[Ethical-deontological problems of therapy of mental disorders]. / Etiko-deontologicheskie problemy terapii psikhicheskikh rasstroistv.

In recent decades, psychiatric ethics has been an area of intensive research and reconsideration of established regulations. Basic principles of medical deontology do not cover ethical issues of modern psychiatric science and practice. The fundamental principle of ethical relationship between a physician and a patient in psychiatric practice is a voluntary informed consent that is based on three main criteria: voluntarism, decision-making capacity and information disclosure about proposed medical procedure. The principle of voluntary informed consent implies a dialogue between a psychiatrist and a patient that rely on the principles of patient's autonomy and does not allow the priority of the paternalistic approach. The physician is obliged to provide all available information on the proposed intervention in a comprehensive way and assess the degree of patient's awareness of this information. The main objective is to determine patient's ability to make decisions as accurately as possible. Many mental disorders affect cognitive processes of decision making and may impact patient's autonomy. It is unacceptable to consider psychiatric patients as incapable of making decisions in advance.

[The risk of developing cardiovascular disease in bipolar disorder. Biological factors and therapy].

BACKGROUND: Bipolar disorder (BD) is one of the most common mental disorders characterized by alternating episodes of mania/hypomania and depression, as well as the possibility of developing mixed conditions. Correct and timely diagnosis of BD is important due to the presence of a high suicidal risk and a high predisposition to the development of cardiovascular disease (CVD). The risk of CVD is higher in ВD than in other mental disorders. MATERIALS AND METHODS: A sample assessment was made of current studies focusing on the vascular-bipolar link. The search was carried out in the PubMed and eLIBRARY databases for the following keywords: bipolar disorder, psychopharmacology, cardiovascular disease, biological mediators. RESULTS: There are several biological factors which explain the close association and common pathogenetic mechanisms of BD and CVD. The most interesting of them are inflammation, oxidative stress, and brain-derived neurotrophic factor. Neuroimaging methods have shown similar structural brain changes in people with BD and with CVD. There is some evidence of the efficacy of statins and angiotensin-converting enzyme inhibitors in reducing cardio-vascular risk factors in BD patients. CONCLUSION: The predisposition of patients of BD to CVD is beyond doubt. It is necessary to consider the peculiarities of the course of BD and conduct active monitoring and preventive measures to reduce the risk of developing life-threatening CVDs. Further research focused on the pathogenetic relationship between BD and CVD could provide more insight into this area.

[The risk of developing cardiovascular disease in bipolar disorder. Clinical and social factors].

Bipolar disorder (BD) is one of the most common mental disorders in the world with high mortality and a hard economic burden. Although suicide is the leading cause of death in BD, cardiovascular disease (CVD) also contributes significantly to this rate, the risk of which is seriously underestimated in BD. A sample assessment was made of current studies focusing on the link between BD and CVD. The search was carried out in the PubMed and eLIBRARY databases for the following keywords: bipolar disorder, psychopharmacology, cardiovascular disease, metabolic syndrome. The association between BD and vascular disease is large. The analysis of adjusted mortality estimates in patients with bipolar disorder showed a significant contribution of CVD. A detailed study of the mutual influence of bipolar disorder BD and CVD is difficult due to the earlier manifestation of BD in comparison with CVD. Most of the studies have focused on cardiovascular risk factors (CVRFs), which are more common in BD than in the general population. Metabolic syndrome (MS) plays a significant role among CVRFs. The reasons for the development of MS in patients with BD are currently not known for sure, however, the instigated factors are certainly a disturbance of the diet, decreased physical activity, pharmacological therapy, and the lack of early preventive and medical care. Patients with hyperuricemia had a higher risk of developing MS. Lifestyle correction and a reduction of CVFRs, as well as the rational use of certain cardiac drugs can improve the better prognosis of the disease and reduce mortality in patients with BD. The predisposition of patients with BD to CVD is undeniable. It is necessary to consider the high frequency of CVRFs in people with BD, and promptly recommend appropriate treatment and special rehabilitation programs for the prevention of CVD complications, considering the change in affective phases and the applied mood-stabilizing drugs.

[Problems of mental health in the situation of COVID-19 pandemic]. / Problemy psikhicheskogo zdorov'ya v usloviyakh pandemii COVID-19.

The WHO declared COVID-19 pandemic, the deterioration of the epidemic situation in Russia, the lockdown and the growing fear in society caused by panic rumors and misinformation spread on social networks and the media pose urgent organizational and medical tasks for our psychiatric service. Based on the experience of other countries that have already encountered the massive spread of COVID-19, the author presents a review of the proposed urgent and preventive organizational and treatment measures and suggests practical recommendations on urgent temporary reorganization of the psychiatric service, and the provision of psychological and psychotherapeutic support to the most vulnerable groups of the population, including medical personnel working with patients with COVID-19, and the management of mentally ill patients with severe acute respiratory syndrome. As the primary goals, it is proposed to separate the flows of people in need of psychological support and psychiatric care, and organize the remote provision of these services (hotline phones and telemedicine consultations). Particular attention is paid to the management of mentally ill patients with coronavirus respiratory syndrome and the characteristics of psychopharmacological therapy with an overview of the potential risks of side-effects and complications related primarily to respiratory function, including those due to adverse drug interactions.

[Effect of Lurasidone on symptoms of schizophrenia in five-factor dimensional model: pooled analysis of two short-term, randomized, double-blind, placebo-controlled studies in patients from Russia and Ukraine]. / Ispol'zovanie piatifaktornoi dimensional'noi shkaly simptomov shizofrenii dlia otsenki terapevticheskogo deistviia Lurazidona: ob''edinennyi analiz dannykh dvukh kratkosrochnykh randomizirovannykh dvoinykh slepykh platsebo-kontroliruemykh issledovanii na populiatsii patsientov Rossii i Ukrainy.

AIM: Evaluation of a new five-factor dimensional model of schizophrenia in recent revisions of classifications of mental disorders (DSM-5 and ICD-11) dictates the need to use this approach in conducting a comprehensive assessment of the effectiveness of new antipsychotic agents, including ethnically homogeneous populations of patients. MATERIAL AND METHODS: Post-hoc analysis of pooled data from two randomized, double-blind, placebo-controlled, 6-week clinical studies (RCTs) of lurasidone (fixed doses, 40, 80, 120 or 160 mg/d) in patients experiencing an acute exacerbation of schizophrenia. Changes in PANSS total score, CGI-S score and five established PANSS factors were assessed using mixed-model repeated measures analysis. RESULTS: Lurasidone (n=162, dose groups pooled) compared with placebo (n=68), significantly improved the PANSS total score at Week 6 (-23.0 vs. -10.5; p<0.001; effect size 0.82) as well as all PANSS factor scores: positive symptoms (-8.5 vs. -4.2; p<0.001; effect size 0.88), negative symptoms (-4.4 vs. -2.8; p=0.011, effect size 0.44), disorganized thoughts (-4.4 vs. -2.1; p<0.001; effect size 0.70), hostility/excitement (-2.7 vs. -0.7; p<0.001; effect size 0.66), and depression/anxiety (-3.5 vs. -2.2; p=0.002; effect size 0.53). CONCLUSION: Lurasidone demonstrated significant improvement for both PANSS total score and each of the five PANSS factor scores, indicating effectiveness across the broad spectrum of schizophrenia symptoms. Effect size for both PANSS total score and each of the five PANSS factor scores for the local population was higher than for the wider population, which included patients from various countries.

[Daily dynamics of time perception in bipolar II disorder patients with redarted or anxious depression]. / Dnevnaya dinamika vospriyatiya vremeni pri zatormozhennoi i trevozhnoi depressii u bol'nykh bipolyarnym rasstroistvom II tipa.

AIM: It is known affective disorders are changing the perception of time. The study of time perception in patients with affective disorders enables researchers to make early diagnostic criteria for these conditions, as well as to shed light on possible mechanisms for the development of affective disorders. MATERIAL AND METHODS: 20 patients with bipolar affective disorder type II in accordance with the DSM-5 criteria (10 patients with a predominance of anxiety and 10 patients with a predominance of psychomotor retardation) and 10 healthy subjects were recruited to the study. Test for measuring minute was conducted from 7 hours to 21 hours with an interval of 2 hours. Patients were distributed into two experimental groups in accordance with the severity ratio of psychomotor retardation and anxiety. All patients were on monotherapy with agomelatine in a single dose 25-50 mg/day. RESULTS AND CONCLUSION: Duration of individual minute, was significantly shorter in the experimental groups compared with the control group and did not differ within experimental groups. In the group of healthy volunteers length of individual minutes was close to «AIM: minute, i.e. 60 seconds, in groups of patients with prevalence of anxiety and a predominance of psychomotor retardation length of individual minutes was set to about 40 seconds and did not differ significantly in patients groups. In patients with retarded depression distribution of a minute duration peaks was shifted for 2 hours late (13-17 h) comparing to controls, in anxious depresssion the distribution was bimodal with peaks in 10 and 18 hours. There were no singnificant differences between groups. Shorter duration of individual minute in patients with recurrent depressive episodes, may be an early sign of a new depressive episode.

[EEG spectral characteristics in resistant depression patients on transcranial magnetic stimulation treatment].

OBJECTIVE: to examine the EEG spectral characteristics during TMS in resistant depression therapy. MATERIAL AND METHODS: The sample consisted of 32 depressive patients diagnosed with recurrent depressive disorder or bipolar affective disorder. TMS, as well as EEG, were conducted during the previous inefficient thymoanaleptic therapy with reduced doses. TMS was performed in the left prefrontal cortex. Treatment course consisted of 15 procedures with 100% threshold intensity. During a single procedure, the patient received 20 cycles of stimulation pulses with the frequency of 15 Hz, duration of 20 seconds and interval of 60 seconds between single cycles. EEG was recorded with the use of the «NEURO-KM¼ apparatus (Russia) with band pass from 0.5 to 45 Hz and time constant of 0.3 sec before and after the course of TMS. Spectroscopic analysis of EEG was conducted using the Fast Furies Transformation analysis with average of no less than 30 periods for 2 seconds with subsequent mapping with the use of the «BRAINSYS¼ system (Russia). RESULTS AND CONCLUSION: After conducting TMS, EEG changes were generalized and included the reconstruction of all frequencies of the electrical brain activity. However, the major changes were seen in alpha-rhythm spectrums: its index increased in all cortical areas, mostly in the occipital cortex, thereby forming the alpha-rhythm focus in these areas.

[A comparative study of different types of pharmacotherapy in treatment of depressive phase of bipolar II disorder]. / Varianty farmakoterapii depressivnoi fazy bipoliarnogo affektivnogo rasstroistva tipa II.

OBJECTIVE: A comparative evaluation of the efficacy and safety of different types of pharmacotherapy: antidepressant monotherapy (agomelatine or sertraline), mood stabilizer monotherapy (valproate) and combination therapy (valproate + sertraline) in bipolar II disorder patients with major depressive episode. MATERIAL AND METHODS: A 6-week open randomized study included 89 inpatients and outpatients. Basic criteria of efficacy were ≥50% reduction of HAMD total score and remission (≤7 points) to the end of the study. RESULTS: At the end of the study (day 42), the highest number of patients with 50% reduction of HAMD total score was noted in the sertraline (65%) and combination therapy (60%) groups, in the valproate group it was 57.1%, and the lowest - in agomelatine group (42.9%), but the differences were not statistically significant. Remission was observed in 45% patients in combination therapy group compared with 33.3% in valproate group, 32.1% in agomelatine group and only 20% in group of sertraline, but the differences between the groups also were not significant. CONCLUSION: Antidepressants (agomelatine and sertraline) have demonstrated fast but insufficient influence on the reduction of depression in the patients. Treatment with sertraline rarely led to remission and was frequently associated with high rate of switch into hypomania. Valproate therapy was moderately effective and well-tolerated without risk of switching. Combination of valproic acid with sertraline had the highest efficacy and was fairly well tolerated.

Validation of the Russian version of the Hypomania Checklist (HCL-32) for the detection of Bipolar II disorder in patients with a current diagnosis of recurrent depression.

BACKGROUND: There are no validated screening tools for Bipolar Disorder (BD) in Russia. OBJECTIVE: To validate the Russian version of the HCL-32 for the detection of Bipolar II disorder (BD II) in patients with Recurrent Depressive Disorder (RDD). METHODS: 409 patients with a current diagnosis of RDD were recruited. The diagnosis was confirmed by the validated Russian version of the Mini International Neuropsychiatric Interview (MINI). Another investigator interviewed the patients using the НСL-32 questions. RESULTS: The total HCL-32 score in patients with BD II was significantly higher than in patients with RDD: 18.2 (4.22) versus 10.85 (5.81) (p<0.001, d=1447). At the cut-off 14 points the sensitivity was 83.7%, specificity 71.9% (p<0.001). The Cronbach's alpha was 0.887 that means good internal consistency. The best discrimination was achieved with 8 items: decreased need for sleep, less shyness or inhibition, talkativeness, more jokes and puns, jumping thoughts distractibility, exhausting or irritating others and high and more optimistic mood. We proposed the reduced variant of the scale, that includes only these 8 variables, with sensitivity 90.5%, specificity 69.8% (AUC=0.88). CONCLUSIONS: The Russian version of the HCL-32 displayed a good ratio of sensitivity to specificity and can be recommended as a validated screening instrument. An 8-item version of HCL needs further research. LIMITATIONS: Limitations include the specific nature of the sample, the HCL-32 assessment carried out by a psychiatrist, no comparison with other BD screening scales. The results of the 8-item version may be sample and culture dependent.

[Current biological hypotheses of recurrent depression (review)].

A review of the recent data on the biological mechanisms of depression, including the мonoamine hypothesis, the diathesis-stress model and the chronobiological model, is presented. These and other biological hypotheses are viewed in the aspect of the current genetic, neurochemical and neuroimaging studies as well as in relation to different treatment approaches. Depression seems not to be a homogenous disease and may be caused by different factors. Genetic factors and stressful life events play an important role in the young age. Chronic stress, chronobiological disturbances and comorbid somatic disease are relevant to middle-aged and elderly people. Moreover, recurrent and chronic depression are accompanied by cognitive impairment, social dysfunction and neurodegeneration. All these factors should be taken into consideration in the development of personalized complex treatment programs.

[Modern treatment of a depressive phase (review)].

The analysis of modern Russian and world literature on the diagnosis and treatment of a depressive phase of bipolar affective disorder (BAD) is presented. Studies on the efficacy of different groups of drugs (antidepressants, mood stabilizers, antipsychotics) used in the treatment of bipolar disorders are reviewed. Expert views on the treatment of bipolar disorders are discussed.

[The use of mGlu2/3 receptors as a new approach to treat schizophrenia: results of a randomized double-blind trial].

Glutamate neurotransmission has been considered as one of pathogenetic factors of schizophrenia though all antipsychotics widely used in modern psychiatric practice are dopamine antagonists. LY2140023 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors with antipsychotic effect. In the present study, we have assessed clinical efficacy of LY2140023 in patients with schizophrenia compared to the control group receiving olanzapine in a randomized double-blind placebo-controlled trial. The statistically significant reduction of positive and negative symptoms measured with the PANSS (p<0.001) was observed for both antipsychotics at week 4 of treatment compared to placebo. The treatment with LY2140023 was safe and well-tolerated; treated patients did not differ from the placebo group by hyperprolactinemia and extrapyramidal symptoms, and weight gain. The results suggest that the agonist for 2/3 (mGlu2/3) receptors has antipsychotic properties and provides a new, alternative to dopamine agonists, method for pharmacotherapy of schizophrenia.

[Open randomized comparative twelve-week study of lithium and valproate in manic episode].

One hundred and twenty-five patients (49 men and 76 women, mean age 38,0+/-12,5 years) were randomized in two groups. One group (64 patients) was treated with valproate sodium and another group (61 patients) received lithium carbonate. Monotherapy was administered with the mean dose of valproate 20 mg/kg/day (serum valproate concentration between 70 and 125 ?g/ml) and the mean dose of lithium 800 mg/day (between 600 and 900 mg/day; serum lithium concentration 0,8-1,2 mmol/L) during 12 weeks. Clinical effectiveness was assessed using YMRS, CGI-BP and MADRS at 0, 5th, 10th, 21st , 84th days of treatment. The number of responders (50% reduction in YMRS scores) was 51,7% (30 patients) in lithium group and 56,7% (34 patients) in valproate group by the 21st day (p=0,59).The mean reduction in YMRS scores was 11,6 in patients treated with lithium and 12,3 in patients treated with valproate. By the 84th day (LOCF), the number of responders reached 85% (51 patients) in lithium group and 90,3% (56 patients) in valproate group (p=0,37). The mean reduction in YMRS scores was 19,4 in patients treated with lithium and 19,6 in patients treated with valproate. The average reduction in MADRS scores was -1,4 (p=0,08) and -2,2 (p=0,001) in lithium group; -1,6 (p=0,002) and -1,4 (p=0,019) in valproate group on the 21st and 84th days. Adverse effects were observed in 8 (13,1%) patients who received lithium and 3 patients (4,7%) who received valproate (p=0,12). The most common of them were tremor, nausea, dry mouth. There were no clinically significant abnormalities in laboratory values, vital functions and EEG. In conclusion, the results demonstrated equal therapeutic efficacy, tolerability and safety of valproate and lithium in the treatment of manic episodes in patients with bipolar disorder.

[Comparative efficacy and tolerability of carbamazepine and oxcarbazepine during long therapy of patients with bipolar and schizoaffective disorders].

An aim of the study was to adjust the technique of using oxcarbazepine (OCB) and to study its preventive action and tolerability compared to carbamazepine (CBM) in patients with bipolar and schizoaffective disorders. The study included 48 patients (7 male and 41 female), aged from 18 to 70 years, with phasic psychoses (bipolar disorder, type I - 29 patients and schizoaffective disorder - 19 patients). Patients were randomized into 2 treatment groups: 1 - 28 patients who received CBM in doses 300-1600 mg/day (mean 700+/-120 mg/day) during 25,43+/-2,34 months; 2 - 20 patients who received OCB in doses 600-1800 mg/day (mean 900+/-145 mg/day) during 12+/-0,65 months. Duration of affective symptoms during the preventive therapy with CBM was reduced by 50,1% and that for OCB - by 49,1%; a number of episodes decreased by 34,6 and 35,1%, respectively. A significant effect, i.e. complete stopping of phases, was found in 35,7% of patients of the CBM group and in 40% of patients of the OCB group. The drugs had approximately equal preventive efficacy in regard to depressive and mania phases and episodes of schizoaffective disorders as well. Moreover, both drugs were clearly able to stop the rapid cyclic course of bipolar affective disorder. Side-effects were seen in 67,86% of patients treated with CBM and 55% of patients treated with OCB. Preventive features of OCB were comparable to those of CBM for intensity and spectrum of action. The adjustment of doses for OCB therapy does not need any significant correction, the drug causes less side-effects and subjectively is better tolerated by patients.

Intramuscular olanzapine vs. intramuscular short-acting antipsychotics: safety, tolerability and the switch to oral antipsychotic medication in patients with schizophrenia or acute mania.

BACKGROUND: This study compared the safety, tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular (IM) olanzapine or other IM antipsychotics for the treatment of acute agitation. METHODS: Patients (N = 2011) from 15 countries participated in this prospective, observational, non-interventional study. Inpatients requiring treatment with at least one IM injection of a short-acting antipsychotic were assessed at baseline and within 7 days after the first IM injection. Treatment groups comprised: (i) patients prescribed IM olanzapine at baseline; and (ii) patients prescribed any other IM antipsychotic medication at baseline. Outcome measures included: treatment-emergent adverse events, concomitant psychotropic medication and the time taken to switch to oral medication. RESULTS: Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group (34.4% vs. 46.2%, p < 0.001). The most frequently reported adverse events in both groups were: sedation, Parkinsonism, disturbance in attention, akathisia, dystonia and orthostatic hypotension. Fewer patients in the IM olanzapine group used anticholinergics (13.9% vs. 42.5%, p < 0.001) or anxiolytics/hypnotics (47.6% vs. 51.6%, p = 0.023). Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group (median time = 46.5 vs. 48.0 h, p = 0.009). CONCLUSIONS: These findings suggest that IM olanzapine may have a favourable impact on individual patients. However, the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone.

[A comparative study of efficacy and safety of torin and zoloft].

Zoloft (sertraline) is an original antidepressant of "Pfizer", torin is a generic form of sertraline of Veropharm. An aim of the study was to compare clinical effectiveness and tolerability of original and generic drugs. Forty patients with moderate and severe depression without psychotic symptoms have been studied: 20 of them were treated with torin and 20 with zoloft. Patient's state has been assessed during 7 weeks (1 week--wash out and 6 week--active therapy) clinically and using the Hamilton and CGI scales on 7th, 14th, 21st, 28th and 42nd days. The clinical equivalence of torin and the original drug demonstrated. Torin had a distinct thymoanaleptic effect, the primary action of which addresses anxious affect. This drug was soft as well as zoloft.

Psychiatry in selected countries of Central and Eastern Europe: an overview of the current situation.

OBJECTIVE: To review the current status of psychiatry in selected countries of Central and Eastern Europe: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and Slovenia. METHOD: A group of psychiatrists from the region evaluated the status of psychiatry at the end of 2004 based on data from their countries and information available on WHO homepages. RESULTS: There is a shift from traditional in-patient facilities towards out-patient and community services as evidenced by a decreasing number of hospital beds. Economic pressures affect the financing of psychiatric services, and reimbursement for novel psychotropics. Political changes were followed by updated legislation. Psychiatric training, pre-, postgraduate and continuous medical education, are gradually being transformed. Scientific output as measured by publications in peer-reviewed journals has been significantly lower than in the West. CONCLUSION: The major changes in the period of transition documented in the review pose new challenges for psychiatry.

[Comparative efficacy and tolerability of paroxetine and amitriptiline in long-term therapy preventing depressive recurrences].

An open comparative randomized study of paroxetine (selective inhibitor of serotonin re-uptake) and tricyclic antidepressant amitriptiline has been conducted. These drugs were used for the treatment of 43 patients with recurrent depression (RD) with frequent relapses (ICD-10 F33.0-F33.2) during 12 months. There were 2 groups matched for demographic and clinical data, one included 21 patients treated by paroxetine and the other 22 patients switched to amitriptiline. Basing on clinical records and scores on a number of scales, i.e. HAM-D, CGI, quality of life, high efficacy of the drugs was confirmed, being estimated as 90,5% responders in the paroxetine group and 69,2% in the amitriptiline one, with the marked advantage of the former medication. The better tolerability, possibility of single intake and absence of severe side-effects argue for preferable use of paroxetine during long-term therapy in RD patients with frequent relapses.