Yu. P. Sivolap’s research while affiliated with Peoples' Friendship University of Russia and other places

Antidepressants are widely used to treat depression, anxiety, insomnia, and other mental disorders. In addition, due to nonpsychotropic pharmacological effects in neurology and other divisions of clinical medicine, antidepressants are prescribed for additional indications, and in some cases they are used, including in the treatment of pain syndromes, they are used off-label. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are considered as firstline antidepressants; along with these medicines, trazodone, vortioxetine, agomelatine, bupropion and mirtazapine are often used in clinical practice. Serious prospects in the treatment of chronic pain syndrome are associated with the combined drug Dorsumio, containing the central muscle relaxant tizanidine and the antidepressant mirtazapine. The article discusses in sufficient detail the use of mirtazapine both as part of combined drug and as monotherapy, and also provides an analysis of existing approaches to switch from one antidepressant to another in the cases of insufficient efficacy or poor tolerability.

Generalized anxiety disorder and other anxiety spectrum disorders constitute the category of the most common mental disorders. Three lines of pharmacological therapy are used in the treatment of anxiety disorders: 1) selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI); 2) benzodiazepines; 3) antipsychotics. Along with SSRI and SNRI, other groups of antidepressants are used in the treatment of anxiety disorders, and other drugs with anxiolytic properties, such as pregabalin, are being considered as alternatives to benzodiazepines. Drugs in each of the three categories are characterized by both advantages and disadvantages that limit their clinical use, which determines the need to find new treatments for anxiety disorders. One of the most modern and promising treatments for generalized anxiety disorder is Aviandr, which was designated AVN-101 and CD-008-0045 at the stages of development and initial testing. The efficacy and safety of Aviandr in the treatment of generalized anxiety disorder has been proven by the results of randomized controlled trials; in addition, the effectiveness of the drug in improving the condition of patients who have suffered from acute coronavirus infection has been noted. In addition to its anxiolytic effect, Aviandr shows the ability to reduce depressive symptoms and exhibits a number of other additional effects. A notable feature of Aviandr, which gives it advantages over traditional treatments for generalized anxiety disorder with comparable effectiveness, is the absence of daytime sleepiness, which often occurs when benzodiazepines are prescribed, and the side effects that are typical for SSRI.

Objective. To present the recommendations of the expert council of the Russian Society for the Study of Pain on “Dorsumio” drug in the treatment of chronic nonspecific back pain (CNBP). Key points. Currently, CNBP is the leading disease associated with disability worldwide. Patients with CNBP often experience concomitant depressive and anxiety symptoms complicating the course of disease and therapy, as well as worsening the quality of life and working capacity. Various problems in care for CNBP include not only the impact on pathogenesis of chronic pain, but also treatment of depression, anxiety, insomnia, assessment of compatibility of various drugs and patient adherence to therapy. The new drug “Dorsumio” (mirtazapine 15 mg + tizanidine 6 mg) can influence on chronic pain mechanisms and provide effective therapy for patients with chronic nonspecific back pain due to complex analgesic, muscle relaxant, antidepressant and anti-anxiety effects.

Functional dizziness (FD) is the most common form of chronic dizziness, accounting for up to 20% of all cases of chronic dizziness and is diagnosed in 40% of patients referred to specialized clinics. This article discusses the pathogenesis, clinical manifestations and diagnostic features of FD. An overview of standard and new methods of drug therapy and methods of vestibular rehabilitation for patients with FD is provided. Experts conclude that FD, currently defined as persistent postural perceptual dizziness (PPPD), is the most common cause of chronic non-rotational dizziness. PPPD is thought to be multifactorial; central and peripheral vestibular disorders, anxiety disorders and traumatic brain injury are noted as possible precipitating causes. The diagnosis of PPPD is based on the presence of a feeling of unsteadiness or non-rotational dizziness occurring more than half of the days over a period of three months or longer, when other possible causes of dizziness have been ruled out. When managing a patient with PPPD, it is necessary to inform the patient about the nature of the disease, provide a patient with an education program and apply psychotherapy and vestibular rehabilitation methods. The use of buspirone prolonged-release tablets (Vespirate®) and vestibular rehabilitation in clinical practice is discussed.

Treatment of chronic back pain (CBP) continues to pose a pressing problem due to its nonspecificity and mixed nature. This paper presents the results of clinical trials (CT) of phases II and III on the efficacy and safety of a new drug for CBP treatment — Dorsumio (mirtazapine 15 mg + tizanidine 6 mg). Material and methods. Patients with moderate CBP and mild or moderate depression participated in CTs phase II and III. In CT phase II, a comparison was made with the original drugs mirtazapine and tizanidine, in CT phase III — with tizanidine. The primary endpoints in CTs were: a change in the severity of pain on the Numerical Rating Scale and change in the total score on the Beck Depression Scale (BDS) after 30 days of therapy (CT II) and the proportion of patients achieving ≥50% pain reduction on the NRS scale after 22 days (CT III). The secondary endpoints in CTs were: a dynamics of pain severity according to the NRS (on days 8, 15, 22, 30 in CT II), the proportion of patients with a 30% and 50% reduction in pain severity according to the NRS (on day 15 in CT II), dynamics of the total score according to the BDS (on day 30 in CT II), dynamics of the fingertip-to-floor test result (on days 15, 22, 30 in CT II), dynamics of the index according to the Oswestry disability questionnaire (at the day 30 in CT II), changes in the severity of pain according to the NRS (on days 22, 29 in CT III) in the Dorsumio and tizanidine treatment groups, the proportion of patients achieving ≥50% pain reduction according to the NRS and the dynamics of the total score on the short-form McGill Pain questionnaire (on day 29 in CT III), the dynamics of the total score according to BDS (on days 29, 56 in CT III). Results. Dorsumio significantly reduced pain severity by 86.7% compared to baseline (according to NRS) and by 74.5% compared to baseline (according to the short-form McGill questionnaire) after 30 days. Dorsumio significantly reduces the severity of pain by 50%, while the proportion of patients is 73% after 2 weeks of therapy (according to the NRS). Over the same period of therapy, the proportion of patients with a 50% reduction in pain severity in the tizanidine group was 28% less and in the mirtazapine group it was 40% less. Dorsumio significantly reduced the severity of depression by 60.5% after 4 and 8 weeks of treatment (according to the BDS). The early analgesic effect of Dorsumio in patients with CBP was significantly different from that for tizanidine and mirtazapine,and was observed after 8 days of therapy (reduction in pain severity by 38.6%). The difference in pain relief after 8 days of treatment was 13.1% when comparing changes in mean scores from baseline in the Dorsumio and tizanidine groups, and 14.3% when comparing the Dorsumio and mirtazapine groups. Dorsumio facilitated physical mobility (according to the Oswestry disability questionnaire) by 82% after a month of treatment, which is 16.4% more than in the mirtazapine group. The tolerability of Dorsumio was comparable to that of its individual components used in monotherapy.

Aim: to present the results of an expert discussion of modern aspects of the clinical manifestations, pathogenesis and treatment of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Key points. ALD and NAFLD are characterized by high prevalence and have a significant impact on public health. For the diagnosis of liver pathology, it is important to determine the stage of fibrosis and the severity of the exacerbation of the disease. In the treatment of ALD, it is recommended to achieve abstinence, proper nutrition, the appointment of B vitamins, drugs with cytoprotective activity. In severe hepatitis, corticosteroids may be prescribed. In the treatment of NAFLD, diet and lifestyle modification, weight loss, the use of insulin sensitizers, vitamin E, statins (in the presence of hyperlipidemia) and drugs with metabolic activity are effective. Currently, a point of view is being actively expressed about the synergism of the action of alcohol and the metabolic syndrome on the development of fibrosis, cirrhosis, and hepatocellular carcinoma. The current international consensus recommends a change in the nomenclature of NAFLD and ALD and proposes the terms “metabolically associated steatotic liver disease” and “metabolically associated alcoholic liver disease”. Conclusion. The closeness of the clinical manifestations and pathogenesis of NAFLD and ALD justifies attention to drugs with metabolic activity, which are recommended by the Russian Gastroenterological Association and Russian Scientific Liver Society for the treatment of these diseases. The experts support the suggestion to quantify alcohol consumption in patients with NAFLD in order to change the management of patients, if necessary.

Depression is one of the most common medical causes of disability and mortality in patients of all ages. Depressive disorders are common in the practice of physicians of a variety of specialties, including psychiatrists, neurologists, and physicians. This paper provides a summary review of the literature on modern ideas about the epidemiology, classification, and clinical picture of depression. Current approaches to the diagnosis and treatment of depressive disorders in neurological and psychiatric practice are discussed. Modern pharmacotherapeutic strategies for the treatment of depression in various patient populations are described in detail. Current clinical practice indicates the high importance of an interdisciplinary approach in the diagnosis and management of patients with depressive symptoms in Russia. The paper suggests organizational and educational strategies that can be recommended to improve the effectiveness of medical care for patients with depressive disorders.

The prolonged release tablets form of alimemazine is seen as a promising agent for the long-term treatment of generalized anxiety disorder (GAD). Objective: to investigate the efficacy and safety of therapy with alimemazine (Teraligen® retard, prolonged release film-coated tablets) in patients with GAD. Material and methods . The study design was a multicentre, open-label, non-comparative clinical trial (CT) with two doses of alimemazine 20 and 40 mg (Teraligen® retard, prolonged-release film-coated tablets). 129 patients diagnosed with GAD (criteria according to the ICD-10 classification), 86 women and 43 men were included, mean age 38.0±11.1 years. The level of anxiety, assessed by the Hamilton HARS scale, at Week 0 (Visit 1) was 24.8±7.3 points. Results. By Week 6, the level of anxiety statistically significantly decreased to a mean score of 10.8±6.6, while the dynamics of the mean score relative to baseline was -14.0±6.27 (p<0.0001). The proportion of patients with a decrease in the total score on the HARS scale by 50% or more compared with the initial value was: after 1 week of therapy – 10.3% (n=13); after 3 weeks of therapy – 60.5% (n=75; compared to baseline, p<0.0001); after 6 weeks of therapy – 69.4% (n=86; compared to baseline, p<0.0001). The therapy was well tolerated, among the adverse events (AEs) patients noted: morning sleepiness (7.8%; n=10); dry mouth (7.8%; n=10); general weakness (4.7%; n=6). Other AEs (dizziness, headache, impaired concentration, muscle weakness, memory impairment, tinnitus, tachycardia) were much less common. From the side of the liver, no AEs were detected, including changes in the activity of liver enzymes. Conclusion. Prolonged release alimemazine tablets 20 mg and 40 mg for six weeks resulted in a statistically significant reduction in anxiety levels, with at least two-thirds of patients experiencing more than half their anxiety. The effect increases with each week as you continue to take the drug. The prolonged release form of alimemazine is well tolerated, the treatment of GAD with the drug is effective and safe and may represent a rational alternative to antidepressant therapy.

A combination of depression and alcohol use disorder (AUD) is a typical and most common example of a dual diagnosis at the intersection of general psychiatry and addiction psychiatry. A comorbidity of depression and AUD is more common than it can be brought about by mere coincidence, which might be explained to some extent by the synergetic effect of both diseases, with each of them complicating the course and worsening the prognosis of the other. Treatment protocols for patients with depression and comorbid AUD include antidepressants, specific medications for alcohol dependence, and psychotherapy. The first-line antidepressants in the treatment of patients with a comorbid combination of depression and alcohol use disorder, as in other clinical situations implying use of antidepressants, are selective serotonin reuptake inhibitors (SSRIs). Fluvoxamine has certain advantages over the other SSRIs in the treatment of patients with a depression and comorbid AUD.

Alcohol withdrawal arises in result of long-lasting or short, but massive, alcohol abuse, manifests itself with oppressive symptoms and in some cases is complicated by seizures, hallucinosis and delirium tremens that may be life-threatening for patients. The leading neurochemical factors underlying alcohol withdrawal syndrome and its complications are lack of GABA and excessive glutamate activity, which is important for therapy choice. The first-line drugs in the treatment of alcohol withdrawal syndrome and alcoholic delirium are benzodiazepines, which have the maximum pharmacological similarity with ethanol. Other medications, including barbiturates, anticonvulsants, propofol, dexmedetomidine, and antipsychotics, may be used as alternatives to and in addition to benzodiazepines, especially in the case of protracted delirium with therapeutic resistance. Certain prospects in the treatment of alcohol withdrawal syndrome are associated with ethylmethylhydroxypyridine succinate, which is a bit similar to benzodiazepines in its pharmacology.