Venlafaxine (Velaxin) - the most effective antidepressant?

Venlafaxine (Velaxin) - the most effective antidepressant?

Summary

Evidence-based medicine has failed to provide convincing evidence that antidepressants differ in their effectiveness in treating depression. Therefore, scientists base their judgments about the effectiveness of drugs on “personal experience.” There is another way to determine the most effective antidepressant. To do this, it is necessary to compare data on the activity of neurons in depression and the ability of antidepressants to affect these neurons. This comparison suggests that the most effective antidepressants are amitriptyline, imipramine and venlafaxine (in high daily doses). But only venlafaxine is used in our country in therapeutic doses. Therefore, venlafaxine is the most effective antidepressant.

Persistent attempts by pharmaceutical companies, using evidence-based medicine, to confirm that their antidepressant is the most effective in treating depression have so far been unsuccessful. Not only individual critics of such studies agree with this, but also large teams of scientists who draw up recommendations for the pharmacotherapy of depressive disorders. In any case, they proceed from the fact that evidence-based medicine indicates comparable activity of antidepressants in the treatment of depression (1, 2, 3). Therefore, to determine the most effective drugs, scientists resort to the “personal experience” accumulated during the treatment of patients (4), which is always subjective. This method of determining the most effective antidepressants is vulnerable to criticism. An alternative to “personal experience” is to compare the mechanisms of depression formation (pathogenesis) and the medicinal properties of drugs.

It is known that symptoms of depression are accompanied by a decrease in the activity of various neurons: norepinephrine (↓N), dopamine (↓D), serotonin (↓C) and melatonin (↓M) (Table 1).

Table 1. Reduced neuronal activity in different symptoms of depression (5, 6, 7).

The main of these symptoms, reflecting deterioration (decrease) in mood (3, 6), are associated with deterioration in the functioning of norepinephrine and dopamine (↓ND), norepinephrine and serotonin (↓SN), as well as serotonin, norepinephrine and dopamine neurons (↓SND). Accordingly, all depressions can be divided into three classes. The first of these includes ↓ND depression. They occur with a weakening of positive emotions. The second option covers ↓HF depression. They are characterized by increased negative emotions. Finally, the third one includes ↓SUD-depression. They are accompanied by both a weakening of positive and an increase in negative emotions. With all three of these types of depression, phenomena of psychomotor retardation (↓H-symptoms) and/or somatic symptoms (↓SND or ↓SUI) may be observed. From the presented data it follows that for the successful treatment of any depression it is necessary to increase the activity, first of all, of norepinephrine, dopamine and serotonin neurons (↑SND). Accordingly, this is exactly how the most effective antidepressants should act. In other words, they must be ↑SND drugs.

To increase the activity of serotonin, norepinephrine and dopamine neurons, antidepressants have only three mechanisms. They can be neurotransmitter reuptake inhibitors (NRRIs), agents affecting regulatory receptors (ARRIs), or drugs that reversibly inhibit monoamine oxidase type A (MAO-A) (Table 2).

Table 2. Antidepressants known in Russia, their effect on neurons and the “formula” of the mechanism of action (4, 5, 6, 8).

*- white color – the drug does not affect neurons, dark gray – a pronounced increase in activity, light gray – a moderate increase in activity,

**- in high doses

However, the overwhelming majority of antidepressants used in Russia are classified as IOPs (Table 2). It is this pharmacological property that determines the ability to activate neurons in 66.7% of drugs related to tricyclic (TCA) and quadricyclic (TCA) antidepressants, as well as selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) . Three more drugs (14.3%) combine the properties of IOP and SVRR. Trazodone (serotonin modulating antidepressant - SMA), milnacipran (SNRI) and vortioxetine (multimodal antidepressant - MMA) have such a mixed mechanism of action.

A similar situation is observed throughout the world. Most antidepressants are IODs. For example, in the United States, these include 8 of the 10 most commonly prescribed drugs (duloxetine, desvenlafaxine, citalopram, setralin, fluoxetine, escitalopram, paroxetine, venlafaxine) (9). Another one, vilazodone, combines the property of an IOP with a different mechanism of action. In some countries (for example, in the USA), the reputation of IOPs is so high that they try not to register antidepressants that do not have this mechanism of action at all (10).

IOHs are not only allowed into the medical services market as a priority, but they are also considered a kind of “standard”. After all, their mechanism of action leaves neurotransmitters (serotonin, norepinephrine or dopamine) where they usually realize their effects - “between” neurons in the so-called. “intersynaptic gap” (5). As a result, serotonin, norepinephrine, or dopamine act on nerve cells for a longer time, and neurons fire more than usual. It is also important that this mechanism of action is completely reversible, since it does not promote the creation of new neurotransmitters (their synthesis) and does not inhibit their breakdown (metabolism). And this is very important for the safety of treatment.

But not all antidepressants are strong IODs (4, 5). For some drugs, this mechanism of action is much less pronounced (Table 2). Thus, pipofesin (TcA), which is indicated only for mild to moderate depression (11), most likely moderately activates serotonin, norepinephrine and dopamine neurons. Trazodone (SmA) and vortioxetine (MmA) are serotonin IODs (Table 2). But this mechanism of action is less pronounced in them compared to SSRIs (4, 12).

Antidepressants may be strong SRIs only for serotonin (SSRI: sertraline, paroxetine, citalopram, escitalopram, fluoxetine, fluvoxamine, TCA: clomipramine), norepinephrine (SA: maprotiline; SNRI: milnacipran) or both of these neurotransmitters (TCA: amitriptyline, imipramine; SNRIs: venlafaxine and duloxetine) (4, 5, 13, 14). With regard to dopamine, all modern drugs are only weak IOPs (TCA: amitriptyline, imipramine, clomipramine, pipofezin; SNRIs: venlafaxine in high daily doses), or do not act at all on the metabolism of this neurotransmitter (4, 5, 6, 13, 14) . In addition, for some IODs, the potential to affect different nerve cells is dose dependent (7).

Thus, venlafaxine (SNRI), especially in low daily doses (75-150 mg), is more of a serotonin IOI and affects serotonin neurons. At the same time, it has an active metabolite, desvenlafaxine. This substance is itself an antidepressant abroad, and its properties differ from venlafaxine. Desvenlafaxine is a strong IOR of serotonin and norepinephrine, and in high doses is a weak IOR of dopamine. The amount of desvenlafaxine is considered to be half the prescribed daily dose of venlafaxine. As the dosage of the latter increases, the concentration of its active metabolite in the blood also increases. Accordingly, venlafaxine, prescribed at a dose of 150-225 mg/day, due to desvenlafaxine is converted into an IOP of serotonin and norepinephrine. As a result, it effectively activates serotonin and norepinephrine neurons (Table 2). If the daily dose is increased further, then venlafaxine (together with desvenlafaxine) will acquire the properties of dopamine IOZ. Then the drug will activate not only serotonin and norepinephrine neurons, but also dopamine neurons, although much weaker (Table 2).

Moving now to SVRR (mianserin - ChsA, mirtazapine - norepinephrine and selective serotonin antidepressant - NaSSA, agomelatine - melatonergic antidepressant) we will point out the reason why they are inferior, at least to strong IOs, in the effectiveness of their action on neurons (Table 2 ). With the help of RR, it is not the excitation of nerve cells that is carried out, but rather the “fine-tuning” of their “tone” (5, 8, 15). Therefore, “pure” SVRRs are quite rare among antidepressants.

But there are many IOPs whose effect on RR is an additional mechanism of action. But due to its relative weakness, it is not even mentioned in drug instructions (16, 17, 18). For example, milnacipran (SNRI) is a serotonin and norepinephrine SRI (16). This property gives the antidepressant the ability to effectively activate norepinephrine neurons and, more weakly, serotonin neurons (6). At the same time, milnacipran, due to its effect on RR, promotes a moderate increase in the “tone” of dopamine nerve cells (19). However, this property is not mentioned in the instructions for the drug. And only for some IOIs the effect on RR is still mentioned in the guidelines for the medical use of antidepressants. This feature is characteristic of trazodone (SmA) and vortioxetine (MmA) (5, 8, 20). Both antidepressants are serotonin IRIs. This property allows them to moderately activate serotonin neurons (Table 2). And due to their effect on RR, they slightly increase the “tone” of norepinephrine and dopamine nerve cells.

Finally, two more drugs (OIMAO-A: pirlindole and moclobemide) to activate neurons depress (inhibit) the work of the enzyme - monoamine oxidase, which destroys neurotransmitters (serotonin, norepinephrine, dopamine) (5, 20, 21, 22, 23), as inside neurons and outside them - in the intersynaptic cleft. It would seem that this mechanism of action should be very strong, because as a result, the amount of serotonin, norepinephrine and dopamine increases both inside and outside the neuron. However, this effect is typical primarily for the so-called. irreversible monoamine oxidase inhibitors that form stable chemical bonds with this enzyme (24). After this, it can no longer perform its functions and disintegrates, and instead the body is forced to synthesize a new enzyme, which usually takes about two weeks. As a result, irreversible monoamine oxidase inhibitors are indeed highly active antidepressants. However, due to the high efficiency of their mechanism of action, they are poorly tolerated and can even be toxic, and their use in our country has practically ceased.

A different picture is observed in the case of pirlindole and moclobemide (20, 22). The effect of these drugs on the enzyme is reversible (MAOI). The fact is that their connection with the enzyme is only relatively stable. Its gradual disappearance leads to the release of monoamine oxidase, while the enzyme itself remains intact (24). In addition, pirlindole and moclobemide selectively inhibit the activity of only one of the types of monoamine oxides - “A” (OMAO-A), while the other type “B” continues to work almost with the same strength. All these features significantly reduce the effectiveness of OIMAO-A, which is why the mechanism of action under consideration is much less common than IOI (Table 2). At the same time, these features make OIMAO-A more tolerable drugs that weakly activate serotonin, norepinephrine and dopamine neurons.

The presented features of the mechanisms of action of antidepressants can be represented in the form of a letter formula consisting of the first letters of the name of the neuron on which it acts (↑с, ↑н, ↑н, ↑м). Moreover, in the case of pronounced activation of the nerve cell, you can use a capital letter (↑С, ↑Н, ↑Д, ↑М), and in case of weak activation, a lowercase letter (↑с, ↑н, ↑д, ↑м). An individual “formula” of the mechanism of action of an antidepressant is obtained (hereinafter simply “formula”), which reflects its pharmacological activity much more accurately than the name of the group.

Such “formulas” indicate the existence of “triple” action drugs. These include:

• ↑SNd antidepressants (active effect on serotonin and norepinephrine neurons and weaker on dopamine neurons): amitriptyline (TcA),
• Imipramine (TCA)
• venlafaxine (SNRI) in high daily doses

There are drugs with “dual” action. These include:

• ↑SN-antidepressants (active effect on serotonin and norepinephrine neurons): duloxetine (SNRI)
• venlafaxine (SNRI) in average daily doses

Finally, “single” action drugs include:

• ↑C-antidepressants (active effect on serotonin neurons): sertraline (SSRI),
• paroxetine (SSRI),
• citalopram (SSRI),
• escitalopram (SSRI),
• fluoxetine (SSRI),
• fluvoxamine (SSRI).

The presented data makes it easy to determine that the most effective will be “triple” action antidepressants, whose formula contains the largest number of capital letters. These are ↑SNd antidepressants that actively affect serotonin and norepinephrine neurons and weaker on dopamine neurons: amitriptyline (TcA), imipramine (TcA), venlafaxine (SNRI) in high daily doses. This set of pharmacological properties allows them to influence all three types of depression (↓ND with weakening of positive emotions; ↓CH with increased negative emotions; ↓SND-depression with weakening of positive and increased negative emotions), which can be accompanied by symptoms of psychomotor retardation (↓ H-symptoms) and/or somatic symptoms (↓SND or ↓SUM).

The presented very short list of the most effective antidepressants correlates well with the “personal experience” of foreign experts creating recommendations. It was already mentioned above that TCA and SNRIs are recognized as the most powerful drugs there (4). Some recommendations contain more precise instructions. It reports that, along with TCAs, only one SNRI, venlafaxine, is the most effective (3). But experts always make a reservation that they cannot provide any objective evidence of their point of view. One can only regret that they did not want to address the peculiarities of the formation of symptoms of depression and the mechanism of action of antidepressants. If we take into account the relationships between them, then the “personal experience” of experts becomes quite understandable and even “public.”

The analysis performed puts venlafaxine in an exceptional position, especially in our country. It is well known that in Russia TCAs (amitriptyline and imipramine) are prescribed very “sparingly” in low doses, which, as a rule, are less than therapeutic ones (25, 26). This is due to the pronounced side effects characteristic of amitriptyline and imipramine. Meanwhile, any drug, including TCA, when prescribed in doses that do not reach the therapeutic range, loses its effectiveness. As a result, in our country only venlafaxine can claim to be the most effective antidepressant. And this drug is widely used in our country in the form of Velaxin (Egis). It was recommended by leading scientific organizations conducting advanced research in the field of psychiatry. Among them are the Federal State Budgetary Institutions “State Scientific Center for Social and Forensic Psychiatry named after V.P. Serbsky" and "Moscow Research Institute of Psychiatry" of the Russian Ministry of Health, St. Petersburg Research Institute named after. V.M. Bekhterev (27, 28). Long-acting capsules (Velaxin retard) are also well known (29), with the use of which there is a significant reduction in the frequency of such side effects of the drug as nausea (30). In addition, the study of Velaxin was successfully carried out not only in psychiatry, but also in neurology (31). It remains to be recommended to use this antidepressant as widely as possible in the treatment of depression.

A video by M.Yu. Drobizhev on the same topic can be viewed at the link:

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M.Yu. Drobizhev, Doctor of Medical Sciences, Head of the Educational Department of the Educational Center of the Association of Medical and Pharmaceutical Universities of Russia

Contact Information -

E.Yu. Antokhin, Candidate of Medical Sciences, Associate Professor, Head of the Department of Clinical Psychology and Psychotherapy of the Orenburg State Medical University of the Russian Ministry of Health.

R.I. Palaeva is an assistant at the Department of Clinical Psychology and Psychotherapy at the Orenburg State Medical University of the Russian Ministry of Health.

S. V. Kikta, Candidate of Medical Sciences, Head. Department of the Federal State Budgetary Institution "Polyclinic No. 3" of the Administration of the President of the Russian Federation, Moscow

Use of velafax in patients with comorbid depression and anxiety

Depressive and anxiety disorders are the two most common groups of mental disorders. Thus, about 19% of the population exhibits signs sufficient to diagnose a depressive episode, and 17% of the general population meets criteria for an anxiety disorder (Kessler RC et al., 1994). A similar pattern is observed among outpatients in both psychiatric (Bradley N. et al., 2007) and general medical institutions (Zing W. et al., 1990). About 2/3 of patients diagnosed with major depression show signs sufficient to diagnose a current anxiety disorder (Zimmerman M. et al., 2000).

The coexistence of symptoms of anxiety and depression has important therapeutic and prognostic significance, since this group of patients is more likely to experience a chronic course of the disease and more severe impairments in social and everyday functioning (Liebowitz MR, 1993, Lyddiard RB, 1991). The presence of anxiety in people with major depression increases the risk of suicide attempts (Placidi GP et al., 2000; Scocco P. et al., 2000, Schaffer A. et al., 2000). Recognizing the coexistence of depression and anxiety is an important factor in determining the optimal treatment. However, until recently, clinical trial designs often excluded patients with comorbid conditions. This has led to the fact that in practice, the choice of drug for therapy in people with comorbid pathology continues to be very difficult, since it is based on data from studies of the spectrum of action of drugs in people with so-called “pure disorders”. It is this fact that makes the study of the effectiveness and safety of antidepressants, especially drugs of the latest generations, in patients with coexisting anxiety and depression undeniable relevance.

In the era of classic antidepressants, only 20–30% of patients with symptoms meeting DSM-IY criteria for major depression sought medical help. This was partly due to the perception among patients that available treatments for depression were “subjectively unpleasant” due to the development of side effects (Angst J., 1990). The need to reduce side effects and increase the effectiveness of therapy has led to the emergence of selective serotonin reuptake inhibitors (SSRIs), which have proven effective against both major depression, dysthymia, and most types of anxiety disorders. However, serotonin reuptake inhibitors turned out to be less effective than tricyclic antidepressants against severe forms of vital depression (Danish University Antidepressant Group, 1990, Anderson IM, 1998), which led to the search for chemical compounds with multiple but specific mechanisms of action. Clinical and experimental experience initiated the creation of the drug venlafaxine (velafax, manufactured by Pliva), which is a mixed norepinephrine and serotonin reuptake inhibitor, devoid of influence on other neurotransmitter systems. According to clinical studies, venlafaxine was not only more effective in relieving symptoms of moderate depression compared to imipramine (Lecrubier Y. et al., 1997), but also in relation to severe depressive symptoms compared to fluoxetine (Clerc GE et al., 1994 ). Velafax has shown its effectiveness in the treatment of depressive disorders of mild and moderate severity, including those with a pronounced anxiety component (Volel B.A., Romanov D.V., 2007). Among the latest generations of antidepressants, venlafaxine has demonstrated the best dose-response relationship, which is obviously due to the fact that in small therapeutic doses (75–125 mg) venlafaxine acts as a serotonin reuptake inhibitor with a simultaneous minimal effect of norepinephrine reuptake, but however, the norepinephrine effect increases when increasing doses to 150–375 mg. However, the side effect profile of venlafaxine is approximately equivalent to that of an SSRI.

The high efficacy and safety of venlafaxine have led to the fact that this drug is used as a standard or reference drug in many comparative studies. At the same time, in Russia, drugs whose active ingredient is venlafaxine (including the drug velafax, produced by the Pliva company) appeared only a few years ago, which gives research into their therapeutic characteristics undoubted interest and relevance.

STUDY PROCEDURE

A 12-week open-label post-marketing study aimed to investigate the effectiveness of velafax on depressive and anxiety symptoms, clinical global impression, and tolerability and safety in patients experiencing a “depressive episode” (F32), “recurrent depressive disorder” (F33) or “mixed anxiety and depressive disorder” (F41.2) according to ICD-10 criteria. In this case, a necessary condition for inclusion in the group of subjects was the severity of depressive symptoms corresponding to 20 points or more on the Hamilton Depression Scale (HAM-D21), and the level of anxiety in accordance with the Hamilton Anxiety Scale (HAM-A) had to be ≥ 20 points. Only those patients whose clinical severity score according to the CGI-S was ≥ 4 were included in the study.

The study design involved 4 visits (inclusion visit, third, sixth and 12th weeks of therapy). During the visits, the severity of depression was assessed using the 21 Item Hamilton Depression Rating Scale (HAM-D21) and the Montgomery Asberg Depression Rating Scale (MADRS), the severity of anxiety was assessed using the Hamilton Anxiety Rating Scale (HAM-A), as well as the determination of general clinical impressions using Clinical Global Impression Severity of Illness (CGI-S) and Improvement (CGI-I). Tolerability of the study drugs was assessed at the 3rd and 4th visits. The study did not include persons with established hypersensitivity to the study drug, alcohol abusers, moderate and severe forms of renal and liver failure, and uncompensated forms of diabetes mellitus. Exclusion criteria also included opioid use, pregnancy and lactation, the presence of comorbid psychotic diseases, the patient's current risk of suicide, and age under 18 years.

The optimal dose was selected individually in accordance with clinical data. The starting dose of velafax ranged from 75 to 150 mg per day, divided into two doses. Dosage increases of 37.5–75 mg were allowed every two to three days until response to therapy was achieved. The maximum daily dose was 375 mg. The study design allowed, if necessary, the use of benzodiazepine anxiolytics during the first three weeks of taking velafax, followed by a gradual reduction in dosage by the fourth week of use, as well as the use of benzodiazepines, imidazopyrine anxiolytics and hypnotics for sleep disorders throughout the study period.

Before the start of the study, written informed consent to participate in the study was obtained from patients.

Statistical processing of the obtained data was carried out using the Statistika 6.0 program (StatSoft, USA).

MATERIALS

In a study conducted in the department of geriatric psychiatry of the St. Petersburg Psychoneurological Research Institute named after. V.M. Bekhterev, 30 patients were included (11 inpatient and 19 outpatient): 10 men and 20 women aged from 21 to 72 years. The average age of the patients was 54.1 ± 6.32 years. The condition of 6 patients included in the study group met the criteria for a depressive episode (F32), 25 patients suffered from recurrent depressive disorder (F33) ICD-10. The level of depressive symptoms at the time of inclusion in the study in patients was 25.54 ± 3.85 HAM-D21 points, 30.10 ± 6.70 MADRS points, which corresponds to a severe depressive episode. Our sample did not include persons with an established diagnosis of “mixed anxiety and depressive disorder,” however, the severity of anxiety measured by HAM-A was 21.06 ± 3.28 points, which is sufficient for diagnosing an anxiety state. The average severity of the disease was 4.32 ± 0.77 points on the CGI-S.

11 (33%) patients had confirmed concomitant somatic pathology, while out of 10 patients suffering from coronary heart disease and hypertension, 8 were constantly taking β-blockers, calcium channel blockers or antihypertensive drugs. Two patients included in the study had gastrointestinal pathology, but the patients' condition did not require concomitant therapy.

The initial dose of velafax in 12 patients was 75 mg, in 18 patients – 150 mg, the dosage was determined by the severity of depressive symptoms. The effective dose was maintained until the end of observation (12 weeks of therapy). The average dose of the drug at the end of the study was 256.9 ± 81.0 mg per day.

RESULTS

Of the 30 patients included in the study, 27 patients (90.0%) completely completed the 12-week course of taking Velafax. Two patients (10.0%) dropped out of the study during the first three weeks of taking the drug for the following reasons: 1 patient (3.2%) due to severe nausea with a good therapeutic response, 1 patient refused to continue participation due to an increase in blood pressure numbers and fears of developing decompensation of hypertension with increasing dosages. One (3.2%) patient was withdrawn from the study in the sixth week of taking velafax due to the ineffectiveness of high-dose therapy.

During the study, there were no reasons for adjusting the doses of drugs for the treatment of concomitant somatic pathologies; no signs of drug interactions or complications of the course of existing somatic diseases were identified. In 2 patients with gastrointestinal pathology (chronic gastritis), no adverse events were observed. Among the side effects noted during the period of taking velafax, 2 (6.4%) young male patients with a good therapeutic effect experienced moderate sexual dysfunction, which, however, did not lead to refusal to take therapy. Tolerability of the drug assessed at the third and fourth visits was defined as “good”, “very good” or “excellent” in all patients.

Five patients, upon inclusion in the study, were taking benzodiazepine tranquilizers or hypnotics due to severe sleep disorders, the need for which disappeared as their condition stabilized (end of the 3rd week of taking velafax).

Analysis of the data obtained during the study allows us to state a reduction in symptoms of depression and anxiety in patients included in the study. The results of statistical processing of data from the psychometric scales HAM-D21, HAM-A, MADRS are presented in Fig. 1 (parameters with significant differences are presented, p < 0.0001).

As follows from the data presented in Fig. 1, the level of anxiety and depression in patients included in the study, measured using the HAM-D21, HAM-A, MADRS scales, decreased, while significant differences in the severity of symptoms were observed between the first and second, second and third, third and fourth visits. all of the above scales. At the same time, by the 12th week of taking velafax, the average level of depression at the end of the study in our sample, the average score on HAM-D21 was 5.7 ± 3.45, on MADRS – 6.89 ± 4.80, which corresponds absence of depressive symptoms. It should be noted that the dynamics of Hamilton Depression Scale scores in our sample varied among patients of different age subgroups. Thus, in patients under 50 years of age, a rapid reduction in depressive symptoms was observed: 10 out of 12 patients (83%) in this age category could be classified as responders by the 3rd week of admission, since the level of depressive symptoms in accordance with HAMD decreased by more than 50 %. By the 12th week of taking Velafax, 93% of patients under 50 years of age achieved remission. At the same time, in patients over 50 years of age, a slower decrease in the severity of symptoms was noted; by the 6th week of treatment, only 65% ​​of patients in this age subgroup could be classified as responders, but by the end of the study, 83% of patients over 50 had reached remission years.

Of particular interest is the dynamics of parameters identified as the so-called. “key factor” and “anxiety/somatization factor”, as well as a reflection of one’s own depressive and actual anxiety components of the depressive state. The dynamics of the parameters that make up the key factor are presented in Fig. 2.

As follows from the data presented in Fig. 2, the values ​​of the parameters “depressive mood”, “feeling of guilt”, “impaired performance”, “lethargy” differed significantly between the inclusion visit and the 6th week of admission (second visit), significantly decreased between the 3rd and 6th, 6 1st and 12th weeks of therapy (first, second and third visits, respectively). The value of the “suicidal thoughts” variable significantly decreased between the inclusion visit and the 3rd week of taking velafax (first visit) and subsequently did not have any significant differences.

The dynamics of the parameters of the “anxiety/somatization” factor are presented in Fig. 3.

As follows from the data presented in Fig. 3, the level of mental and somatic anxiety, the severity of gastrointestinal and somatic symptoms differed significantly between the inclusion visit and the 3rd week of admission (first visit), 3rd and 6th, 6th and 12th weeks of administration of velafax (first , second and third visit respectively). Significant differences in the values ​​of the parameter “hypochondria” and “attitude to the disease” were found between the third and sixth, sixth and twelfth weeks of taking Velafax.

In our sample of patients, a gradual decrease in the severity of the disease was observed, as evidenced by significant differences in the CGI-S scale indicators between the start of treatment and the third week of taking velafax, the third and sixth, sixth and twelfth weeks of taking velafax, while simultaneously changing the parameters of general improvement with the most pronounced significant changes in CGI-I scores between the 3rd and 6th weeks of admission (first and second visit, respectively).

THE DISCUSSION OF THE RESULTS

Treatment of patients with symptoms of depression and anxiety in the clinical picture continues to present significant difficulties, despite the significant arsenal of drugs currently available to the practitioner. Often in clinical practice, the effectiveness of antidepressants in relation to anxiety and depressive symptoms is lower than demonstrated by clinical studies, due to the fact that simple extrapolation of data obtained from studying the effectiveness and safety of drugs in patients with “pure conditions” introduces certain difficulties in the issues of choosing the optimal drug for the treatment of patients with comorbid depression and anxiety. That is why studies of the effectiveness and safety of antidepressant drugs, especially the latest generation of drugs, in this category of patients do not lose their relevance.

The purpose of our study was to study the therapeutic activity and tolerability of velafax in patients whose condition fell within the framework of a depressive episode or recurrent depressive disorder ICD-10. Our sample consisted of individuals whose severity of depressive symptoms at the time of inclusion in the study, assessed using the 21 Item Hamilton Depression Rating Scale (HAM-D21) and Montgomery Asberg Depression Rating Scale (MADRS), met the criteria for a major depressive episode. At the same time, the severity of anxiety, assessed by the Hamilton Anxiety Rating Scale (HAM-A), was sufficient to diagnose an anxiety state, which allows us to classify the patients included in our sample as individuals with comorbid depression and anxiety.

Our data allows us to state the fact that velafax is sufficiently effective not only in relation to depressive symptoms themselves, but also anxiety coexisting with depression, as evidenced by changes in the parameters of psychometric scales assessing the severity of anxiety. Noteworthy is the synchronicity and harmony of the decrease in the level of depressive and anxiety symptoms when taking Velafax in patients in our sample. The dynamics of the indicators of the psychometric scales we used indicate the presence of a significant difference in the level of severity of anxiety and depression already by the third week of taking velafax compared to the beginning of the study, which indicates the rapidity of the onset of the therapeutic effect.

It is worth noting some features of the effect of velafax on psychopathological symptoms in different age groups. Thus, the number of responders among young patients by the third week of taking the drug was more than 80%, which is consistent with the data available in the literature on the high rate of onset of the effect of velafax (Volel B.A., Romanov D.V., 2007). At the same time, in patients over 50 years of age, the therapeutic effect occurred more slowly; only by the 6th week of treatment the number of responders was about 65%. At the same time, by the time the study was completed, the average level of severity of depressive symptoms and anxiety in our sample corresponded to the state of remission in both age subgroups. This kind of dynamics of the onset of a therapeutic effect is not unexpected, since it is characteristic of elderly patients, especially when using selective serotonin reuptake inhibitors and tianeptine, and to a lesser extent amitriptyline (Andrusenko M.P., 2003).

At the same time, it should be emphasized that the significant degree of severity of psychopathological symptoms led to relatively high average effective dosages of the drug; more than 50% of patients received maximum or submaximal doses of velafax, while in all patients who completely completed the study, tolerability was characterized as “good”, “very good” and “excellent”. The low percentage of patients who dropped out of the study indicates the high effectiveness and good tolerability of velafax.

Thus, the results of our study showed the high therapeutic efficacy of velafax against severe depression and anxiety, which, along with a favorable tolerability profile and a high level of safety, may serve as a basis for the use of velafax in patients with comorbid anxiety and depressive disorders.

Bibliography

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Velaxin®

Depression increases the risk of suicidal thoughts and suicide attempts. This risk persists until stable remission occurs. Therefore, patients should be under constant medical supervision and should be given only small quantities of the drug capsules to reduce the risk of possible abuse and/or overdose. Velaxin® should not be used in the treatment of children and adolescents under 18 years of age. An increase in the likelihood of suicidal behavior (suicide attempt and suicidal ideation), as well as hostility, was observed more often in clinical trials among children and adolescents receiving antidepressants compared with groups receiving placebo.

Aggressive behavior has been reported while taking venlafaxine (especially at the beginning of treatment and after discontinuation of the drug).

The use of venlafaxine may cause psychomotor restlessness, which clinically resembles akathisia, characterized by restlessness with a need to move, often combined with an inability to sit or stand still. This is most often observed during the first few weeks of treatment. If these symptoms occur, increasing the dose may have an adverse effect and the advisability of continuing to take the drug should be considered.

Like all antidepressants, venlafaxine should be prescribed with caution to patients with a history of mania and/or hypomania, as the drug may cause an increase in their symptoms. In these cases, medical supervision is necessary.

Caution should be exercised when treating patients with a history of seizures. If convulsive seizures occur or their frequency increases, treatment with venlafaxine should be interrupted.

Like selective serotonin reuptake inhibitors, venlafaxine should be used with caution when used concomitantly with antipsychotic drugs, as symptoms resembling neuroleptic malignant syndrome may develop.

Patients should be warned to seek immediate medical attention if rash, hives, or other allergic reactions occur.

Some patients experienced a dose-dependent increase in blood pressure while taking venlafaxine, and therefore regular monitoring of blood pressure is recommended, especially at the beginning of treatment or when increasing the dose.

Isolated cases of orthostatic hypotension have been described while taking venlafaxine. Patients, especially the elderly, should be warned about the possibility of dizziness and impaired balance.

Venlafaxine may cause an increase in heart rate, especially at high doses. Particular caution should be exercised when prescribing the drug to patients with conditions that may be aggravated by an increase in heart rate.

There are insufficient studies of the use of venlafaxine in patients who have recently suffered a myocardial infarction or suffering from decompensated heart failure, so this drug should be used with caution in these patients.

Like other serotonin reuptake inhibitors, venlafaxine may increase the risk of bleeding into the skin and mucous membranes, so caution is required when treating patients predisposed to bleeding.

Hyponatremia and/or syndrome of insufficient antidiuretic hormone secretion (SIADH) may occur while taking venlafaxine, especially in conditions of dehydration or decreased blood volume (including in elderly patients and patients taking diuretics).

Cases of mydriasis have been reported while taking venlafaxine, so patients with a predisposition to increased intraocular pressure or those at risk of angle-closure glaucoma require careful medical monitoring.

In case of renal and liver failure, special caution is required. In some cases, a dose reduction is required (see section "Method of administration and dosage").

The safety and effectiveness of using venlafaxine with weight-loss drugs, including phentermine, have not been established, so their simultaneous use (as well as the use of venlafaxine as monotherapy for weight loss) is not recommended. Clinically significant increases in serum cholesterol levels have been observed in some patients receiving venlafaxine for at least 4 months. Therefore, when taking the drug for a long time, it is advisable to monitor serum cholesterol levels.

After stopping the drug, especially abruptly, withdrawal symptoms often occur (see section “Side effects”). The risk of withdrawal symptoms may depend on several factors, including course length and dose, and the rate of dose reduction.

Withdrawal symptoms such as: dizziness, sensory disturbances (including paresthesia and electrical sensations), sleep disturbances (including insomnia and unusual dreams), agitation or anxiety, nausea and/or vomiting, tremor, sweating, headache, diarrhea, rapid and increased heart rate, and emotional instability are usually mild to moderate in severity, but may be severe in some patients. They are usually observed in the first days after discontinuation of the drug, although there have been isolated reports of such symptoms in patients who accidentally missed a dose. Usually these phenomena resolve on their own within 2 weeks; however, in some patients they may be longer lasting (2-3 months or more). Therefore, before discontinuing venlafaxine, it is recommended to gradually reduce its dose over several weeks or months, depending on the patient's condition (see sections "Dosage and Administration").