RU2452486C1 - Method of pharmacotherapy of panic disorder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely psychiatry. A method of treating panic disorder involves prescribing psychopharmacotherapy; if diagnosing panic disorder, the patient is simultaneously prescribed with clonazepam 2 mg a day and etifoxine 1 capsule 3 times a day; maximally early dopamine excretion follows; the length of clonazepam therapy makes 2 weeks, then the dose is decreased by 25 % a week with the etifoxine dose being unchanged; if observing the improvement, decreasing the dose results in clonazepam withdrawal; exacerbation requires prescribing the previous dose of clonazepam with adding a neuroleptic in case of detecting paraclinically increased daily dopamine excretion; 2 weeks after observing the stabilisation, attempted clonazepam withdrawal is repeated; after clonazepam withdrawal, the therapy is continued with using etifoxine and a a neuroleptic in case of detecting daily dopamine excretion; the preparations are gradually withdrawn starting from the 3^rd month after the last panic attack.

EFFECT: invention enables substantially increasing effectiveness and safety of therapy of panic disorders.

Description

The invention relates to medicine, namely to psychiatry, and can be used in the treatment of patients suffering from panic disorder (PR).

A high prevalence of PR is known: up to 3.6% of the population (Perkonigg A., Wittshen H.U., 1995). Among patients who turned to psychiatrists, every 10-20 patient has a diagnosis of PR (Vorobyeva O.V., 2009). The treatment of panic disorder is a very difficult and crucial task. It is complicated by the pronounced tendency of the disorder to chronicity and relapse: exacerbations within 2 years occur in 30% of patients (Wayne A.M., 1998). Chronification of PR is facilitated by inadequate and untimely therapeutic measures. Anxiety disorders, including panic disorder, are diagnosed in only 50% of patients with obvious symptoms. Less than 50% of patients receive any treatment and less than 30% receive adequate therapy (Vorobyeva O.V., 2009).

To date, a rather large amount of information about PR therapy has been accumulated. Recommendations on the use of psychopharmacotherapy (using benzodiazepine tranquilizers, antidepressants, normotimics, atypical antipsychotics, etc.) and psychotherapy are widely presented in the literature. At the same time, this experience remains unsystematic, devoid of algorithm harmony, which complicates its practical use. One of the significant problems is the increased use of antidepressants (although depression does not occur in all, but in 56-65% of people suffering from panic attacks: Danilov AB, 2010), which is not always justified and conceals the risk of pathomorphism of the disorder and the subsequent, artificially induced , development of affective states. The problem is also the long-term use of benzodiazepine tranquilizers, which have the potential to form dependence (Mosolov S.N., 2005).

Thus, the problem of treating PR is an everyday reality of medical practice; Despite the abundance of scientific information, the doctor has to constantly look for ways and solutions.

The well-known "Method for the treatment of panic disorder" (Vorobyova OV Panic attacks: clinic, diagnosis, treatment principles. M., 2009. 46 p.).

The author offers a standard of care for PR: long-term appointment (several months) of an antidepressant from the SSRI group; the addition of a benzodiazepine drug during the initial 6–8 weeks of treatment as an effective “bridge” until the desired SSRI effect is realized.

The disadvantages of this method is the blurring of the selection criteria of psychopharmacotherapy; in fact, an unambiguous requirement for the appointment of antidepressants; prolonged use of tranquilizers with a risk of addiction.

The well-known "Method for the treatment of panic disorders" (Baranov P.A. 2010. http://www.pan-at.com/stati/stati24.htm).

The essence of the method is the use of the following anti-panic agents: antidepressants and the so-called atypical benzodiazepines (alprazolam and clonazepam). These basic tools are combined with antipsychotics if necessary, "act on psychopathic (most often hysterical) and overvalued (hypochondriacal) disorders", as well as "in the diagnosis of schizophrenic process."

The disadvantages of the method are identical to those indicated for the previous method of treatment.

The well-known "Method for the treatment of panic disorder" (Wayne A.M., Vorobyova OV Neurophysiological model of "paroxysmal brain." Vestnik AMN. M: Medicine, 1998. S. 32-36), we have chosen as a prototype. The method provides for the implementation of the following principles:

1. The course of treatment is long, up to 1 year, with the obligatory very careful gradual withdrawal of drugs.

2. The essence of treatment is to prevent attacks.

3. Typical benzodiazepines are most suitable for stopping crises, and antidepressants (at least 4-6 months) are most effective in preventing crises:

- TCA: anafranil, melipramine, amitriptyline. Their use is especially effective if PR is combined with a distinct depression. Start with small doses (25 mg / day), build up slowly. Disadvantages - delayed effect and an abundance of side effects.

- SSRIs: fluoxetine, fevarin, zoloft, citalopram. Disadvantages - exacerbation at the beginning of therapy (hyperstimulation and paradoxical increase in anxiety).

- IMAO (little studied).

When choosing between antidepressants and atypical benzodiazepines, you can use the following rule: the more pronounced the phobic and obsessive component, the better the effect can be expected from antidepressants. On the contrary, with the prevalence of autonomic and somatoform manifestations in the clinical picture of panic disorder, atypical benzodiazepines are the means of choice.

4. Treatment with any drugs should be started with small doses, gradually increasing.

5. It is advisable to use stabilizers of the sympathetic and parasympathetic systems in therapy.

6. When combined with allergic manifestations, the use of desensitizing agents (calcium preparations, ascorbic acid, tavegil) is necessary.

7. In the case of severe hyperventilation disorders at the time of the crisis - breathing in the bag, which reduces the severity of hypocapnia and reduces the severity of symptoms caused by respiratory alkalosis.

8. Therapeutic gymnastics, massage, balneotherapy.

9. When the first effect is achieved - a decrease in severity and the disappearance of crises - the role of psychotherapy increases. The goal is to expand the regime and return to previous professional occupations.

10. The beginning of the gradual withdrawal of drugs - usually after a few weeks of full health.

The disadvantages of the described method of treating PR again include the unambiguous prescription of antidepressants and the indefinite duration of therapy with benzodiazepine tranquilizers.

Our negative assessment of the mandatory and indiscriminate administration of antidepressants to patients with PR is also confirmed by the study of 10-year results of treatment of patients by Steven E. Bruce, Ph.D .; Russel G. Vasile, M.D .; Robert M. Goisman, M.D. et al. (Am. J. of Psychiatry 2003; 160: 1432-1438). The authors convincingly demonstrated the absence of the benefits of a clear transition to antidepressants as the base class of treatment for PR.

We have not found any analogues of the method we use, providing for a differentiated, based on the pathogenetic approach, psychopharmacotherapy of PR, in the available literature.

The aim of the invention is to increase the effectiveness and safety of treatment of PR.

This goal is achieved by the fact that when the diagnosis of Panic Disorder is established, the patient is simultaneously prescribed clonazepam at a dose of 2 mg per day and etifoxin 1 capsule 3 times a day, as soon as possible, a study of daily dopamine excretion is performed; the duration of clonazepam therapy is 2 weeks, then the dose begins to decrease by 25% per week, while the dose of etifoxin remains unchanged; with positive dynamics, a dose reduction results in the abolition of clonazepam, if an exacerbation occurs, the previous dose of clonazepam is prescribed and, in the case of a paraclinically detected increase in daily excretion of dopamine, an antipsychotic; 2 weeks after stabilization of the condition, the attempt to cancel clonazepam is repeated; after cancellation of clonazepam, therapy is continued with the use of etifoxin and, in the case of an identified increase in daily excretion of dopamine, an antipsychotic; gradual drug withdrawal begins 3 months after the last panic attack.

The invention "Method for the pharmacotherapy of panic disorder" is new, since it is not known in the field of medicine in the treatment of panic disorder.

The novelty of the invention lies in the fact that for the first time a technique has been proposed that reduces the risk of developing dependence on benzodiazepine tranquilizers, allowing a differentiated approach to the appointment of antipsychotics, which increases the effectiveness and safety of treatment of PR.

The invention "Method for the pharmacotherapy of panic disorder" is industrially applicable, as it can be used in health care, medical institutions of a psychiatric profile.

"The method of pharmacotherapy of panic disorder" is as follows.

When the diagnosis of Panic Disorder is established, the patient is simultaneously prescribed clonazepam at a dose of 2 mg per day and etifoxin (stresa), 1 capsule 3 times a day; at the earliest possible date, a biochemical study of daily dopamine excretion is performed. The duration of clonazepam therapy is 2 weeks, then the dose begins to decrease (by 25% per week), while the dose of etifoxin (stresis) remains unchanged. With positive dynamics, a dose reduction results in the abolition of clonazepam; the onset of exacerbation requires a return to the previous (to a decrease that led to an exacerbation) dose of clonazepam and the appointment of an antipsychotic (in the case of a paraclinical increase in daily excretion of dopamine). 2 weeks after stabilization, the attempt to withdraw clonazepam is repeated. After the cancellation of clonazepam, therapy continues with the use of etifoxin (stresam) and (in the case of an earlier paraclinically detected increase in daily excretion of dopamine) antipsychotic. The gradual withdrawal of drugs begins 3 months after the last panic attack, with the establishment of a stable remission.

An example of a specific application of the "Method of pharmacotherapy of panic disorder" in patients.

Patient B.D.A., history 49/09.

From the anamnesis: heredity on both lines is weighed down by alcohol abuse. The patient was born in 1972 from the fourth pregnancy, the second birth. Pregnancy proceeded without pathology, delivery on time, prompt (for 1-2 hours). Born mature, full-term. In growth and development did not lag behind; grew nimble, active, mobile, not painful.

When the patient was 2-3 years old, the parents divorced. The reason for the divorce was the drunkenness of his father. After 2 years, the mother remarried. Relations with the stepfather developed well; the patient willingly looked after his younger half-brother.

From the age of 4, he willingly attended kindergarten, adapted quite easily, although traits such as anxiety, suspiciousness, resentment, and vulnerability were noticeable to this age. These features were moderate and did not impede adaptation.

I went to school at the age of 7, studied well, giving a clear preference to humanitarian subjects. In the elementary grades of school, shyness and resentment became somewhat more noticeable. It was "a little chubby," and peer ridicule "hurt badly." With difficulty due to shyness, he answered at the blackboard; I felt more comfortable in the usual company.

In the summer of 84 g (12 years), the patient's stepfather suffered appendicitis complicated by peritonitis. Stories about the operation, the appearance of the sick stepfather, dressings at home made a painful impression on the patient. He became anxious, thought a lot on these topics, feared that he could also develop a similar disease. Against this background, pain began to arise in the right side, sharply increasing anxiety - I thought that he also develops appendicitis, imagined how “they will cut him”. They went to the surgeon several times, the condition improved somewhat after the doctor’s assurances that there was no surgical pathology. He became more attentive to food - he made sure that "there were no specks, hair, etc." in the food, because in his view, this could provoke appendicitis. All these manifestations disappeared in September of the same year, which is explained by the patient and his mother being busy with studies, communicating in the classroom, and switching attention.

In 1986 (14 years), the patient's older sister died in an accident. He reacted with a severe reaction of grief, the severity and duration of which corresponded to psychological laws.

Puberty - from the age of 15: there was an attraction, pollutions; started to shave. The period proceeded with noticeable reactions by groups, hobbies (the latter changed from introverted collecting in the pre-pubertal period to extrovert - discos, communication). Communication noticeably improved, easily found a common language with the girls. During the puberty, there was some dissatisfaction with his appearance, he thought about the scars on his face, his mood did not decrease significantly, there were no ideas of attitude, he did not develop plans for changing his appearance.

In 1989 (17 years old) he entered the Agricultural Institute with a degree in agronomy. Studying was relatively easy, I studied with interest, finding at the same time a lot of time for drinking alcohol in the company of other students. He graduated at the end of 1993, got a good job (good salary, position in the area, company car).

In the summer of 1994, he fell in love with a girl, believes that this was the first vivid feeling in his life. Relations ceased on her initiative, unexpectedly for the patient, in January 1995, He was very worried, could not come to terms with what had happened. At the same time, the patient’s mother developed appendicitis, after which there were similar experiences with the previous ones: there were alternating pains and discomfort in the abdomen, fear of inflammation and the upcoming operation. For the first time with good effect, on the advice of her mother, she began to use phenazepam occasionally.

At the same time, despite the worsening state of health, he continued to prepare for the ongoing competition for farm internships in Germany. The only one from the region passed the exam and on April 15, 1995 left Russia. The first trip abroad, the striking contrast of agriculture and the overall standard of living in another country, "distracted", reducing the severity of fear and pain. To return from such a business trip “it was accepted with the car”, so he worked tirelessly to save money; together with his comrade "refused himself everything." After a month and a half, "exhausted by such a life," they had a fight, in the fray, got a fracture of the index finger. Forced to be easy to work, loneliness (the comrade returned home after the incident) led to the resumption of anxiety, pessimistic thoughts about the girl who left her. At the same time, I experienced anxiety about “how the damaged finger will heal, whether surgery will be needed”, and discomfort in the abdomen. Stress relieved by taking phenazepam or alcohol. Having overcome the "temptation" to give up everything and return home, he was still able to continue working, as a result, he accumulated the necessary amount and bought a car.

Returning home with the car, he was worried about the dangers awaiting at the border (racketeering). Decided to go by ferry. On the road, he feared that the ferry would “crash”; that "they will deal with him." Frequent reflections on how an injured finger heals suddenly transformed into a powerful fear that it would hit his eye with that finger. The thought was "strange, frightening, without success I tried to drive it away." During an attack of panic, I felt a pronounced heartbeat, rapid breathing, a feeling of "unreality of what is happening."

Upon returning home, he looked exhausted, thin, anxious. As it turned out, a fracture of the finger did not grow together correctly, which required treatment and a course of rehabilitation. All attention was riveted to the finger, and panic attacks, accompanied by the thought that he would “break loose and hit himself in the eye”, arose quite often. After 2-3 weeks at home, the condition began to improve, activity increased, the frequency of panic attacks decreased. He began to make plans for a second trip to Germany for the next car (and fulfilled the plan at the end of the same, 1995, year).

He continued to work, still holding significant posts in the area. In 1996, he met his future wife, in 1997 he got married. Family life was problematic due to conflicts with the wife’s parents and the spouse’s unwillingness to open his side. Since 1997, he has been quite successfully engaged in his own business, leasing land.

In July 2002 (30 years), against the background of a stressful situation, the fear of "breaking loose" sharply increased. Having hardly reached the destination by car, when he saw his brother, he asked him to “hold his hands”, believing that “he was about to commit the irreparable”. I felt a pronounced heartbeat, lack of air; everything around seemed unreal, "like a dream." For help, they turned to the district hospital, where an injection of relanium was performed, which improved the condition. In the future, he constantly took phenazepam.

In November 2002, they first contacted a psychiatrist. Prescribed medications (nootropics) not only did not lead to improvement, but contributed to the increase in obsession. The range of prescribed drugs expanded: carbamazepine, clonazepam, phenazepam, eglonil, haloperidol, atarax, piracetam, amitriptyline (from 20 mg / day to 60), diazepam, nicergoline. He took medications irregularly, without proper medical supervision.

In the spring of 2009, for no apparent external reason, panic attacks became more frequent, which led to an appeal to our Center.

Mental status. Consciousness is clear, correctly oriented in all forms. He comes to the conversation willingly, always well in advance, obviously weighed down by expectation. He tries to take free time, asks the doctor to speed up the start of the reception, explaining that “with an emergency, the anxiety increases." During the conversation, keeps free. Facial expressions and pantomimics live, correspond to the topics discussed. The voice is emotional, well modulated. Speech at a slightly accelerated pace without noticeable structural impairment. He monitors whether the doctor records what he says, fearing that part of the information “will be forgotten and unaccounted for.” Interested in examination and treatment, emphasizes details important to him, fixed on them. Smiling, joking easily, can be ironic over himself. When discussing topics of interest to him, he relaxes, looks satisfied, often smiles; after a pause or spontaneously clearly darkens, it looks somewhat detached, explaining by the fact that “the anxiety intensified again and unpleasant thoughts arose”.

Complaints of panic attacks, accompanied by fear of "break", i.e. be unable to resist the urge to hit yourself with a finger or other sharp object in the eye. During the attack he feels that "the world around is changing, becoming unreal." The heart "seems to be jumping out of the chest", trying to breathe as deep as possible, "but there is still not enough air." The attack ends with excessive urination.

There is no delirium and no hallucinations. The criticism is close to full: it agrees with the presence of a mental disorder that arose on the basis of its anxious-suspicious nature.

The results of a psychological study 12.5.09.

The examination revealed: pronounced mood swings; increased personal and reactive anxiety; decreased performance due to asthenization of arbitrary processes (attention, random access memory); inertia of thought processes; specific experiences and fears of the psychasthenic circle, characteristic of a neurotic symptom complex in the stage of decompensation, the level of disorders in the stage of decompensation.

The results of additional studies.

- EEG 6.5.09. In the background recording, mainly functional changes are recorded, possibly due to emotional fluctuations (high level of anxiety).

- KTGM 8.5.09. No evidence of organic pathology.

- Daily urine for catecholamines 10.5.09. Dopamine 2097 nmol / day (norm 665-1357).

12.5.09 a consultation was held consisting of: prof., MD Bukhanovsky A.O., doctor of medical science Soldatkin V.A .. Diagnosed with panic disorder.

The treatment was carried out: at the same time, clonazepam was prescribed at a dose of 2 mg per day and ethifoxin (stresam) 1 capsule 3 times a day. The duration of clonazepam therapy was 2 weeks, then the dose began to decrease (by 25% per week), while the dose of etifoxin (stresam) remained unchanged. On the first day of a dose reduction of clonazepam, a panic attack developed. The dose of clonazepam has been restored to the previous level, an antipsychotic has been introduced into the regimen (quetiapine, 100 mg per day). 2 weeks after stabilization of the condition, the attempt to cancel clonazepam was repeated, the cancellation was uneventful. After the cancellation of clonazepam, therapy continued with the use of etifoxin (stresam) and antipsychotic as the main drug. The gradual withdrawal of drugs began 3 months after the last panic attack, carried out successfully.

Follow-up: 2 years. The condition remains good.

The proposed method treated 34 patients suffering from PR.

Follow-up monitoring of patients who received care was performed in the period from 6 months to 2 years. Persistent remission was achieved in 18 (52.9%) cases, a noticeable improvement in 14 (41.2%) patients. The method was ineffective in 2 (5.9%) patients.

The technical and economic effectiveness of the "Method of pharmacotherapy of panic disorder" lies in the fact that the use of the method can significantly increase the effectiveness and safety of PR therapy.

Claims (1)

A method of treating panic disorder, including the use of psychopharmacotherapy, characterized in that when the diagnosis of Panic Disorder is established, the patient is simultaneously prescribed clonazepam at a dose of 2 mg per day and etifoxin 1 capsule 3 times a day, as soon as possible, a study of daily dopamine excretion is performed; the duration of clonazepam therapy is 2 weeks, then the dose begins to decrease by 25% per week, while the dose of Etifoxin remains unchanged; with positive dynamics, a dose reduction results in the abolition of clonazepam, if an exacerbation occurs, the previous dose of clonazepam is prescribed and, in the case of a paraclinically detected increase in daily excretion of dopamine, an antipsychotic; 2 weeks after stabilization of the condition, the attempt to cancel clonazepam is repeated; after cancellation of clonazepam, therapy is continued with the use of etifoxin and, in the case of an identified increase in daily excretion of dopamine, an antipsychotic; gradual drug withdrawal begins 3 months after the last panic attack.