Paroxetine

Paroxetine is a drug from the antidepressant group. Known since the late 1980s. Currently widely used for depression of all types (atypical, seasonal, psychotic, postpartum, dysthymia, etc.), obsessive-compulsive neurosis, episodic paroxysmal anxiety (including those associated with fear of open space), social and generalized anxiety disorders, post-traumatic stress disorder, premenstrual dysphoric disorder, chronic headaches. The antidepressant effect of the drug is determined by its ability to selectively suppress the uptake of serotonin by neurons in the brain - the so-called. “hormone of good mood” or “hormone of happiness” (in terms of the severity of this property, paroxetine is a leader among all antidepressants known today). The drug is well absorbed from the gastrointestinal tract, partially undergoing a first-pass effect through the liver with the formation of pharmacologically inert metabolites. A stable concentration of the active substance in the blood is achieved after 4-14 days of regular pharmacotherapy. The half-life of the drug is 21 hours, which makes it possible to limit the drug to a single dose per day (and this, in turn, increases compliance, i.e., the patient’s adherence to treatment). The pharmacokinetic characteristics of paroxetine vary depending on the age of the patients. The rate of elimination in persons suffering from liver and kidney diseases is reduced.

The drug has a favorable safety profile and, provided the recommended dosage instructions are followed, rarely causes side effects. Paroxetine does not suppress psychomotor processes and does not enhance the inhibitory effect on psychomotor activity of ethanol-containing products. According to a study of behavioral reactions and an encephalogram, the drug exhibits a weak activating effect when slightly exceeding the recommended doses. There are no significant changes in blood pressure, heart rate and EEG. Paroxetine is contraindicated in case of individual intolerance to the components, unstable epilepsy, during pregnancy and breastfeeding, when taking monoamine oxidase inhibitors (and for two weeks after the end of their use). The drug is not used in pediatric practice. Daily dose – 1 tablet. The optimal time to take it is in the morning, during breakfast. Dose selection is carried out on an individual basis with the possibility of further adjustment after two to three weeks from the start of pharmacotherapy. The presence of food contents in the gastrointestinal tract and the use of medications that reduce gastric acidity do not affect the pharmacokinetic characteristics of paroxetine. During drug therapy, it is recommended to abstain from drinking alcohol. Despite the fact that the drug does not affect psychomotor and cognitive functions, during treatment you should be careful when engaging in activities that require increased attention and reaction speed, incl. driving a car.

Anxiety disorders and experience with paroxetine

Anxiety disorders are extremely common, with 13–25% of the population experiencing anxiety disorders in their lifetime. According to the DSM-IV (Diagnostic and Statistical Manual) classification, anxiety disorders include [10]:

panic disorder;
generalized anxiety disorder;
agoraphobia without panic disorder;
obsessive-compulsive disorder;
social phobia;
specific phobias;
post-traumatic stress disorder;
acute stress disorder.

Many people are familiar with the symptoms of anxiety. They can be divided into general (mental and vegetative) and specific, determining the type of anxiety disorder. Common mental symptoms include restlessness, irritability, anxious thoughts, motor agitation, flinching at sudden sounds, decreased concentration, increased fatigue, impatience, inability to relax, sleep disturbances, and nightmares. The anxious mood is perfectly conveyed in Edvard Munch’s painting “Anxiety” (Fig. 1).

As a rule, mental symptoms of anxiety are accompanied by vivid vegetative symptoms. Thus, the face of the woman depicted in the picture is pale, tense, and her lips are dry. She keeps her hands on her neck. Perhaps this is a feeling of shortness of breath, a coma in the throat and a feeling of chills. Other autonomic symptoms of anxiety include tachycardia, increased sweating with cold, clammy palms, hot flashes or chills, dyspeptic disorders (abdominal pain, flatulence, diarrhea), dizziness, increased urination, increased physiological tremor, and increased muscle tone.

Clinical forms of anxiety disorders

Generalized anxiety disorder (GAD) is one of the most common forms of anxiety, with 4–9.2% of the population experiencing it during their lifetime [20]. The DSM-IV criteria for GAD are the presence of anxiety and restlessness in combination with at least three of the following symptoms:

impatience or feeling on edge;
increased fatigue;
difficulty concentrating or feeling empty in the head;
irritability;
muscle tension;
sleep disorders.

The duration of the disease must be at least 6 months, the symptoms must cause significant distress or affect social, professional and other areas of activity.

Panic disorder is also extremely common: according to epidemiological studies, panic attacks are observed in 1.5–4% of the population [11], although 35.9–46% of the human population have experienced panic at least once in their lives [2]. Panic disorder affects 6% of people seeking primary care [2]. The main clinical manifestation of panic disorder is panic attacks - attacks of severe anxiety, accompanied by somatic and cognitive symptoms. The main diagnostic signs of panic attacks are paroxysmal occurrence, polysystemic vegetative symptoms, and the presence of emotional disorders, the severity of which can range from a feeling of “discomfort” to “panic” [2]. Agoraphobia is very similar to panic disorder and is defined as anxiety that occurs in response to situations in which the solution is difficult or difficult, or when help will not be available if a panic attack develops. If anxiety in panic disorder can be defined as anxiety in anticipation of a subsequent attack, then agoraphobia is characterized by the presence of provoking factors or situations - being alone outside the house, being in a crowd, on a bridge (as in a Munch painting), traveling on public transport, etc. Provoking situations are actively avoided by patients; getting into them is accompanied by significant distress.

Specific phobias are characterized by the connection of anxiety with certain situations (air travel, contact with animals, the sight of blood, etc.), also accompanied by an avoidance reaction. Finding yourself in a phobic situation provokes an anxious reaction, similar to a panic attack. Patients are critical of their experiences, however, phobias have a significant impact on various areas of the patients’ activities. An example of a specific phobia can be found in the famous artist Pablo Picasso. “For a long time he was deathly afraid of getting his hair cut. For months I wore my hair too long and was hesitant to go to the hairdresser. As soon as someone started talking about it, he fell into a real panic. As a rule, it ended with him asking his loved ones to shorten his hair or locking himself in a small room and trying in vain to cut off his hair himself” [3, 11].

Social phobia is characterized by the occurrence of anxiety in social situations - communication and self-presentation (public speaking or even being in public), fear of possible condemnation from others. As with other anxiety disorders, patients actively avoid social situations because the anxiety causes them significant distress. Thus, the Russian critic and publicist V. G. Belinsky writes: “One thing torments me terribly: my timidity and embarrassment do not weaken, but increase in monstrous progression. I can’t show myself in public: my face is flaring up, my voice is trembling, my arms and legs are shaking, I’m afraid of falling. Self-affirmation is carried out in forms that are in every possible way opposed to accepted norms of behavior. Hence the eccentricity, wildness, and absurdity” [7, 11].

Obsessive-compulsive disorder is characterized by the presence of intrusive thoughts (obsessions) that increase anxiety and ritual actions or thoughts aimed at suppressing this anxiety. There are two key characteristics of symptoms in obsessive-compulsive disorder: egodystonia (the patient is unable to ignore or suppress the symptoms, although he is fully aware of their absurdity) and the presence of significant distress for a significant time (more than an hour a day). The most common obsessions are fear of contamination (45%), pathological doubts (42%), somatic obsessions (36%), the need for symmetry (31%), aggressive impulse (28%), sexual impulse (26%) [14]. Among the compulsions, the most common are checking (60%), washing (50%), counting (36%), the need to ask or admit something (31%), the need for symmetry/neatness (28%), hoarding (18%). ). Distinctive features of obsessive-compulsive disorder from other forms of anxiety disorders are an earlier age of onset, equal representation among both sexes (other forms of anxiety are more common in women), and a fairly high resistance to serotonergic drugs.

Post-traumatic stress disorder has 17 core symptoms, grouped into three groups: re-experiencing the trauma (instructive thoughts, nightmares, emotional and somatic reactions in response to memories), avoidance of memories associated with the trauma (avoidance of thoughts, feelings, places, acquaintances, inability to remember details of a situation, decreased interest in entertainment, withdrawal from other people, lack of prospects for the future) and agitation (sleep disturbances, irritability, difficulty concentrating, hypervigilance and increased startle reflex).

Difficulties in diagnosing anxiety disorders

The main reasons for underdiagnosis of anxiety disorders are the presence of subsyndromal forms of anxiety, as well as a wide range of comorbid disorders - depression, chronic pain syndromes, and other forms of anxiety disorders.

Diagnostic criteria for anxiety disorders are widely presented in the literature and are known to practicing physicians. However, in their daily practice, neurologists and internists much more often see not developed, but subsyndromal forms of anxiety disorders, when in the clinical picture of the disease it is not the mental, but the somatic or neurological components of anxiety that come to the fore. Thus, in the case of GAD, the DSM-IV diagnostic criteria have a significant drawback - they are mainly focused on the presence of mental symptoms, which can lead to underdiagnosis of the anxiety disorder. In the ICD-10 criteria, to make a diagnosis of GAD, the presence of 4 symptoms out of 22, divided into five groups - vegetative, respiratory or gastrointestinal symptoms, symptoms affecting mental activity, general symptoms and nonspecific symptoms, is required, but internists and doctors It is not always convenient for other specialties to use ICD-10 criteria. Starcevic V. et al. identified the most significant symptoms of GAD from the DSM-IV and ICD-10 classifications. The criteria proposed by the authors are much more convenient to use in everyday practice (

.) [18].

Recent epidemiological studies have shown a high prevalence of subsyndromal panic disorder that does not meet diagnostic criteria. In these cases, panic attacks, although rare, anxiety also significantly affects the lives of such patients [15]. Certain diagnostic difficulties can be caused by atypical panic attacks when clinical phenomena not covered by DSM-IV criteria are observed during an attack—diffuse or local pain syndromes, senestopathies, muscle tension, obsessions and compulsions, etc. [2]. There are 10 atypical, conversion symptoms of panic attacks: (1) feeling of a lump in the throat, (2) feeling of weakness in an arm or leg, (3) visual or hearing impairment, (4) gait disturbance, (5) speech or voice disturbance, ( 6) loss of consciousness, (7) a feeling that the body is arching, (8) cramps in the arms and legs, (9) nausea, vomiting, (10) abdominal discomfort [2].

When making a diagnosis of agoraphobia, it is necessary to remember that in cases where the patient has only one or two anxiety-provoking situations, it is necessary to think about specific phobias, and if the anxiety is associated only with social triggers, then about social phobia.

Another feature of panic disorder and agoraphobia is the presence of permanent autonomic disorders, which can occur predominantly in one system or be multisystem in nature [2]. These disorders can be the reason for contacting specialists of various profiles. Thus, patients can come to see a cardiologist with cardialgia, cardiosenestopathies, arterial hypo- and hypertension, syncope and lipothymic conditions, a feeling of lack of air, a feeling of suffocation, and Raynaud's syndrome. Gastroenterologists may encounter in their practice patients who persistently complain of dyspeptic symptoms, dry mouth, nausea, abdominalgia, constipation or diarrhea. Such patients should always request that their anxiety disorder be excluded.

Like other anxiety disorders, obsessive-compulsive disorder is underdiagnosed. Typically, patients with obsessive-compulsive disorder are embarrassed to talk about mental symptoms, even when asked about them directly. The following 5 questions can help a practitioner diagnose this type of anxiety disorder [19]:

Do you wash or clean things a lot?
Do you check something over and over again?
Do you have thoughts that bother you that you would like to get rid of, but you can’t?
Do your daily activities take up a lot of your time?
Is your attention focused on any order or symmetry?

Depression is an integral accompaniment of anxiety. Anxiety disorders occur in 57% of patients with depression [15]. The combination of anxiety and depression significantly aggravates the course of the disease. This is manifested by more severe symptoms, a tendency to chronicity, mental dysfunction, refusal to work, greater seeking of medical help, a greater risk of suicide and resistance to therapy.

Paroxetine in the treatment of anxiety disorders

Drugs of various pharmacological groups are used to treat anxiety disorders. However, antidepressants are currently considered the drugs of choice. Widely used until recently, anxiolytics, most of which are benzodiazepines, are not used as a basic drug, primarily due to frequent complications: sedation, behavioral toxicity, paradoxical reactions, tolerance, addiction, dependence, withdrawal and rebound syndrome, as well as the presence of drugs interactions. Among antidepressants, preference should be given to selective serotonin reuptake inhibitors (SSRIs) as they are effective and the most well tolerated drugs. Among the SSRIs, paroxetine is the most studied drug in the treatment of anxiety disorders.

For GAD, paroxetine has shown its effectiveness both in comparison with placebo and tricyclic antidepressants and benzodiazepines [17]. Thus, among patients receiving paroxetine, remission was achieved in 72%, while among patients receiving placebo, only 34% (p < 0.001). Already at 4 weeks of use, paroxetine significantly improved the level of anxiety on the HAM-A scale by 15.6 points compared to benzodiazepine, which improved the anxiety score by only 11.8 points (p < 0.01). The dose of paroxetine effective for the treatment of GAD is 20–40 mg/day (10–50 mg/day) [17].

Paroxetine is the most studied drug in the treatment of panic disorder and agoraphobia. In a large placebo-controlled study, paroxetine was effective compared with placebo, characterized by the occurrence of an attack-free period, at a dose of 40 mg/day (p < 0.02). Thus, when taking paroxetine, an attack-free period occurred in 86% of patients, and when taking placebo - in 50%. Paroxetine also had a significantly lower relapse rate (5%) compared to placebo (30%), p = 0.002 [16].

Studies have also been conducted on the effectiveness of paroxetine for social phobia and post-traumatic stress disorder. Among patients with social phobia, 55% of patients taking paroxetine and 24% of patients taking placebo were responders. In a study of the effectiveness of paroxetine for post-traumatic stress disorder, the differences with placebo were less significant due to the high placebo effect. In the paroxetine group, 60% of patients were responders, in the placebo group - 49% [19].

Obsessive-compulsive disorder is the most resistant to treatment among anxiety disorders. However, the effectiveness of paroxetine has also been proven in this form of anxiety, although in higher doses (40–60 mg/day). The paroxetine group showed a significant improvement on the Y-BOCS scale compared to placebo. The relapse rate was also significantly lower in the paroxetine group (38%) compared with the placebo group (59%), p < 0.033 [13].

Paroxetine has a favorable safety profile. The main side effects when taking it are headache, nausea and other gastrointestinal disorders, sleep disorders and sexual dysfunction. Side effects are not pronounced and regress on their own during the first weeks of taking the drug. The cardiac safety of paroxetine appears to be proven [12].

There is extensive experience in the use of Rexetine (paroxetine), including in domestic clinical practice. The clinical effects of Rexetine have been most studied in the treatment of anxiety disorders encountered in the practice of a neurologist and internist, although it can also be used in psychiatric clinics. Thus, in a study of the effectiveness of Rexetine at a dose of 20–60 mg/day in the treatment of anxiety and depressive disorders in patients who consulted a psychiatrist, the proportion of responders was 50% [1]. When taking Rexetine in patients with anxiety and depressive disorders against the background of dyscirculatory encephalopathy, remission was observed in 91% of patients [8].

In a neurological hospital, Rexetine was effective not only for panic disorder, but also for other diseases accompanied by anxiety - somatized dysthymia, “masked” depression, migraine, tension headache, and other chronic pain syndromes [4].

In the work of Less Yu. E. et al. [6] studied the effectiveness of Rexetine at a dose of 20 mg/day for GAD, taking into account comorbid anxiety and affective conditions (panic disorder, agoraphobia, obsessive-compulsive disorder, depression). The patients were divided into three groups. The first group consisted of patients with isolated GAD, the second group included patients with GAD accompanied by erased comorbid disorders at the subsyndromal level. The third research group included individuals with extensive, clinically significant comorbid disorders. The study confirmed the high effectiveness of Rexetine for GAD. In 35.9% of patients, a remission level was achieved by the end of the course of therapy, 17.9% were classified as responders, 28.3% as partial responders, and only 17.9% as non-responders. The dynamics of anxiety on the Hamilton scale, assessed in this study, are presented in

According to the dynamics of the total HAM-A score, a significant decrease in anxiety was noted at all time points (7, 14, 21, 28, 35 and 42 days from the start of taking Rexetine). The rate of reduction in symptoms, which was the same in all groups during the first two weeks of therapy, further slowed down in the group of patients with severe comorbid disorders, while in the groups of patients without comorbid disorders and with subclinical comorbid disorders, the therapeutic effect steadily increased, reaching a maximum level by the end of the study. By the time the course of therapy was completed, the regression of anxiety symptoms in the groups of patients without comorbid disorders and with subclinical comorbid disorders was significantly greater than in the group of patients with severe comorbid disorders [6]. Thus, this study confirms the information about the high effectiveness of Rexetine in the treatment of GAD. The anti-anxiety effect of the drug begins to manifest itself from the first days of therapy and gradually increases, reaching a maximum after a month of treatment. A dose of 20 mg appears to be adequate in most cases, but in cases of GAD complicated by comorbid emotional disorders, the dose of Rexetine should apparently be increased [6].

Rexetine has proven to be a highly effective drug for the treatment of specific phobias. With this form of anxiety disorder, a fairly rapid effect of Rexetine was noted. Already in the first week, there is a decrease in the feeling of internal tension, regression of vegetative symptoms (sweating, the intensity of the feeling of “incompleteness” of inspiration has decreased), and sleep improves. The most pronounced reduction in the intensity of anxious experiences and improvement in the well-being of patients was observed during the first 4 weeks of Rexetine therapy. Normalization of well-being to the initial, pre-painful state was observed starting from 3–4 weeks of treatment [9].

There is experience in using Rexetine in patients with somatic diseases and concomitant anxiety and depressive disorders. Thus, Rexetine can be used with antihypertensive, vascular, cardiological, antidiabetic and other drugs that are often necessary for patients for health reasons. It has been established that it does not cause addiction or dependence [5].

Our experience in using Rexetine in patients with anxiety and anxiety-depressive disorders showed that among 20 observed patients, 12 people (> 50%) noted complete remission after 6 months of therapy. In approximately 2/3 of cases (13 patients), comorbidity with depressive spectrum disorders was noted. The most common manifestations were: sad mood, depression, sleep disturbances, pain (in the neck and lower back), slowness of movements and speech. During therapy, a gradual reduction of these manifestations was observed. In the dynamics of anxiety symptoms, such manifestations as anxiety, fatigue, irritability, and muscle tension underwent the greatest regression. It should also be noted the effect of therapy on the presentation of autonomic manifestations of anxiety: tachycardia, hot and cold flashes, cold extremities. In general, according to patient reports, 14 of them (70%) rated the results of treatment as “good” or “excellent”. It should be noted that at the time of therapy, 4 patients were taking pharmacological agents prescribed by internists for concomitant diseases (beta-blockers, antihistamines, vasoactive drugs). In no case were there any signs of drug interactions. In addition, during therapy, one patient noted a decrease in episodes of existing tension-type headaches, in two cases a reduction in insomnia was observed, 4 patients noted a decrease in the intensity of accompanying pain manifestations (pain in the cervical region and lower back) and a decrease in the amount of analgesics consumed while taking Rexetine.

Thus, the proven effectiveness, high safety of Rexetine and extensive experience in its use in the treatment of anxiety disorders allow this drug to be actively used in everyday practice by doctors of various specialties.

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G. R. Tabeeva Yu. E. Azimova

MMA im. I. M. Sechenova, Moscow

Table.

Rice. 2.

Paroxetine, 30 pcs., 20 mg, film-coated tablets

Paroxetine is an antidepressant. It is a selective inhibitor of serotonin (5-hydroxytryptamine, 5-HT) reuptake by brain neurons, which determines its antidepressant effect and effectiveness in the treatment of obsessive-compulsive (OCD) and panic disorder.

Paroxetine has low affinity for m-cholinergic receptors (has a weak anticholinergic effect), α1-, α2- and β-adrenergic receptors, as well as dopamine (D2), 5HT1-like, 5HT2-like and histamine H1 receptors. Paroxetine does not disrupt psychomotor functions and does not potentiate the inhibitory effect of ethanol on them.

Behavioral and EEG studies show that paroxetine exhibits weak activating properties when administered at doses above those required to inhibit serotonin uptake. Does not cause significant changes in blood pressure, heart rate and EEG levels.

Pharmacokinetics

Suction

After oral administration, paroxetine is well absorbed from the gastrointestinal tract and undergoes first-pass metabolism through the liver.

Distribution

Css is achieved 7-14 days after the start of therapy. With increasing dose and/or duration of treatment, a nonlinear dependence of the pharmacokinetic parameters on the dose is observed.

Paroxetine is extensively distributed in tissues, only 1% of it is present in plasma.

95% protein bound.

Metabolism

Metabolized in the liver to form inactive metabolites. It is an inhibitor of the CYP2D6 isoenzyme.

The main metabolites of paroxetine are polar and conjugated oxidation and methylation products that are quickly eliminated from the body, have weak pharmacological activity and do not affect its therapeutic effect. When paroxetine is metabolized, the selective uptake of serotonin by neurons due to its action is not impaired.

Removal

About 64% of paroxetine is excreted in the urine (2% unchanged, 64% as metabolites); approximately 36% is excreted in bile through the intestines, mainly in the form of metabolites, less than 1% - unchanged.

The elimination of paroxetine metabolites is biphasic, initially as a result of first-pass metabolism through the liver, and then it is controlled by systemic elimination. T1/2 of paroxetine varies, but averages 24 hours.

Pharmacokinetics in special clinical situations

The concentration of paroxetine in the blood plasma increases with impaired liver and kidney function, as well as in the elderly.

Currently, antidepressants are used for pharmacotherapy of generalized anxiety disorder (GAD) [12], which allow achieving remission in 40-50% of patients. In a number of studies [1, 7, 13, 14, 19], preference when choosing antidepressants is given to selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Antidepressants have been proven to be effective against both ideational and somatic anxiety [2, 5, 6, 16-18]. It has been revealed that they have a stronger effect on ideation anxiety compared to tranquilizers [11, 15].

Almost all known SSRIs are currently used for GAD [8]. But a special profile of receptor interaction sets paroxetine apart from a number of serotonergic drugs [3]. Its effectiveness in GAD has been proven in a number of placebo-controlled studies [18, 19]. At the same time, the superiority of paroxetine over benzodiazepine tranquilizers in reducing the symptoms of ideation anxiety was established. However, a number of important aspects of the use of paroxetine in GAD remain poorly understood, especially given its clinical heterogeneity. So, Yu.E. Less [4] identified 4 clinical types of this disorder: affective, somatized, phobic and tonic. In patients with the affective type of GAD, the foreground in the clinical picture is the actual affect of anxiety (the so-called free-floating anxiety). With the somatized type of GAD, anxious experiences are accompanied by pronounced autonomic hyperactivity. The phobic type of GAD is characterized by a “struggle” with pronounced anxiety, which brings it closer to the phenomenon of obsession. With the tonic type, muscle tension, a feeling of stiffness, and the inability to relax with a minimum of autonomic disorders are especially pronounced. The clinical heterogeneity of GAD is also confirmed by the fact that in no more than half of the patients the condition is exhausted by the phenomena of generalized anxiety throughout the entire disease. In other cases, at one or another stage of the disease, other comorbid disorders may appear, primarily of the affective and anxiety spectrum (panic disorder, obsessive-phobic disorders, agoraphobia, simple phobia, depression, dysthymia). It remains unclear how the type of GAD and the listed comorbid disorders affect the effectiveness of treatment with paroxetine.

Currently, a drug from the paroxetine group has appeared on the domestic market under the trade name “adepress”. This drug is therapeutically equivalent to the original paroxetine and is available in the form of tablets containing 20 mg of the active substance.

The purpose of the study was to study the effectiveness of Adepress in various clinical variants of GAD, taking into account comorbid conditions.

Material and methods

The work was carried out in the Department of New Means and Methods of Therapy, Department of Borderline Psychiatry, State Scientific Center for Social and Forensic Psychiatry named after. V.P. Serbsky on the basis of the clinical department of the Moscow City Clinical Psychiatric Hospital No. 12.

The study was an open naturalistic study.

The criteria for inclusion of patients in the study were as follows: diagnosis according to ICD-10 - F41.1 - generalized anxiety disorder; the presence of GAD as the main disorder, including comorbid symptoms of the anxiety-phobic circle (agoraphobia, panic disorder, social phobia, obsessive-compulsive disorder); the number of points on the Hamilton Anxiety Scale (HAM-A) is at least 20 at the time of inclusion in the study; patient age ranges from 18 to 60 years; availability of informed consent to participate in the study.

Exclusion criteria were: schizophrenia, organic disease of the central nervous system, drug addiction, alcoholism; the number of points on the HAM-D scale is more than 15 at the time of inclusion in the study; pregnancy or lactation; clinically significant somatic diseases or laboratory abnormalities.

The study included 49 hospitalized and outpatient patients (13 men and 36 women).

The duration of the study was 42 days. The initial dose of Adepress was 10 mg/day, followed by a flexible dosing regimen in the range of 10-60 mg/day. Adepress was used as monotherapy. In case of severe anxiety, as well as insomnia, the use of small doses of benzodiazepine tranquilizers (alprozolam, lorazepam, phenazepam) was allowed in the first days of treatment.

The patients' condition was assessed using the Hamilton Anxiety Scale (HAM-A) before starting therapy and then over time - weekly. Reduction of symptoms to 7 points or less was assessed as the level of remission; 50% reduction in the sum of points - as a pronounced improvement (responders); reduction by 25-49% - as a slight improvement (partial responders); reduction of symptoms less than 25% - as no effect (non-responders).

Tolerability of the study drugs was assessed using the side effects scale (UKU).

The routine examination also included the somatic condition of the patients (body weight, blood pressure, heart rate, ECG, general and biochemical blood tests, general urinalysis).

Patients were examined before treatment (day 0) and then on days 7, 14, 21, 28, 35 and 42 of therapy.

4 patients dropped out during the 1st week of therapy. In 2 cases, the reason for exclusion from the study was the use of prohibited drugs, in one case it was a violation of the dosage regimen, and in another case it was withdrawal of consent. A common reason for discontinuation from the study was increased anxiety, with insomnia in one case.

Thus, 45 patients completed the study: 12 (26.7%) men and 33 (73.3%) women, whose average age was 36.2 ± 8.2 years. Of these, 31 (68.9%) people worked or studied, 14 (31.1%) did not work; 29 (64.4%) were married, 16 (37.6%) were single or divorced.

In accordance with the clinical types of GAD identified in previous studies, patients were distributed as follows: somatized type - 16 patients, affective type - 8, phobic - 9, tonic type - 11.

As follows from numerous publications [9, 10, 17, 18], the study of the anti-anxiety effect of antidepressants is carried out with an analysis of their impact on the cognitive (mental) and somatic (vegetative) components of the anxiety state. Since the study sample included patients with a predominance of somatic anxiety (21 patients) and a predominance of cognitive anxiety (24), the sample was divided into 2 corresponding groups. The average HAM-A score in group 1 (with a predominance of somatic anxiety) was 27.4 points, in group 2 (with a predominance of cognitive anxiety) - 28.3 ( p

>0.05), which indicated their comparability.

There were 19 (42.2%) cases of isolated GAD in the studied sample, while 26 (57.8%) cases of GAD occurring with comorbid mental disorders. It turned out that in group 1 (somatic anxiety), isolated GAD was more common (73.7%), and in group 2 (cognitive anxiety), comorbid GAD was more common (61.5%). Of the comorbid disorders in group 1, only panic attacks occurred - 10 (41.7%) cases. In group 2, the spectrum of comorbid disorders included dysthymia - 7 (33.3%) cases, obsessions - 8 (38.1%), panic attacks - 1 (4.8%).

Statistical processing of the results was carried out using the Student's test, qualitative indicators - using the χ2 method, comparative analysis of the dynamics of quantitative indicators - using the one-way analysis of variance method, comparative analysis of ordinal data - using the Mann-Whitney test.

The characteristics of mental disorders, including comorbid ones, in the study sample are presented in Table. 1.

Results and discussion

Positive dynamics in most cases were noted by the end of the 1st week of therapy; after 2 weeks of treatment, significant differences from the initial level were recorded in both groups (Fig. 1).

Figure 1. HAM-A indicators during Adepress therapy in groups 1 and 2 of patients. Differences compared to background p < 0.05;
* — significant differences between the two groups, established in χ2 (p<0.05). Further, the HAM-A score in both groups continued to decrease, reaching minimum values by the end of the study. At the same time, more pronounced dynamics were noted in group 1, and from the 3rd week, intergroup differences became significant ( p
<0.05).

The overall results of the effectiveness of therapy are given in table. 2.

The remission rate in both groups was approximately the same (29.2 and 28.6%), while the number of responders and non-responders differed significantly. In the 1st group of patients with somatic anxiety, by the end of the study there were approximately 2 times more responders (50% versus 28.6%), and in the group of patients with cognitive anxiety there were non-responders (42.8% versus 20.1%). Most cases of a positive reaction to Adepress therapy in group 1 occurred earlier than in group 2. As can be seen in Fig. 2, most of the responders were detected after 3 weeks of therapy, and after 4 weeks almost all remissions were formed.

Figure 2. Distribution of patients (%) in different groups according to therapeutic response over time.
The abscissa axis is weeks. In the cognitive anxiety group, the majority of respondents were also noted after 3 weeks of treatment, but a deeper reduction of symptoms, reaching the level of remission, in most cases occurred only by the end of the 6-week treatment period. It should also be noted that the best results in the group of patients with a predominance of somatic anxiety were achieved using a relatively lower dose of Adepress. The average dose at the end of the study in group 1 was 14.4 mg/day, in group 2 - 32.8 mg/day ( p
<0.05).

A comparative analysis of the therapeutic response in patients with isolated and comorbid GAD revealed the following results. In group 1, with isolated GAD, 42.8% of patients had remission, 50% were responders, and only 7.1% of patients were non-responders. Different ratios were found in this group for comorbid GAD: remissions - 10%, responders - 50%, non-responders - 40% of observations. In the group of cognitive anxiety, with isolated GAD, remissions were 80%, non-responders - 20%, with comorbid GAD, remissions were noted in 12.5% of patients, responders - 37.5%, half of the patients with comorbid GAD in this group turned out to be responders. Thus, the presence of comorbid symptoms adversely affected the results of therapy in both groups of patients.

When analyzing the results of therapy depending on the clinical type of GAD, the following differences were revealed (Table 3).

From the table Table 3 shows that the highest rates of effectiveness of Adepress were achieved in the affective type of GAD, where clinical improvement was recorded in all observations (remission - 37.5%, responders - 62.5%). In second place was the phobic type of GAD (36.4%), however, this type had the fewest responders (18.2%) and the highest frequency of no effect (45.4%). In the somatized type of GAD, 25% of remissions were observed, which, together with 43.7% of responders, totaled more than ⅔ of patients of this type with a positive response to Adepress therapy; non-responders accounted for 31.2% of cases. With the tonic type of GAD, 20% of remissions, 40% of responders and the same number of non-responders were recorded.

As for the tolerability of Adepress, during the study, certain side effects were identified in 27 patients; in 18 patients they were of a combined nature. All adverse events could be divided into 2 groups. Group 1 included so-called mental adverse events, manifested by increased anxiety and agitation (7 observations). They were recorded in the 1st week of therapy and appeared to be associated with the “hyperstimulation” phenomena described during therapy with serotonergic antidepressants. These phenomena, although pronounced, were quite short-term in nature and, as a rule, were stopped by the prescription of small doses of tranquilizers. The 2nd group of adverse events included somatic side effects from the gastrointestinal tract, represented by nausea and diarrhea (5 observations). These phenomena occurred in the first half of the study (until the 28th day), were subjectively moderately painful, but did not require drug correction and resolved within a few days on their own. Drowsiness during Adepress therapy was observed in 12 cases, occurring at the initial stage of therapy (1-2 weeks). The severity of daytime sleepiness was insignificant, and taking into account the characteristics of the mental state of the patients included in the study, these adverse events were perceived as partly positive, allowing them to reduce “internal tension.” Moderate headache (6 observations) occurred in the first days of therapy, hyperhidrosis (5) on days 14-21, sexual dysfunction (6) on weeks 4-6 of therapy. These side effects, described in detail in the literature, are associated with stimulation of serotonin receptors in the central and peripheral nervous system, which is characteristic of all serotonergic drugs, including Adepress.

It should also be noted that adverse events occurred more often in patients with the somatized type of GAD, which included all 4 patients who dropped out of the study, as well as 50% of all registered patients studied. On average, 1.4 adverse events occurred per patient with the somatized type, 1.0 with the affective type, 0.7 with the tonic type, and 0.4 with the phobic type.

The study showed the high effectiveness of Adepress in patients with GAD. It has been established that this drug is effective both in isolated and in GAD complicated by comorbid mental pathology. However, the results of Adepress therapy for isolated GAD are superior to the corresponding indicators in the presence of concomitant psychopathological symptoms in the structure of GAD. The results obtained are consistent with the literature that comorbid disorders in GAD complicate pharmacotherapy, requiring an increase in the drug dose and timing to achieve a therapeutic response. It should be noted that in cases of a positive response to therapy, dysthymia, obsessions, and phobias comorbid with generalized anxiety, as a rule, are reduced simultaneously with the symptoms of generalized anxiety.

The present study also showed that adepress is effective when both somatic and cognitive anxiety are dominant, however, with the predominance of somatic anxiety in the structure of GAD, the effect occurs faster - in the 3-4th week of therapy; with GAD with a predominance of cognitive anxiety, the reverse development of symptoms occurs only at 3-6 weeks of therapy.

Adepress is effective in treating patients with any clinical type of GAD, but patients with GAD of the affective and somatovegetative type are more sensitive to Adepress therapy.

The absence of significant side effects indicates that Adepress is well tolerated. In accordance with the standards for the use of modern SSRIs, the tolerability of Adepress is differentiated for different types of GAD: the frequency of adverse events decreases in the following order: somatized, affective, phobic, tonic type of GAD.

Thus, Adepress is not only effective in the treatment of various clinical variants of GAD, but is also well tolerated, which allows the drug to be considered as a first-choice treatment for this disorder.

PAROXETINE (tablets)

chii, but there is always the opportunity to purchase to order.
The cost is quite affordable - 370 rubles. I’ll tell you about the effect of the drug a little later, but now the appearance of the packaging: I bought paroxetine from the pharmaceutical company ReplekPharm, but there are other manufacturers.

The expiration date is stamped on the packaging.

The tablets themselves are small in size, film-coated, and easy to swallow with a small amount of liquid.

The instructions for the drug are frighteningly huge, the number of side effects is alarming, but I, deciding that things couldn’t get worse, dared to try this medicine.

And then the fun began. It’s good that the doctor warned that it is better to start taking pills on Friday evening, so that by the end of the new week you will become a little more human. The first day was just hell. All my worries and fears seemed to increase in volume several times. On Friday evening I just howled like a beluga. The family fled to different corners, realizing that it was better not to get caught by me. On the second day it got even worse, I was shaking like an alcoholic after a serious binge. I didn’t want to do anything, I didn’t want to eat, I didn’t want to drink, I didn’t want to do anything, I didn’t want to see anyone either. My husband rushed to call the doctor, but he reassured me that this was how it should be, you just had to be patient. But I absolutely didn’t want to endure it; it was unclear why such medications were needed if they made me feel so bad after them. Well, they persuaded me to wait another day, citing the fact that if it doesn’t go away on Sunday, then we’ll stop taking it on Monday. On Sunday it became easier, I no longer wanted to kill anyone, I just wanted to sleep. I fell asleep at lunchtime and slept without my hind legs almost until the evening. In the evening I took another pill, drank some water and continued to sleep, finally thinking that I wouldn’t get up for work tomorrow no matter what. Monday morning was the most ordinary, nothing special. Having slept well and taken another pill, I safely went to work. I was surprised that almost nothing pisses me off. Everything seems calm, and things that used to irritate me no longer bother me. I thought it was because I slept enough. I took the tablets on schedule three times a day. I was surprised to notice that practically nothing irritates me. This was the result after a week of taking the drug. I was calm as a boa constrictor after lunch. All emotional problems went away, I calmed down. I took paroxetine for two months. The doctor said that the minimum dose of the drug is one month to restore the functions of the nervous system. It is not recommended to take the medicine for less than a month, as there will be no therapeutic effect. The most important thing is that there is no “withdrawal effect”, i.e. a return to a depressive state; - a large number of side effects; - Sold only with a doctor's prescription; — the price, which is affordable at first glance, actually results in a decent amount for the entire course of treatment; — for a course of treatment you need to order at least four packages at once.

In conclusion of my review, I would like to note that our health is in our hands. Do not bring your emotional state to a critical point; it can be very difficult to recover. Take care of your nerves, no problems are worth killing yourself over. But if a problem arises and there is no way to cope on your own, there is nothing reprehensible in turning to specialists. And the most important thing is the support of loved ones. And the medicine, although scary, works. If such a drug is chosen by a doctor, then you need to take it. I give the drug four stars for the initial effect. Take care of yourself and your loved ones.