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

Paxil®

Treatment with antidepressants in children and adolescents suffering from major depressive disorder and other mental illnesses is associated with an increased risk of suicidal ideation and adverse reactions associated with suicide attempts and suicidal ideation, hostility (mainly aggression, deviant behavior and anger) were more often observed in children and adolescents receiving paroxetine than in patients in this age group who received placebo.
There are currently no data on the long-term safety of paroxetine in children and adolescents regarding the effects of this drug on growth, maturation, cognitive and behavioral development. Clinical deterioration and suicide risk in adults

Young patients, especially those with major depressive disorder, may be at increased risk of suicidal behavior during paroxetine therapy. An analysis of placebo-controlled studies in adults suffering from mental illness indicates an increase in the frequency of suicidal behavior in young patients (aged 18-24 years) while taking paroxetine compared to the placebo group: 17/776 (2.19%) vs. 5/542 (0.92%), respectively, although this difference is not considered statistically significant. In patients of older age groups (from 25 to 64 years and over 65 years), an increase in the frequency of suicidal behavior was not observed. In adults of all age groups with major depressive disorder, there was a statistically significant increase in the incidence of suicide attempts with paroxetine compared with the placebo group (incidence of suicide attempts: 11/3455 (0.32 vs. 1/1978 (0.05%), respectively. However, the majority of these cases while taking paroxetine (8 of 11) were reported in young patients aged 18 to 30. Data obtained in a study of patients with major depressive disorder may indicate an increase in the incidence of suicidal behavior in young patients, which may persist in patients over 24 years of age suffering from various mental disorders.

In patients with depression, exacerbation of the symptoms of this disorder and/or the appearance of suicidal thoughts and behavior (suncidalism) may occur regardless of whether they are receiving antidepressants. This risk persists until significant remission is achieved. The patient's condition may not improve in the first weeks of treatment or more, and therefore the patient's condition should be monitored for timely detection of clinical exacerbation and suicidality, especially at the beginning of the course of treatment, as well as during periods of dose changes, whether increasing or decreasing them. Clinical experience with all antidepressants suggests that the risk of suicide may increase in the early stages of recovery.

Other mental disorders for which paroxetine is used may also be associated with an increased risk of suicidal behavior. In addition, these disorders may represent comorbid conditions associated with major depressive disorder. Therefore, when treating patients suffering from other mental disorders, the same precautions should be taken as when treating major depressive disorder.

It must be remembered that the appearance of symptoms such as agitation, akathisia or mania can be associated both with the underlying disease and as a consequence of the therapy used.
If symptoms of clinical deterioration (including the development of new symptoms) and/or suicidal ideation and/or suicidal behavior occur, especially if they appear suddenly, increase in severity, or if they were not part of the patient's previous symptom complex, it is necessary to reconsider treatment regimen until drug discontinuation. Akathisia

Occasionally, treatment with paroxetine or another SSRI drug is accompanied by the occurrence of akathisia, which is manifested by a feeling of internal restlessness and psychomotor agitation, when the patient cannot sit or stand quietly; with akathisia, the patient usually experiences subjective discomfort. The likelihood of akathisia occurring is highest in the first few weeks of treatment.

Serotonin syndrome, neuroleptic malignant syndrome

During treatment with paroxetine, in rare cases, serotonin syndrome or symptoms similar to

neuroleptic malignant syndrome, especially if paroxetine is used in combination with other serotonergic drugs and/or antipsychotics. These syndromes may be potentially life-threatening and therefore treatment with paroxetine should be discontinued if they occur (they are characterized by clusters of symptoms such as pyrexia, muscle rigidity, myoclonus, autonomic disturbances with possible rapid changes in vital signs, mental status changes including confusion consciousness, irritability, extremely severe agitation, progressing to delirium and coma) and begin supportive symptomatic therapy. Paroxetine as L-tryptophan, oxytriptan) due to the risk of developing serotonergic syndrome.

Mania and bipolar disorder

A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not proven in controlled clinical trials) that treating such an episode with an antidepressant alone may increase the likelihood of an accelerated development of a mixed or manic episode in patients at risk for bipolar disorder.

Before initiating antidepressant treatment, careful screening should be performed to assess the patient's risk of bipolar disorder; Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Paroxetine is not registered for the treatment of depressive episodes in bipolar disorder. As with other antidepressants, paroxetine should be used with caution in patients with a history of mania.

Diabetes

In patients with diabetes mellitus, treatment with SSRI drugs may affect glycemic control. Dosage adjustments of insulin and/or oral hypoglycemic medications may be required.

cautiously 2 weeks after stopping treatment with irreversible MAOIs or 24 hours after stopping treatment with reversible MAOIs. The dose of paroxetine should be increased gradually until the optimal therapeutic effect is achieved.

Impaired kidney or liver function

Caution is recommended when treating patients with severe renal impairment or patients with impaired liver function with paroxetine.

Epilepsy

As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Seizures

The incidence of seizures in patients taking paroxetine is less than 0.1%. If a seizure occurs, treatment with paroxetine should be discontinued.

Electroconvulsive therapy

There is only limited experience with the concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma

Like other SSRI drugs, paroxetine can cause mydriasis and should be used with caution in patients with angle-closure glaucoma.

Hyponatremia

When treated with paroxetine, hyponatremia occurs rarely and mainly in elderly patients and is leveled off after discontinuation of paroxetine.

Withdrawal symptoms reported include dizziness, sensory disturbances (including paresthesia, electric shock and tinnitus), agitation or anxiety, nausea, tremor, confusion, sweating, headache and diarrhea, palpitations, emotional lability, irritability and visual disturbances.
These symptoms are usually mild or moderate, but in some patients they can be severe. They usually occur in the first few days after stopping the drug, but in very rare cases they occur in patients who accidentally miss a dose. Typically, these symptoms resolve spontaneously and disappear within 2 weeks, but in some patients they can last much longer (23 months or more). It is recommended that the dose of paroxetine be reduced gradually over several weeks or months before discontinuing it completely, depending on the needs of the individual patient. Symptoms that may occur when treatment with paroxetine is stopped in children and adolescents

In clinical studies in children and adolescents, the incidence of adverse reactions at discontinuation of treatment in patients taking paroxetine was 32%, while the incidence of adverse reactions in the placebo group was 24%.

After discontinuation of paroxetine, the following adverse reactions were recorded in at least 2% of patients and occurred at least 2 times more often than in the placebo group: emotional lability, including suicidal thoughts, suicide attempts, mood changes and tearfulness, as well as nervousness, dizziness, nausea and abdominal pain.

Bone fractures.

Based on the results of epidemiological studies of the risk of bone fractures, a connection between bone fractures and the use of certain antidepressants, including SSRI drugs, has been identified. The risk was observed during the course of treatment with antidepressants and was greatest at the beginning of the course of therapy. The possibility of bone fractures should be considered when using paroxetine.

Tamoxifen

Some studies have shown that the effectiveness of tamoxifen, as measured by the risk of breast cancer recurrence and mortality, may be reduced when coadministered with paroxetine as a result of irreversible inhibition of CYP2D6. The risk may increase with coadministration over time. When using tamoxifen for the treatment or prevention of breast cancer, the use of alternative antidepressants that do not have an inhibitory effect on the CYP2D6 isoenzyme or have it to a lesser extent should be considered.

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

Cancel paroxetine. Withdrawal symptoms have been reported to include dizziness, sensory disturbances (including paresthesia and electric shock sensations), sleep disturbances (including vivid dreams), agitation and anxiety, nausea, tremors, confusion, sweating, headaches and diarrhea. These symptoms are usually mild or moderate, but in some patients they can be severe. They usually occur in the first few days after stopping the drug, but in rare cases they occur in patients who accidentally missed just one dose. As a rule, these symptoms resolve spontaneously and disappear within 2 weeks, but in some patients they can last much longer (2-3 months or more).

As with other psychotropic drugs, abrupt withdrawal of paroxetine should be avoided. The following withdrawal regimen may be recommended: reducing the daily dose by 10 mg at weekly intervals; after reaching a dose of 20 mg/day (or 10 mg/day in children and adolescents), patients continue to take this dose for 1 week and only after that the drug is completely discontinued. If withdrawal symptoms develop during dose reduction or after discontinuation of the drug, it is advisable to resume the previously prescribed dose. Subsequently, the doctor may continue to reduce the dose, but more slowly.

The occurrence of withdrawal symptoms does not mean that the drug is abused or addictive, as is the case with narcotics and psychotropic substances.

Symptoms that may occur when treatment with paroxetine is stopped in children and adolescents. Paroxetine withdrawal symptoms (emotional lability, including suicidal thoughts, suicide attempts, mood changes and tearfulness, as well as nervousness, dizziness, nausea and abdominal pain) were reported in 2% of patients during paroxetine dose reduction or after its complete discontinuation and occurred 2 times more often than in the placebo group.

Selected groups of patients.

Elderly patients. In elderly patients, paroxetine plasma concentrations may be increased, but the range of concentrations is similar to that in younger patients. In this category of patients, therapy should begin with the dose recommended for adults, which can be increased to 40 mg/day.

Patients with impaired renal or liver function. Paroxetine plasma concentrations are increased in patients with severe renal impairment (Cl creatinine less than 30 ml/min) and in patients with impaired liver function. Such patients should be prescribed doses of the drug that are at the lower end of the therapeutic dose range.

Children under 7 years old. The use of paroxetine is not recommended due to the lack of studies of the safety and effectiveness of the drug in this group of patients.

Children and adolescents 7–17 years old. In clinical trials, adverse events related to suicidality (suicide attempts and suicidal ideation) and hostility (primarily aggression, deviant behavior and anger) were observed more often in children and adolescents receiving paroxetine than in those patients in this age group who received placebo. There are currently no data on the long-term safety of paroxetine in children and adolescents regarding the effects of this drug on growth, maturation, cognitive and behavioral development.

Clinical impairment and suicide risk associated with mental disorders. In patients with depression, worsening symptoms of the disorder and/or the emergence of suicidal thoughts and behavior (suicidality) may occur regardless of whether they are receiving antidepressants. This risk persists until significant remission is achieved. There may be no improvement in the patient's condition in the first weeks of treatment or more, so the patient must be closely monitored for timely detection of clinical exacerbation and suicidality, especially at the beginning of the course of treatment, as well as during periods of dose changes, whether increasing or decreasing them. Clinical experience with all antidepressants suggests that the risk of suicide may increase in the early stages of recovery.

Other mental disorders for which paroxetine is used may also be associated with an increased risk of suicidal behavior. In addition, these disorders may represent comorbid conditions associated with major depressive disorder. Therefore, when treating patients suffering from other mental disorders, the same precautions should be taken as when treating major depressive disorder.

Those at greatest risk for suicidal thoughts or suicide attempts are patients with a history of suicidal behavior or suicidal thoughts, young patients, and patients with severe suicidal thoughts before treatment, so all of them need to be given special attention during treatment.

Patients (and those caring for them) should be warned to monitor for worsening of their condition and/or the emergence of suicidal ideation/behavior or thoughts of self-harm and to seek immediate medical attention if these symptoms occur.

Akathisia. Occasionally, treatment with paroxetine or another SSRI drug is accompanied by the occurrence of akathisia, which is manifested by a feeling of internal restlessness and psychomotor agitation, when the patient cannot sit or stand quietly; With akathisia, the patient usually experiences subjective distress. The likelihood of akathisia occurring is highest in the first few weeks of treatment.

Serotonin syndrome/neuroleptic malignant syndrome. In rare cases, serotonin syndrome or neuroleptic malignant syndrome-like symptoms may occur during treatment with paroxetine, especially if paroxetine is used in combination with other serotonergic drugs and/or antipsychotics. These syndromes are potentially life-threatening and, if they occur, treatment with paroxetine should be discontinued (they are characterized by a combination of symptoms such as hyperthermia, muscle rigidity, myoclonus, autonomic disturbances with possible rapid changes in vital signs, mental status changes including confusion, irritability, extremely severe agitation progressing to delirium and coma) and begin supportive symptomatic therapy. Paroxetine should not be prescribed in combination with serotonin precursors such as L-tryptophan, oxytriptan due to the risk of developing serotonergic syndrome.

Mania and bipolar disorder. A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not proven in controlled clinical trials) that treating such an episode with an antidepressant alone may increase the likelihood of an accelerated development of a mixed/manic episode in patients at risk for bipolar disorder.

Before initiating antidepressant treatment, careful screening should be performed to assess the patient's risk of bipolar disorder; Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Like all antidepressants, paroxetine is not registered for the treatment of bipolar depression. Paroxetine should be used with caution in patients with a history of mania.

MAO inhibitors. Treatment with paroxetine should be started cautiously, no earlier than 2 weeks after stopping therapy with MAO inhibitors; The dose of paroxetine should be increased gradually until the optimal therapeutic effect is achieved (see also “Contraindications”).

Impaired kidney or liver function. Caution is advised when treating patients with severe renal impairment and patients with impaired liver function with paroxetine.

Epilepsy. As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Convulsive seizures. The incidence of seizures in patients taking paroxetine is less than 0.1%. If a seizure occurs, treatment with paroxetine should be discontinued.

Electroconvulsive therapy. There is limited experience with the concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma. Like other SSRI drugs, paroxetine has occasionally been associated with mydriasis and should be used with caution in patients with angle-closure glaucoma.

Hyponatremia. Hyponatremia occurs rarely during treatment with paroxetine and occurs predominantly in elderly patients.

Bleeding. Bleeding into the skin and mucous membranes (including gastrointestinal bleeding) has been reported in patients treated with paroxetine. Therefore, paroxetine should be used with caution in patients who are concomitantly receiving drugs that increase the risk of bleeding, in patients with a known bleeding tendency, and in patients with diseases predisposing to bleeding.

Heart diseases. Normal precautions should be taken when treating patients with heart disease.

Clinical experience with paroxetine suggests that it does not impair cognitive and psychomotor function. However, as with treatment with any other psychotropic drugs, patients should be especially careful when driving a car and operating machinery.

Although paroxetine does not enhance the negative effects of alcohol on psychomotor functions, it is not recommended to use paroxetine and alcohol simultaneously.

Paroxetine (Paxil) for anxiety disorders

Chakhava V.O.

Anxiety disorders (AD) develop in 25% of the population. They are often combined with each other and are comorbid with depression and various somatic diseases. TRs with comorbid conditions are usually less responsive to treatment and have a less favorable prognosis. Dysfunction of the serotonergic system has been found to play a significant role in the pathogenesis of TR, which puts forward antidepressants of the selective serotonin reuptake inhibitor (SSRI) class as first-line treatment in most cases of TR. The effectiveness of paroxetine, a representative of the SSRI, for 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 throughout life in approximately 25% of the population [1]. Despite the relatively shallow level of mental disorders, TD can significantly impair not only the subjective quality of life, but also social adaptation, as well as performance.

The main types of TD include panic disorder (PD), generalized anxiety disorder (GAD), social phobia (SSP), post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). It is important to note that when isolated, each of these conditions is less common than when accompanied by one or more other anxiety spectrum disorders. The frequency of combination of TD with depression, bipolar affective disorder, alcoholism, drug addiction and substance abuse is also high. Comorbid mental disorders worsen the prognosis of TR and complicate their treatment.

TR occurs in 30-40% of patients visiting general practitioners. In these patients, the symptoms of pathological anxiety include massive vegetative manifestations, masking the actual psychopathological symptoms. The hypochondriacal nature of many such patients prompts them to undergo multiple repeated examinations by internists, postponing the diagnosis and initiation of treatment for TR for a long time (sometimes for years).

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 [2]. 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 serotonergic system plays a decisive role in the pathogenesis of anxiety disorders [3]. It has been shown that antidepressants that suppress the reuptake of serotonin by presynaptic neurons of the central nervous system are effective in the treatment of not only depression, but also TR.

Significant progress in pharmacological research in the 1980s was marked by the development of selective serotonergic agents (SSRIs) used in modern clinical practice. Their main advantage over the so-called “classical” or “traditional” tricyclic antidepressants (“dirty drugs”) is the reduction of side effects due to the selective mechanism of action.

As a rule, anxiety disorders require long-term therapy and satisfactory patient compliance, since premature cessation of treatment often leads to exacerbation [3,4]. One of the most common reasons for 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 adherence of patients to treatment.

Paroxetine (Paxil), one of the highest-potency SSRIs, was synthesized by GlaxoSmithKline and has been used since 1992. Paroxetine is a phenipiperidine derivative and is chemically distinct from both tricyclic and tetracyclic antidepressants.

The mechanism of action of paroxetine consists of a powerful inhibition of serotonin reuptake by presynaptic receptors, desensitization of serotonin receptors, an increase in direct neurotransmission of serotonin in the intersynaptic cleft, weak inhibition of norepinephrine reuptake, as well as a mild anticholinergic effect.

The accumulated experience of clinical use of the drug confirms its high effectiveness and good tolerability in various anxiety disorders. This publication reviews the most important results from clinical trials of paroxetine in TR.

Panic disorder (PD)

The main manifestation of PR is panic attacks - attacks of sudden, extremely intense fear that arises and grows within a few minutes, accompanied by a complex of autonomic disorders (vegetative crisis - palpitations, a feeling of suffocation, sweating, dizziness). During a panic attack, patients fear sudden death, loss of consciousness, or insanity (loss of self-control). The panic attack lasts for 2-10 minutes. The frequency of panic attacks in PD varies widely: from several per day to single ones throughout the year. In some patients, PD is complicated by agoraphobia - fear and avoidance of situations with which the patient associates the occurrence of panic attacks and in which they may find themselves in a helpless position. Most often it manifests itself as a fear of riding in public transport, stuffy rooms, crowds.

According to international publications, the lifetime prevalence of panic disorder is 2-3% [12]. PD usually manifests itself between the ages of 20 and 30. In women, panic disorder develops 2-3 times more often [5].

SSRIs, particularly paroxetine, are the first choice drugs for the treatment of PD (with or without agoraphobia).

In a 12-week study of 120 patients, Ohrenberg et al. showed a significant superiority of paroxetine over placebo (p<0.05) in effectiveness, assessed by reducing the number of panic attacks [6] over 6 weeks. Paroxetine was used in a dose of 40-60 mg.

These data are confirmed by the results of a double-blind study in a larger sample (n=278), which used fixed doses of paroxetine (10, 20 and 40 mg). The most pronounced improvement was observed when paroxetine was administered at a dose of 40 mg per day, at which (and not at 10 or 20 mg) a significant superiority over placebo was revealed [7].

A 12-week, placebo-controlled, multicenter study of 367 patients with PR compared paroxetine with clomipramine and placebo. Paroxetine was ahead of clomipramine in the time of realization of the therapeutic effect: at the 9th week of treatment, the proportion of patients with complete reduction of panic attacks was significantly greater in the paroxetine group (51%) than in the clomipramine (37%) and placebo (32%) groups [7, 8]. The differences in the effectiveness of the two antidepressants disappeared only after 12 weeks of therapy. Both drugs provided a significant reduction in anxiety, agoraphobia, as well as significant improvement in indicators of work ability, social functioning and family life. However, paroxetine caused significantly fewer side effects than clomipramine.

In the prospective 9-month phase of this study, which included 176 patients with panic disorder, the proportion of patients with complete reduction of panic attacks in the paroxetine group increased to 85%, in the clomipramine group - 72%, and placebo - 59%. The significant advantage of paroxetine over placebo in this indicator remained throughout the study [9,10].

The recommended daily dose of paroxetine for panic disorder is 30-40 mg, the maximum is 60 mg/day. [eleven]. The same doses are recommended for maintenance therapy for at least 6 months after complete reduction of symptoms [11].

Generalized anxiety disorder (GAD)

The lifetime prevalence of generalized anxiety disorder is 4–6.6%. The main symptoms of GAD are anxiety and restlessness not related to specific environmental circumstances. Anxiety is provoked and intensified in connection with various, often unimportant reasons. Important symptoms of GAD include muscle tension, a feeling of stiffness, an inability to relax, and signs of autonomic hyperactivity. Most often, GAD manifests itself at the age of 18-30, usually acquires a chronic wave-like course and lasts 10 years or more.

Along with antidepressants, tranquilizers are treatments for GAD. Their use, however, is limited to short courses due to the possibility of developing tolerance and subsequent 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 patients with GAD often subsequently develop depressive states, and treatment of GAD with antidepressants, unlike the use of tranquilizers, is simultaneously preventive against depression.

The effectiveness of paroxetine in GAD was first demonstrated by Rocca et al. (1997)[12]. In an open-label, randomized study lasting 8 weeks, the authors compared 3 drugs for GAD: paroxetine, imipramine and chlordiazepoxide. The dose of paroxetine 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 (paroxetine and imipramine) were more effective. It turned out that antidepressants had a greater effect on mental symptoms of anxiety, while the tranquilizer mainly had an effect only on somatic signs of anxiety. As expected, imipramine was significantly less well tolerated than paroxetine due to anticholinergic effects (dry mouth, constipation, etc.).

Rickels et al. (2002) [13] studied paroxetine for GAD compared with placebo in an 8-week study. Paroxetine was used in doses of 20 and 40 mg. It turned out that in both doses the drug was significantly superior to placebo. However, efficacy varied depending on the dose of parksetine: at a dose of 20 mg there was a 68% responder rate, and at a dose of 40 mg there was an 81% response rate. Similar results were obtained in the study by Pollack MH et al. [14].

Paroxetine has also been effective in the long-term treatment of GAD, as well as as an anti-relapse therapy. 652 middle-aged patients with GAD were studied. It turned out that during long-term therapy with paroxetine, anxiety symptoms continued to decrease. The relapse rate in patients receiving paroxetine was significantly lower compared to placebo (10.9 vs. 39.9%). The time to relapse in the paroxetine group was also significantly longer than in the placebo group [15].

The effective daily dose of paroxetine for GAD is 20 mg, but if necessary it can be increased to 40-60 mg/day. without significant changes in safety and tolerability.

Social phobia (SSP)

SCF is manifested by a fear of being the center of attention, accompanied by fears of negative evaluation by others and avoidance of public situations.

In most cases, the disorder manifests itself between the ages of 14 and 18 years. Outbursts of anxiety are triggered by social situations, such as public speaking (exams at school, going on stage), eating in a public place, writing or talking on the phone in the presence of other people, using a public toilet. Anxiety attacks are accompanied by autonomic disorders characteristic of states of emotional stress (hot flashes, increased sweating, hand tremors, rapid heartbeat, etc.). According to epidemiological studies, the prevalence of social phobia is estimated at approximately 6%. In women, the disorder is somewhat more common.

Among the antidepressants used in the treatment of social phobia are SSRIs and reversible monoamine oxidase inhibitors (MAOIs). Clonazepam (a high-potency benzodiazepine anxiolytic) is also used.

Data on the effectiveness of paroxetine for social phobia were obtained in a double-blind, placebo-controlled study on 187 patients [16]. Paroxetine was used in a dose of 20-50 mg. Significant differences with placebo were revealed in all studied parameters, 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) paroxetine was also effective in treating social phobia [17], and the differences between paroxetine and placebo reached statistical significance also from the 4th week of treatment. Paroxetine in daily doses of 20-50 mg was well tolerated by patients.

Post-traumatic stress disorder (PTSD)

PTSD develops after exposure to a psychotraumatic factor of extreme intensity (natural disasters, terrorist attacks, acts of violence). Approximately 16% of the population experiences natural disasters. Of these, 4% develop PTSD. The incidence of PTSD is significantly higher in people who have been taken hostage. According to various authors, it is in the range of 50-100%.

Clinical manifestations include persistently recurring unpleasant memories of a traumatic event. Increased physiological reactivity to internal or external stimuli that symbolize or resemble traumatic events. Patients attempt to avoid thoughts, feelings, or conversations related to the trauma and make efforts to achieve such avoidance. There is a noticeable decrease in interest or participation in previously meaningful activities, and a feeling of isolation or alienation from others. Some people complain of being “unemotional”—a limited range of feelings (for example, an inability to experience feelings of love). Among the symptoms of increased excitability, the most typical are difficulty falling asleep or early awakening, irritability or outbursts of anger, and difficulty concentrating. Increased alertness, hypervigilance, constant anticipation of a threat, and fearfulness bring PTSD closer to other anxiety spectrum disorders.

Despite the fact that the concept of PTSD was developed more than a quarter of a century ago, research on the effectiveness of pharmacotherapy for this disorder is still scarce. To date, 3 large placebo-controlled studies have been conducted on the effectiveness of paroxetine in PTSD [18,19]. These were 12-week studies where paroxetine was used at a dose of 20-40 mg. The results were similar. According to a meta-analysis of these studies, paroxetine therapy was effective in 57% of patients, significantly superior to placebo (39%). The effect of the drug was noted in relation to all the main signs of PTSD.

Obsessive-compulsive disorder (OCD)

The main manifestations of OCD are obsessive thoughts and actions. OCD is one of the most severe non-psychotic disorders. The disease is usually chronic, significantly complicating daily activities. By obsessive we usually understand mental manifestations that arise in the psyche independently and against desire, unexpectedly, and often suddenly, without direct connection with the content of thinking. It is impossible to free yourself from obsessions through a conscious volitional effort; they interfere with the correct flow of thoughts and slow it down. At the same time, patients retain a critical attitude towards obsessions, which distinguishes them from “overvalued” and delusional ideas.

The lifetime prevalence of OCD is approximately 2%. The disease manifests itself gradually after a long latent phase, lasting up to 10 years. The onset of the disease usually occurs between the ages of 14 and 24 years. OCD tends to have a persistent, chronic course, often being drug-resistant and significantly impairing daily activities.

A number of studies have proven the decisive role of serotonin mechanisms in the development of OCD. It is clear that among the pharmacotherapeutic agents for the treatment of OCD, serotonergic antidepressants are primarily used - primarily SSRIs and clomipramine. Moreover, the treatment of OCD requires higher doses of drugs than the treatment of depression, and the effect of treatment appears later. Reduction of symptoms is observed 3-4 weeks after the start of therapy.

A 12-week placebo-controlled trial in 348 patients with OCD compared paroxetine 20, 40 or 60 mg with placebo [20]. Paroxetine was significantly more effective than placebo at all doses studied. Interestingly, in more severely ill patients the response to paroxetine 60 mg was better than that of 40 and 20 mg.

Another 12-week randomized trial compared paroxetine with clomipramine and placebo [21]. The dose of paroxetine could vary in the range of 10-60 mg, clomipramine - 25-250 mg. The study involved 406 patients. Significant differences from placebo were recorded at week 6 in both the paroxetine and clomipramine groups. A 25% reduction in symptoms was observed in 55% of patients in both groups. Not surprisingly, paroxetine was much better tolerated than clomipramine. Refusals to continue therapy were only 9% (in the clomipramine group - 17%), the rate of adverse events was 16% (in the clomipramine group - 28%).

In long-term treatment, paroxetine has also shown to be effective. In a long-term (12-month) follow-up study involving 104 patients with OCD, the use of paroxetine significantly reduced the frequency of exacerbations compared to placebo [22].

Doses of paroxetine for the treatment of OCD are usually 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 [22].

Literature

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2. Rouillon, F.: Depression comorbid with anxiety or medical illness: The role of paroxetine. Int. J. Psychiat. Clin. Practice 5, 3-10 (2001).

3. Ballenger, JC: Selective serotonin reuptake inhibitors in panic disorder. In: Selective Serotonin Reuptake Inhibitors. (2nd edition) (Eds.: Feighner J. P, Boyer, W.), Wiley, Chichester, 1996. pp. 155-178.

4. Mavissakalian, M, Perel, J.: Protective effects of imipramine maintenance treatment in panic disorder with agoraphobia. Amer. J. Psychiatry 194, 1053-1057 (1992).

5. Kessler, RC, et al.: Lifetime and 12month prevalence of DSM-III-R psychiatric disorders in the United States. Arch. Gen. Psychiatry, SI, 8-19. (1994)

6. Oehrberg, P.E. et.al. Paroxetine in the treatment of panic disorder: a randomized, doubleblind, placebo-controlled study. pit. J. Psychiatry 167, 374-379, (1995). 16. Ballenger, JC, Wheadon, DE, Steiner, M., Bushnell, W., Gergel, IP: Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. Amer. J. Psychiatry 155, 36-42, (1998).

7. Mavissakalian, M, Perel, J.: Clinical experiment in maintenance and discontinuation of imipramine in panic disorder with agoraphobia. Arch. Gen. Psychiatry 49, 318-323 (1992).

8. LeCrubier, Y., Bakker, A., Judge, R. and the Collaborative Paroxetine Study Investigators: A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Acta Psychiat. Scand. 95, 145-152. (1997).

9. Dunbar, G. C., Judge R.: Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Eur. Neuropsychopharmacol. 5, 361, Abstract P5-27, (1995).

10. LeCrubier, Y., Judge, R. and the Collaborative Paroxetine Study Investigators: Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Acta Psychiat. Scand. 95, 153-160. (1997).

11. Dunner, D, Kumar, R: Paroxetine: a review of clinical experience. Pharmacopsychiat. 3, 189-201 (1998).

12. Rocca, P., Fonzo, P., Scotta, M., Zanalda, E., Ravizza, L.: Paroxetine efficacy in the treatment of generalized anxiety disorder. Acta Psychiat. Scand. 95, 444-450 (1997).

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