / day with daily oral administration. The results of the study showed that an improvement in the mental state was noted already after 3 weeks of treatment, which was expressed in a statistically significant (p <0.01) decrease in the total BPRS score, as well as indicators: “anxiety”, “thought disorder”, “agitation” and ” suspicion”. Side effects were rated in 4 categories: behavioral, extrapyramidal, autonomic, and allergic. The initial level of side effects in most patients was determined by the fact that before the appointment of depot – injections of Clopixol, they took other antipsychotics. Compared to baseline, there was a clear decrease in behavioral side effects during treatment with Clopixol Depo, other side effects did not undergo significant changes. Insomnia, stiffness and tremors were the most common. In 25% of patients, there were no side effects, while in the rest, the violations did not have any significant effect on the quality of life and adaptation. In 30% of cases, patients did not require concomitant treatment at all. Antiparkinsonian medications were used in 50% of patients and the researchers consider this to be acceptable, provided that such prescriptions should not be routine practice. In the future, the dosage of antiparkinsonian drugs was reduced by adjusting the dose of the neuroleptic.

Clopixol Depo has also shown itself to be effective in the treatment of behavioral disorders in persons with intellectual disabilities, while the side effects of the drug did not cause serious problems and did not interfere with treatment.
Selection of the optimal dose of Clopixol Depot

One of the most important tasks of psychopharmacotherapy is the choice of the optimal dose of the drug, i.e. dose that provides the maximum therapeutic effect with a minimum of side effects. In the chronic phase of the disease, this is achieved by using the minimum effective dose (MED), which is necessary to prevent the development of a relapse of the disease.

In Denmark, a study was conducted to determine the MED of zuclopenthixol decanoate and blood levels of the drug in the maintenance treatment of chronic schizophrenia. The MED averaged 200 mg zuclopenthixol decanoate every two weeks (60 to 400 mg) in the study. A statistically significant positive correlation was found between MED and corresponding serum drug levels. Achieving MED by gradually decreasing the dosage, according to the authors, can be not only a research task, but also be one of the aspects of the work of a practitioner, provided the minimum effective dose is correctly and carefully selected.
Co-injection of Clopixol Akufaz and Clopixol Depot

A significant part of patients with exacerbation of chronic psychosis (most often schizophrenia), which is stopped by Clopixol Akufaz, then needs long-term supportive treatment. Taking into account the pharmacokinetic characteristics and features of the clinical action of Clopixol Akufaz and Clopixol Depo, their joint administration in one syringe seems logical. The relief of acute manifestations of psychosis is carried out by Klopixol Akufaz, and by the time its effect is exhausted (4-5 days), Klopiksol Depot begins to act.

The theoretical prerequisites for the use of co-injection have been verified in clinical trials. In total, these studies involved 22 patients with exacerbation of psychosis (of which 18 patients with schizophrenia). In most cases, the first co-injection consisted of 100 mg of Clopixol Akufaz and 200 mg of Clopixol Depot. The duration of the first study was limited to 2 weeks; all patients received only one co-injection. A significant reduction in psychopathological disorders was observed, which was reflected in a decrease in the scores of the rating scales 1 and 2 weeks after co-injection, i.e. it was about a continuous 2-week therapeutic effect on psychosis. The protocol of the second study (10 patients with schizophrenia participated) was more complicated, it was allowed to use additional injections of Clopixol Akufaz (50-150 mg each) on days 3 or 7 after co-injection, 14 and 28 days after co-injection, repeated injections of Clopixol Depot were made (200 – 350 mg). A pronounced improvement in the condition was recorded as early as 3 days after the start of treatment (25% decrease in the total BPRS score, p <0.001). In the future, the condition continued to improve, by the end of 4 weeks, the reduction in the total BPRS score was more than 50%. Data on the side effects of such neuroleptic treatment are of considerable interest. The authors of the work concluded that, in general, side effects were quite rare, their severity, as a rule, was not significant. In one of the patients, on the second day after co-injection, acute dystonic reactions were observed, which required parenteral administration of antiparkinsonian drugs. In another case, dystonia, rigidity, hypokinesia, orthostatic dizziness were noted. One of the patients developed mild orthostatic dizziness on the 14th day after the start of treatment. Against the background of the use of correctors, the side effects disappeared completely, in none of the cases did they lead to the cancellation of Clopixol therapy. After the studies carried out, the method of treating psychosis by co-injection has become routinely used in a number of foreign psychiatric clinics.

Analysis of this literature review devoted to the experience of using various dosage forms of zuclopenthixol allows us to draw the following main conclusions:
The availability of a wide range of dosage forms of zuclopenthixol provides an optimal approach to the treatment of various forms of mental disorders at various stages of the disease.
Zuclopenthixol, especially in the form of Clopixol Akufaz, effectively relieves acute psychoses, including manic states and exacerbations of chronic psychosis, has high therapeutic activity against the most severe psychotic disorders, such as delusions, hallucinations, thought disorders, psychomotor agitation, aggressiveness, etc.
High therapeutic the effect of zuclopenthixol is combined with the safety of its use, associated with a low frequency and low severity of side effects.
The use of Clopixol Akufaz and co-injections of Clopixol Akufaz and Clopixol Depot, in fact, is a new approach to the treatment of acute psychoses.
The possibility of a relatively rare appointment of Klopiksol Akufaz (1 time in 2-3 days) provides a more humane and comfortable treatment of acute psychoses, reduces the risk of developing conflicts between the patient and the medical staff.
The presence of various dosage forms of zuclopenthixol makes it possible to carry out monotherapy – from the use of Clopixol Akuphaz in the acute period of the disease, to continuing treatment of the patient at the stage of convalescence, and then maintenance therapy with tablets or depot injections of Clopixol containing the same active substance (zuclopentixol). Monotherapy throughout the course of the disease provides the best therapeutic effect with a minimum of adverse events.

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