RU2696782C1 - Method of relieving resistant depressive syndromes of psychosomatic circle - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to psychiatry, and concerns the management of resistant depressive psychosomatic syndromes. That is ensured by parenteral introduction of tricyclic antidepressants combined with neuroleptics. Combination is obtained by mixing in 200 ml of physiologic saline successively 2.0–6.0 ml of 1.25 % clomipramine (anaphranil) and 1.0–2.0 ml of 0.2 % trifluoperazine (triftazine) solution. Administration is performed intravenously for 1.5–2 hours with control of arterial pressure and pulse every 30 minutes, followed by rest for 30–40 minutes, course of treating 12–14 infusions. That is followed by a strategic maintenance pathogenetic therapy for 6 months with the oral administration of clomipramine (anaphranil) in dose of 50–75 mg in a combination with trifluoperazine (triftazine) in dose of 2.5–5 mg.

EFFECT: introduction of such combination of medicinal preparations in the specified mode provides fast overcoming of therapeutic resistance in the given group of patients with minimum by-effects.

1 cl, 3 ex

Description

The invention relates to medicine, namely to psychiatry.

There are methods for stopping neurotic level depressive syndromes that are resistant to therapy with tricyclic antidepressants: the initial dose of amitriptyline or melipramine should be at least 75 mg, the dose build-up rate should be 25-50 mg per day, the average therapeutic dose of amitriptyline should be 250-300 mg per day, oral administration of amitriptyline or melipramine is recommended (G.Ya. Avrutsky, “Treatment of the mentally ill”, 1981, p. 343). Combinations of amitriptyline with antipsychotics are also acceptable ((G.Ya. Avrutsky, “Treatment of the Mentally Ill,” 1981, p. 71).

However, in the treatment method G.Ya. Avrutsky is firstly used, oral administration of antidepressants, which helps prolong the course of the depressive phase, leads to prolongation of therapeutic resistance, and secondly, large doses are used, which leads to severe side effects, reducing the quality of life of patients.

There is a method for the treatment of resistant depression proposed by Yu.L. Nuller (Yu.L. Nuller, “Affective Psychoses”, 1988, pp. 103-104). For moderate and severe depression, treatment is carried out starting with iv drip of large doses of tricyclic antidepressants (6-8 ml), increasing the dose over 3-4 days to 16 ml-20 ml. In some cases, the daily dose of tricyclic antidepressants can be brought up to 32-36 ml. Treatment of resistant depression is recommended by changing the tricyclic antidepressant or by the addition of electroconvulsive therapy (Yu.L. Nuller, “Affective Psychoses”, 1988, pp. 122-123).

However, in the treatment method of Yu.L. Nuller also uses large, subtoxic doses of tricyclic antidepressants, which leads to the occurrence of a large number of side effects in patients, reducing the patient’s “quality of life”. In addition, the treatment method of Yu.L. Nuller is designed only for an inpatient patient, and cannot be used for day care, which limits the possibility of using psychopharmacotherapy, increasing the risk of developing "hospitalism" of patients.

The closest in technical essence is a method of treatment of depressive syndromes of the psychosomatic circle that are resistant to therapy. (A.B. Smulevich, Depression in Somatic and Mental Illness, 2003, p. 284-286). For the relief of resistant depressive syndromes, it is recommended that intensive psychopharmacotherapy is carried out using high doses of thymoanaleptics (tricyclic antidepressants administered parenterally, as well as serotonergic and double-acting drugs), prescribed in combination with psychopharmacological drugs of other classes (atypical antipsychotics, traditional antipsychotropin-producing) . The duration of intensive care should be at least 3 months and the continued use of maintenance therapy over the next 2 years.

However, in the treatment method of A.B. Smulevich is recommended to use only intensive administration of antidepressants, and antipsychotics are administered orally and we are talking about long-term intensive care (about 3 months). Such long-term therapy requires the patient to be in stationary conditions, which also enhances “hospitalism”, iatrogenic effect and does not accelerate the patient’s exit from prolonged, therapy-resistant depression.

The task of quickly stopping resistant depressive syndromes of the psychosomatic circle, reducing side effects.

The problem is achieved in / in the dropwise administration of a complex pharmacological composition (SFC) of a tricyclic antidepressant and antipsychotic obtained by mixing in 200 ml of physiological solution successively 2.0-6.0 ml of 1.25% clomipramine (anafranil) and 1.0-2 , 0 ml of a 0.2% solution of trifluoperazin (triftazine), by infusion lasting 1.5-2 hours, with blood pressure and pulse monitoring every 30 minutes, followed by rest for 30-40 minutes, a course of treatment of 12-14 infusions, followed by stratum for 6 months with the supportive pathogenetic therapy, with oral administration of clomipramine (anafranil) at a dose of 50-75 mg in combination with trifluoperasin (triftazine) at a dose of 2.5-5 mg.

The antidepressant clomipramine is very similar in structure to the other antidepressant amitriptyline and belongs to the group of tricyclic antidepressants. However, unlike amitriptyline, it contains two nitrogen atoms, one of which is part of the central seven-membered heterocycle and is associated with two closed aromatic systems.

For this reason, its electron pair does not exhibit basic properties and clomipramine is in the form of hydrochloride. Due to the similarity of the structures of amitriptyline and clomipramine, it can be assumed that there is no interaction between clomipramine and trifluoperazin. From which it follows that these drugs can be combined and administered as part of SFC on the basis of physiological solution into the patient's body during therapy. Another component that is part of the SFC trifluoperazin (triftazine), a piperidine derivative of phenothiazine, also has a tricyclic structure containing two conjugated benzene rings, one of which has the trifluoromethyl radical.

The electron pair of the nitrogen atom entering the central heterocycle is conjugated with two aromatic sextets of benzene moieties; therefore, the basic properties of trifluopyrazine nitrogen are significantly weakened. This nitrogen is bonded to a phenothiazine radical containing two nitrogen atoms bonded to a carbon atom. It is these atoms that cause the interaction with hydrogen chloride, stay in the form of dichloridophenothiazine, and also cause good solubility in water. Thus, both clomipramine (anafranil) and trifluopyrazine (triftazine), which is part of the SFC, have similarities in structure, are essentially tricyclic. The radicals they have attached to cyclic structures contain nitrogen atoms bonded to carbon atoms that react well with hydrogen chloride and convert the preparations to ionic form in solution. Thus, the similarity in the structures, as well as the presence of ionic nitrogen atoms, allows a synergistic effect while entering the central nervous system (CNS), reducing the adverse symptoms of exposure to each substance separately.

The method is as follows.

Treatment is carried out in a hospital or day hospital. The patient is given an intravenous drip infusion of SFC, which is created by mixing in 200 ml of physiological solution successively clomiroamine (anafranil) (1.25% solution of 2 ml) and trifluoperazine (triftazine) (0.2% solution of 1.0 ml). In case of resistant depressive syndromes of the psychosomatic circle, 2.0 ml of 1.25% solution of clomipramine (anafranil) and 1.0 ml of 0.2% solution of trifluoperazin (triftazine) per 200.0 ml of physiological saline are administered intravenously. Depending on the severity of the condition, after 2-3 days of therapy, the dose of clomipramine is increased to 4.0-6.0 ml, and the dose of triftazine can be increased to 2.0 ml. In total, 12-14 intravenous infusions are performed. The duration of intravenous infusion is 1.5-2 hours. Every 30 minutes, blood pressure and pulse are monitored. After infusions, rest is recommended for 30-40 minutes. For strategic supportive pathogenetic therapy, within 6 months, clomipramine (anafranil) is prescribed in a dose of 50-75 mg in combination with trifluoperasin (triftazine) in a dose of 2.5-5 mg

Examples:

1. Patient M. 39 years. Received treatment with complaints of severe anxiety (especially in the morning), sleep disturbances (pre-, intra-, post-somnic disorders), lack of appetite (she lost 14 kg in 6 months), disturbance of the monthly cycle in the form of delay, reduced mood, lack of strength, desire to do something, pains of an unclear nature in the head area, accompanied by a “tingling sensation, burning sensation”, not stopped by the administration of analgesics. The patient was repeatedly examined and treated by neurologists in various neurological hospitals with a diagnosis of tension headache. This condition in the patient lasts for 1.5 years and began after a long chronic psycho-traumatic situation related to her personal life. After resolving the trauma, the condition did not improve. For 1.5 years, neurologists and psychotherapists prescribed antidepressants twice: first, for about 4 months, they took selective serotonin reuptake inhibitors (SSRIs) at an average therapeutic dose, but without improvement, and then took a course of 2.0 ml intravenous drip. 1% solution of amitriptyline (No. 10) in the conditions of an outpatient clinic. But no improvement was noted. Based on complaints, medical history, psychopathological and pathopsychological examination, a diagnosis was made according to the International Classification of Diseases (ICD) - 10: recurrent depressive disorder, current episode of moderate degree with somatic symptoms. An intravenous drip of SFK was used, consisting of 2.0 ml of a 1.25% solution of anafranil and 1.0 ml of a 0.2% solution of triftazine in a course of 14 procedures. For 3-4 days, anxiety decreased, mood improved, anxiety completely stopped at the end of the course of treatment, vital functions normalized, mood improved, depressive experiences deactivated, the intensity and frequency of senesto-allergic sensations decreased, a positive attitude for future life appeared .. After the course, the patient was transferred to strategic supportive pathogenetic therapy with anafranil at a dose of 50 mg in combination with triftazine at a dose of 2.5 mg per day, course of 6 months.

2. Patient B. 47 years. He was admitted for treatment on the recommendation of a gastroenterologist. Upon receipt of a complaint of depression, apathy, “lack of strength, desire to do something”, decreased mood, sleep disturbances, appetite (lost 8 months for 14 kg), constant pain in the abdomen, nausea, sensations of “constant discomfort "In the intestines. The patient was observed for 8 months and was treated by a gastroenterologist with a diagnosis of irritable bowel syndrome. He was constantly taking medications according to the standards of treatment for this nosology by gastroenterologists, but without a significant improvement. For 4 months, he took eglonil in a dose (600 mg per day) on the recommendation of a psychiatrist — noted that in the first 2-3 weeks of taking eglonil, the condition improved slightly, but then again “became bad” - nausea intensified, “unpleasant burning sensations ”in the intestine, permanent abdominal pain. Based on complaints, anamnesis, psychopathological and pathopsychological examination, a diagnosis of ICD - 10 was made: recurrent depressive disorder, current episode of moderate degree with somatic symptoms. An intravenous drip of SFC was used, consisting of 4.0 ml of a 1.25% solution of anafranil and 2.0 ml of a 0.2% solution of triftazine, in a course of 14 procedures. Nausea decreased by 3-4 days, noted a decrease in pain with surprise, at the end of the course of treatment the pain completely stopped, vital functions normalized, mood improved, depressive experiences deactivated, the intensity and frequency of senestoalgic sensations decreased, and a positive attitude towards future life appeared. After the course, the patient was transferred to strategic supportive pathogenetic therapy with anafranil at a dose of 75 mg in combination with triftazine at a dose of 5 mg per day, course of 6 months.

3. Patient N., 23, was taken for treatment by an ambulance to the cardiology department with complaints of pain in the heart, increased blood pressure, fear of a heart attack, anxiety, poor sleep, low mood, lack of strength. According to the ambulance doctor - an ECG without pathological disorders, after the injection of diazepam (oil 10.0 mg), according to the ambulance doctor, the patient calmed down slightly, the pain in the heart area decreased. In the first 10 minutes of being in the hospital, the cardialgic sensations intensified again - the patient's father began to demand a call for cardiac resuscitation, repeated ECG. According to the anamnesis, the patient was constantly observed by cardiologists for 14 months with a diagnosis of vegetative-vascular dystonia, underwent numerous examinations by therapists and cardiologists who did not reveal pathological disorders. In the last 3 months, on the recommendation of a therapist, he takes phenazepam at a dose of 2-3 mg per day, which improves the condition for 1-2 hours. Based on complaints, medical history, psychopathological and pathopsychological examination, a diagnosis of ICD-10 was made: recurrent depressive disorder, current episode of moderate degree with somatic symptoms. An intravenous drip of SFK was used, consisting of 2.0 ml of a 1.25% solution of clomipramine (anafranil) and 1.0 ml of a 0.2% solution of trifluoperazine (triftazine), in a course of 14 procedures. For 3-4 days, the patient's anxiety decreased, cardialgia decreased, at the end of the course of treatment anxiety completely stopped, vital functions normalized, mood improved, depressive experiences deactivated, the intensity and frequency of senestoalgic sensations decreased. After the course of treatment, the patient was transferred to a strategic supportive pathogenetic therapy with anafranil at a dose of 50 mg in combination with triftazine at a dose of 2.5 mg per day, a course of 6 months.

Thus, the use of the proposed method for the relief of resistant depressive syndromes of the psychosomatic circle, contributes to the rapid relief of resistant depressive syndromes of the psychosomatic circle both in a hospital, tact and in a day hospital. The use of SFC in the form of a combination of clomipramine (anafranil) with strifluoperazin (triftazine) with iv drip, helps to accelerate the overcoming of therapeutic resistance to "minimize" side effects, to reduce the time of inpatient treatment, which reduces "hospitalism", "iatrogenic" effects, increases the "quality of life" of patients with the continued use of oral administration of small doses of anafranil and triftazine as a strategic supportive pathogenetic therapy.

Claims (1)

A method for stopping resistant depressive syndromes of the psychosomatic circle, including parenteral use of tricyclic antidepressants in combination with antipsychotics, characterized in that they use intravenous administration of a complex pharmacological composition of a tricyclic antidepressant and antipsychotic obtained by mixing in a volume of 200 ml of physiological solution 2.0 to 6.0 ml sequentially 1.25% clomipramine (anafranil) and 1.0-2.0 ml of a 0.2% solution of trifluoperazin (triftazine), by infusion lasting 1.5-2 hours and with blood pressure and pulse monitoring every 30 minutes, followed by rest for 30-40 minutes, a course of treatment of 12-14 infusions, and further strategic supportive pathogenetic therapy is carried out for 6 months with oral administration of clomipramine (anafranil) at a dose of 50- 75 mg in combination with trifluoperazin (triftazine) at a dose of 2.5-5 mg.