Anxiety Disorder (TR)
Anxiety disorders (TR) develop in 25% of the population. They are often combined with each other, are comorbid with depression and various somatic diseases. TR with comorbid conditions are usually worse treatment and have a less favorable prognosis. A significant role of serotonergic system dysfunction has been found in the pathogenesis of TR, which advances antidepressants in the class of selective serotonin reuptake inhibitors (SSRIs) as a first-line therapy in most cases of TR. The effectiveness of paxil, a representative of SIOZS, with TR is confirmed by the results of numerous randomized studies.
The results of epidemiological studies indicate that anxiety disorders are among the most common forms of mental pathology, occurring in the life of approximately 25% of the population. Despite the relatively shallow level of mental disorders, TRs can significantly impair not only the subjective quality of life, but also social adaptation, as well as efficiency.
The main types of TR are panic disorder (PR), generalized anxiety disorder (GAD), social phobia (SCF), post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). It is important to note that in isolation, each of these conditions is less common than when accompanied by one or more other disorders of the anxiety spectrum. The frequency of combining TR with depressions, bipolar affective disorders, alcoholism, drug addiction, and substance abuse is also high. Comorbid mental disorders worsen the prognosis of TR and impede their therapy.
TR occurs in 30-40% of patients seeking general practitioners. In these patients, the symptoms of pathological anxiety include massive vegetative manifestations, masking the actual psychopathological symptoms. The hypochondria, inherent in many such patients, encourages them to repeated examinations of internists, postponing the diagnosis for a long time (sometimes for years) and the start of treatment for TR.
It should also be noted that TR is often combined not only with other mental disorders, but also with somatic diseases such as duodenal ulcer, coronary heart disease, arterial hypertension, rheumatoid arthritis, bronchial asthma. According to epidemiological studies, in patients with TR, these somatic diseases are detected much more often than in the general population.
As a result of numerous studies, it has been established that the decisive role in the pathogenesis of anxiety disorders belongs to the serotonergic system. It has been shown that antidepressants that suppress serotonin reuptake by presynaptic neurons of the central nervous system are effective in treating not only depression, but also TR.
Significant progress in the field of pharmacological research in the 1980s was marked by the development of selective serotonergic drugs (SSRIs) used in modern clinical practice. Their main advantage over the so-called “classic” or “traditional” tricyclic antidepressants (“dirty drugs”) is to reduce side effects due to the selective mechanism of action.
As a rule, anxiety disorders require long-term therapy and satisfactory patient compliance, since premature discontinuation of treatment often leads to exacerbation. One of the most common causes of premature discontinuation of therapy is the development of unwanted side effects. The favorable tolerability profile of SSRIs due to the high degree of selectivity of their action contributes to good tolerability and, as a result, significantly greater patient adherence to treatment.
Paxil (Paroxetine) – one of the highest potential SSRIs was synthesized in GlaxoSmithKline and has been used since 1992. Paxil is a derivative of phenipiperidine and is chemically different from both tricyclic and tetracyclic antidepressants.
The mechanism of action of paxil consists of potent inhibition of serotonin reuptake by presynaptic receptors, desensitization of serotonin receptors, an increase in direct neurotransmission of serotonin in the inter-synaptic gap, weak inhibition of the reuptake of noradrenaline, and also mild anticholinergic action.
The accumulated experience of the clinical use of the drug confirms its high efficacy and good tolerance in various anxiety disorders. This publication discusses the most important clinical findings of paxil in TR.
Panic Disorder (PR)
The main manifestation of PR – panic attacks – attacks of sudden extremely intense fear that arises and increases within a few minutes accompanied by a complex of vegetative disorders (vegetative crisis – heartbeat, feeling of suffocation, sweating, dizziness). During a panic attack, patients are afraid of sudden death, loss of consciousness or insanity (loss of control over themselves). Panic attack continues within 2-10 minutes. The frequency of panic attacks in PR varies widely: from a few per day to a single per year. In some patients, PR is complicated by agoraphobia – fear and avoidance of situations with which the patient associates the occurrence of panic attacks and in which he may be in a helpless position. Most often manifested fear of driving in public transport, stuffy rooms, the crowd.
In accordance with the data of international publications, the prevalence of panic disorder throughout life is 2-3%. Usually OL manifests between the ages of 20 to 30 years. In women, panic disorder develops 2-3 times more often.
SSRIs, in particular, paxil, are the drugs of first choice in the treatment of PR (with or agoraphobia).
As part of a 12-week study involving 120 patients, Ohrenberg et al. showed a significant superiority of paxil over placebo (p <0.05) in efficacy, as measured by reduction in the number of panic attacks over 6 weeks. Paxil was used in a dose of 40-60 mg.
These data are confirmed by the results of a double-blind study on a larger sample (n = 278), which used fixed doses of paxil (10, 20, and 40 mg). The most pronounced improvement was noted when prescribing paxil at a dose of 40 mg per day, at which (and not at 10 or 20 mg) a significant advantage over placebo was detected.
According to a 12-week placebo-controlled multicenter study involving 367 patients with PR, paxil was compared with clomipramine and placebo. Paxil was ahead of clomipramine in terms of the therapeutic effect: on the 9th week of treatment, the proportion of patients with complete reduction of panic attacks was significantly higher in the paxil group (51%) than in the clomipramine group (37%) and placebo (32%). Differences in the effectiveness of the two antidepressants disappeared only after 12 weeks of therapy. Both drugs provided a significant reduction of anxiety, agoraphobia, as well as a significant improvement in the indices of working capacity, social functioning and family life. At the same time, paxil caused significantly fewer side effects than clomipramine.
In the prospective 9-month phase of this study, in which 176 patients with panic disorder participated, the proportion of patients with complete reduction of panic attacks in the paxil group increased to 85%, in the clomipramine group – 72%, and placebo – 59%. Paxil’s significant advantage over placebo for this indicator persisted throughout the study.
The recommended daily dose of paxil for panic disorder is 30-40 mg, maximum – 60 mg / day. The same doses are recommended for maintenance therapy for at least 6 months after complete reduction of symptoms.
Generalized Anxiety Disorder (GAD)
The prevalence of generalized anxiety disorder throughout life is 4-6.6%. The main symptoms of GAD are anxiety, anxiety, not associated with certain environmental circumstances. Anxiety is provoked and aggravated due to various, often insignificant causes. Important symptoms of GAD are muscle tension, stiffness, inability to relax, and signs of autonomic hyperactivity. More often, GAD manifests at the age of 18-30, usually acquires a chronic undulating course and lasts 10 or more years.
Along with antidepressants, treatment of GAD are tranquilizers. Their use, however, is limited to short courses due to the possibility of developing tolerance and the subsequent formation of drug dependence. It is believed that this probability is less than in the treatment of PR, but it must also be taken into account. In addition, it is known that GAD patients often develop depressive states later on, and GAD therapy with antidepressants, unlike the use of tranquilizers, is at the same time prophylactic against depression.
For the first time, the effectiveness of paxil with GTR was shown by Rocca et al. (1997). In an open, randomized study of 8 weeks, the authors compared with GAD 3 drugs: buy paxil online, imipramine and chlordiazepoxide. The dose of paxil was 20 mg, imipramine – 50-100 mg, chlordiazepoxide – 3-6 mg. The study showed that in the first 2 weeks the benzodiazepine tranquilizer chlordiazepoxide had an advantage over antidepressants in reducing anxiety, but from the 4th week antidepressants (paxil and imipramine) were more effective. It turned out that antidepressants had a greater effect on the mental symptoms of anxiety, and the tranquilizer mainly affected only the somatic signs of anxiety. As expected, imipramine was significantly worse than paxil due to anticholinergic effects (dry mouth, constipation, etc.).
Rickels et al. (2002) studied paxil for GAD versus placebo in an 8-week study. Paxil was used in doses of 20 and 40 mg. It turned out that in both doses, the drug was significantly superior to placebo. However, the effectiveness varied depending on the dose of parksetin: in the dose of 20 mg of responders there were 68%, and in the dose of 40 mg – 81%. Similar results were obtained in the Pollack M.H. study. et al.
Paxil was also effective in the long-term treatment of GAD, as well as a means of anti-relapse therapy. 652 patients of middle age with GAD were studied. It turned out that throughout the lengthy treatment with paxil, the alarming symptoms continued to decrease. The recurrence rate in patients treated with paxil was significantly lower compared with placebo (10.9 vs. 39.9%). The time to relapse in the paxil group was also significantly longer than in the placebo group.
The effective daily dose of paxil with GAD is 20 mg, but if necessary it can be increased to 40-60 mg / day. no significant change in safety and portability.
Social Phobia (SCF)
SCF is manifested by the fear of being in the center of attention, accompanied by fears of a negative assessment of others and avoiding public situations.
In most cases, the disorder manifests between the ages of 14-18. Outbreaks of anxiety are provoked by social situations, for example, during public speaking (exams at school, going to the stage), eating in a public place, writing or talking on the phone in the presence of other people, using the public toilet. Anxiety attacks are accompanied by vegetative disturbances characteristic of states of emotional stress (hot flushes, increased sweating, hand tremor, rapid heartbeat, etc.). According to epidemiological studies, the prevalence of social phobia is estimated at about 6%. In women, the disorder is more common.
Of the antidepressants used in the treatment of social phobias, SSRIs and reversible monoamine oxidase inhibitors (AIMA) are used. Also clonazepam (high potential benzodiazepine anxiolytic) is used.
Data on the effectiveness of paxil with social phobia were obtained in a double-blind, placebo-controlled study on 187 patients. Paxil was used in a dose of 20-50 mg. Significant differences with placebo emerged in all parameters studied, starting from the 4th week of therapy, and persisted until the end of the study. In a similar study with a sample of 290 patients, Baldwin et al. (1999) paxil was also effective in social phobias, with the differences between paxil and placebo reaching a degree of statistical significance also from the 4th week of treatment. Paxil in daily doses of 20-50 mg was well tolerated by patients.
Post Traumatic Stress Disorder (PTSD)
PTSD develops after exposure to a traumatic factor of extreme intensity (natural disasters, terrorist acts, acts of violence). Approximately 16% of the population faces natural disasters. Of these, 4% get PTSD. The incidence of PTSD is significantly higher among those who have been held hostage. According to different authors, it is in the range of 50-100%.
Clinical manifestations include constantly recurring unpleasant memories of a psycho-traumatic event. The physiological reactivity to internal or external stimuli, which symbolize traumatic events or have similarities with them, increases. Patients attempt to avoid thoughts, feelings or conversations related to trauma, and make efforts to avoid them. There is a noticeable decrease in interest or participation in previously significant activities, a sense of isolation or alienation from others. Some complain of their “insensitivity” – limiting the range of feelings (for example, the inability to experience a feeling of love). Among the symptoms of increased excitability are most characteristic violation of falling asleep or early awakening, irritability or outbursts of anger, difficulty concentrating. Increased vigilance, supervigilance, constant expectation of threat, fearfulness bring PTSD closer to other disorders of the anxiety spectrum.
Although the concept of PTSD was developed more than a quarter of a century ago, studies of the effectiveness of pharmacotherapy in this disorder are still scarce. To date, 3 large placebo-controlled studies of the efficacy of paxil in PTSD have been conducted. These were 12-week studies where paxil was used at a dose of 20-40 mg. The results were similar. According to a meta-analysis of these studies, paxil therapy was effective in 57% of patients, significantly exceeding placebo (39%). The effect of the drug was noted in relation to all major signs of PTSD.
Obsessive Compulsive Disorder (OCD)
The main manifestations of OCD are obsessive thoughts and actions. OCD is among the most severe non-psychotic disorders. The disease usually flows chronically, significantly complicating daily activities. Under the obsessive it is customary to understand the mental manifestations that arise in the psyche independently and against desire, suddenly, and often suddenly, are not directly related to the content of thinking. It is impossible to get rid of obsessions by conscious volitional effort, they impede the correct flow of thoughts and inhibit it. At the same time, patients retain a critical attitude to obsessions, which distinguishes them from “overvalued” and delusional ideas.
The prevalence of OCD over a lifetime is about 2%. It manifests the disease gradually after a long latent phase lasting up to 10 years. The onset of the disease usually occurs at the age of 14-24 years. OCD has a tendency to persistent chronic course, often detecting resistance to drug effects and significantly complicating daily activities.
In a whole series of studies, the crucial role of serotonin mechanisms in the development of OCD has been proved. It is clear that among the pharmacotherapeutic agents for the treatment of OCD, serotonergic antidepressants are used primarily – first of all, SSRIs and clomipramine. Moreover, for the treatment of OCD requires higher doses of drugs than in the treatment of depression, and the effect of treatment appears later. Symptom reduction occurs 3-4 weeks after initiation of therapy.
In a 12-week placebo-controlled study involving 348 patients with OCD, paxil was compared in doses of 20, 40, or 60 mg and placebo. Paxil was significantly more effective than placebo in all doses studied. Interestingly, in more severe patients, the response to paxil therapy at a dose of 60 mg was better than at 40 and 20 mg.
In another 12-week randomized trial, paxil was compared with clomipramine and placebo. The dose of paxil could vary in the range of 10-60 mg, clomipramine – 25-250 mg. The study involved 406 patients. Significant differences from placebo were recorded on the 6th week in both the paxil group and the clomipramine group. 25% reduction in symptoms was observed in 55% of patients in both groups. Not surprisingly, paxil was tolerated much better than clomipramine. Refusals to continue therapy were only 9% (in the clomipramine group, 17%), the incidence of adverse events was 16% (in the clomipramine group, 28%).
With long-term treatment, paxil also showed its effectiveness. During a long (12-month) follow-up study involving 104 patients with OCD, the use of paxil significantly reduced the frequency of exacerbations compared with placebo.
Doses of paxil in the treatment of OCD usually make up 40-60 mg per day; if necessary, the dose can be increased to 80 mg / day. The recommended minimum duration of maintenance therapy after remission is 1 year.