[Pharmacotherapy in heroin addiction: pharmacological approaches to remission stabilization and recurrence prevention]. / Farmakoterapiia geroinovoi narkomanii: farmakologicheskii podkhod k stabilizatsii remissii i profilaktike retsidivov.

After withdrawal arrest in many heroin addicts, they displayed the syndrome of anhedonia including affective disorders (depression, dysphoria, anxiety), dyssomnia and a pathologic craving for opiates. Anhedonia is often the cause for recurrence in heroine addiction, therefore, an appropriate treatment is an important aspect in recurrence prevention and remission stabilization. Since depression and drive for heroin are the key symptoms in anhedonia, we undertook the efficiency study of therapy (in anhedonia) by antidepressants belonging to the selective serotonin reuptake inhibitors (SSRI) and NMDA receptor antagonists, citalopram and memantine, respectively, which have a clinical antidepressant action and an experimental anti-addictive action. Both drugs were found to arrest effectively virtually all signs of anhedonia, however, their action on remission stabilization was rather moderate. It looked to be more promising to use, in remission stabilization, the uttermost antagonist of opiate receptors (naltrexone) blocking reliably all heroine effects. A double blind placebo-controlled study, undertaken by us, convincingly showed a significantly smaller number of relapses with naltrexone in heroin addicts. At the same time, the drug had no valuable effect on the anhedonia symptoms, which worsened the compliance entailing a poorer therapy efficiency. Finally, a combination of naltrexone (blocking the heroin action and reducing the recurrence rate) with SSRI antidepressants (effectively arresting the anhedonia symptoms and improving the compliance with naltrexone medication and remission quality) is a most promising approach to remission stabilization and recurrence prevention.

[The relation of psychological characteristics of alcoholics and indices of discrete omega measurement]. / Sviaz' mezhdu psikhologicheskimi kharakteristikami bol'nykh alkogolizmom i pokazateliami diskretnoi omegametrii.

As a result of factor analysis of discrete omega measurement data and psychological studies of 62 chronic alcoholic patients the interconnection was found between one of super-slow physiological process in the brain--omega potential and individual-typological characteristics of personality according to the tests of Spilberger-Khanin, Rosenzweig and MMPI. The obtained results allow to consider the methods of discrete omega measurement with psychoemotional load in the form of imitation of alcohol usage as an objective means of express-test of alcoholic patients psychological state.

[Treatment of alcoholism by affective counterattribution]. / Lechenie alkogolizma s pomoshch'iu affektivnoi kontratributsii.

A new narcopsychotherapeutic technique termed "affective counterattribution" (ACA) is offered to treat alcohol addiction. The use of ACA increased the effectiveness of alcoholism treatment that was ensured by association of strong pharmacogenic negative emotional experience coupled with bright hallucinatory images to notions of alcohol and alcohol-related stimuli. Alcoholic attitude was destroyed and the patients' pathological personality traits were corrected.

[One of the methods of treatment of affective disorders in patients with alcoholism]. / Ob odnom iz metodov lecheniia affektivnykh narushenii u bol'nykh alkogolizmom.

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

[Study of gamma-aminobutyric acid (GABA) concentration in blood plasma of alcoholism patients]. / Issledovanie kontsentratsii gamma-aminomaslianoi kisloty (GAMK) v plazme bol'nykh alkogolizmom.

Concentration of gamma-aminobutyric acid (GABA) was estimated in the plasma of 104 patients with alcoholism during 2 month treatment course in addiction hospital and in 29 healthy volunteers. Highly distinct differences in content of GABA were detected in the plasma of the volunteers and patients with alcoholism, which remained within 60 days of alcohol withdrawal.

[Ethanol inhibits platelet monoamine oxidase type B activity in patients with alcoholism]. / Ingibiruiushchee deistvie étanola na aktivnost' monoaminoksidazy tipaB trombitsitov u bol'nykh alkogolizmom.

The influence of 400 mM ethanol on the activity of monoamine oxidase type B (MAO-B) of blood platelets has been studied in vitro in 30 alcoholic patients and 30 healthy volunteers. Benzylamine was used as a substrate for MAO-B. MAO-B inhibition by ethanol was higher in alcoholics compared to healthy volunteers. The higher vulnerability of MAO-B of alcoholics inhibiting action to of ethanol may be one of the mechanisms underlying some symptoms of alcoholism.

[Dynamics of activity of creatine kinase and its isoenzymes in the serum of patients with alcoholism]. / Dinamika aktivnosti kreatinkinazy i ee izofermentov v syvorotke krovi bol'nykh alkogolizmom.

Activity of creatine kinase (CK) and its isoenzymes was studied in blood serum of 32 patients with alcohol abstinent syndrome of various severity as well as in persons with long-term remission (from 1 to 14 years) as compared with the enzymatic activity in healthy volunteers. The severity of alcohol abstinent syndrome correlated with an increase in the total enzyme activity in blood, where content of the all three CK isoenzymes (MM, MB and BB), especially of BB-CK, was elevated. Content of MB and BB isozymes was increased in blood of patients with long-term remission, while activity of each of the isozyme constituted up to 20-30% of total CK activity, which was by one decimal order higher as compared with control values. Importance of the alterations observed in activity of creatine kinase and its isoenzymes for diagnosis of alcoholism, especially under conditions of alcohol abuse and long-term alcohol abstinence, is discussed.

[Injectable extended-release naltrexone for the prevention of relapse to opioid dependence following opioid detoxification]. / Primenenie prolongirovannogo in''ektsionnogo naltreksona dlia profilaktiki retsidiva opioidnoi zavisimosti posle detoksikatsii.

Opioid dependence is a growing, worldwide public health concern. In contrast to opioid ?-agonist (or 'substitution') maintenance treatments, injectable extendedrelease naltrexone (XR-NTX), approved in the USA and Russia, is an opioid antagonist, formulated to address nonadherence, which limits the utility of oral naltrexone for opioid dependence. This article reviews the clinical trial data underlying the approval of XR-NTX for opioid dependence and the agent's clinical use. XR-NTX met all primary and secondary end points in a multicenter, placebo-controlled trial (n=250) conducted in Russia, with two discontinuations in each group because of adverse events. Cost-effectiveness analysis of claims data found that 6-month total healthcare costs following XR-NTX (US$8582 per patient) were not significantly different from oral naltrexone (US$8903; p=0.867) or buprenorphine (US$10,049; p=0.414), and were 49% lower than with methadone (US$16,752; p<0.0001). Future research should address induction and duration of treatment with XR-NTX.

[Scientifically decorated approaches in the Russian addiction psychiatry: some thoughts about M.L. Zobin's paper "Placebo technologies in the treatment of substance abuse"]. / Naukoobrazno dekorirovannye podkhody k terapii v rossiiskoi narkologii: razmyshleniia po povodu stat'i M.L. Zobina "Platsebo-tekhnologii v terapii khimicheskikh addiktsii"

Brief intensive behavioral interventions which promise a one session miracle cure from drug or alcohol dependence are very common in the Russian addiction psychiatry, particularly in its commercial domain. Unlike traditional shamanism these behavioral interventions are presented to the patients as the most recent advances in the main stream addiction medicine and therefore they can be called "scientifically decorated shamanism". The paper includes classification of these methods, reasons for this phenomenon to be so common in the Russian addiction psychiatry (narcology), and also possible approaches to the modernization of the Russian narcology system with evidence based approach to research and clinical practice to be the major one.

[Naltrexone implant treatment of polydrug dependence]. / Primenenie implanta naltreksona dlia terapii polinarkomanii.

Objective. Recent studies indicate that naltrexone implant may be one of the effective pharmacological treatments for opiate dependence. However, nowadays many of addicts are polydrug dependent. The aim of the study was to evaluate the effectiveness of naltrexone implant in the treatment of opiate and amphetamine polydrug dependence. Material and methods. A 10-week randomized, double-blind, placebo-controlled trial with 100 patients dependent on opiates and amphetamines has been conducted. Subjects were randomized in 1:1 ratio to either naltrexone implant or identically looking placebo formulation group. Primary outcome measures were retention in the study, proportion of drug-free urine samples and improvement in the Clinical Global Impression (CGI) scale. Results. At week 10, the retention was 52% among patients with naltrexone vs. 28% among patients with placebo implant (p=0.01), and the proportion of drug-free urine samples was 38% vs. 16% (p=0.01), respectively. Fifty-six per cent of patients treated with naltrexone implant showed marked improvement on CGI compared with 14% of patients treated with placebo (p<0.001, NNT=3.95%, CI 2-4). Conclusion. Naltrexone implant administration resulted in higher retention in the treatment, decreased heroin and amphetamine use, and improved clinical condition of patients, providing the first evidence on effective pharmacological treatment of this kind of polydrug dependence.

[Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomized trial].

UNLABELLED: We aimed to assess the efficacy and safety of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. Two hundreds and fifty patients with opioid dependence were enrolled into the double-blind, placebo-controlled, randomized, 24-week trial. Patients aged 18 years or over who had inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX (n=124) or placebo (n=126). Participants also received 12 biweekly counseling sessions. The primary endpoint was the response profile for confirmed abstinence during weeks 5-24 assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid- free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. IN CONCLUSION: XR-NTX represents a new treatment option. XR-NTX in conjunction with psychosocial treatment was more effective for treatment of opioid dependence compare to psychosocial support and placebo.

[Epidemiology, medical and social features of the addiction to beer and strong alcogol].

The comparative study of the addiction to beer and hard liquor was carried out. Despite of the dramatic increase in the beer consumption in the Russian Federation between 1999 and 2009, the incidence and prevalence of alcohol dependence and alcohol psychoses had decreased. The analysis of preference in alcohol consumption revealed that 90.7% of study participants consumed different types of alcohol beverages: beer and hard liquor. Alcohol addiction caused by the consumption of beer or spirits and wine alone was 1.2% and 8.1%, respectively. Our study of case histories demonstrated that alcohol addiction related predominantly to the beer use was associated with the consumption of smaller doses of pure ethanol, less pronounced abstinent syndrome, less frequent complications, such as the convulsive syndrome and alcoholic psychosis, compared to the addiction to hard liquor. The examination of 106 outpatients with alcohol addiction revealed that patients who preferred hard liquor during the last month consumed more alcohol in terms of pure ethanol. Also, the period of hard drinking was longer and patients had more social, legal, and psychological problems as well as somatic and psychopathological disorders. The higher was the consumption of hard liquor, the severe was the course of alcohol addiction. The least number of biopsychosocial problems was noted in patients who consumed only beer.

[The use of different forms of naltrexone in the treatment of opioid dependence].

The authors compared the results of own studies and foreign publications on the use of different formulations of naltrexone (peroral, implantable, injectable) for the remission stabilization and relapse prevention in patients with opioid dependence. Opioid antagonists, in particular naltrexone, are the unique medication for the specific pharmacotherapy of opioid dependence currently approved in the Russian Federation. The main problem that considerably reduces the efficacy and restricts the use of naltrexone in the treatment of opioid dependence is the problem of compliance. Nevertheless, in the double blind randomized placebo-controlled trials, we have demonstrated the higher efficacy of peroral naltrexone for the remission stabilization compared to analogous foreign publications. It might be explained by the cultural specifics of the family in the Russia Federation, in particular, by the possibility to control the treatment by relatives of the patient. However the possibilities of this control are significantly reduced as the patient gets older. Long-acting depot formulations of naltrexone (implantable and injectable) are more effective than peroral ones that allows to solve the problem of compliance and opens new perspectives in the treatment of opiate dependence.

[The questionnaire "alcohol anosognosia" is a new tool for assessment of anosognosia in patients with alcohol dependence].

The aim of this study was to develop and validate a patient-rated questionnaire for the complex express-assessment of alcohol anosognosia. The questionnaire was tested in 106 inpatients diagnosed with alcohol dependence (ICD-10, item F10.2). The age of the study participants (M+/-SD) was 42.1+/-8.8 years, duration of alcohol dependence 11.3+/-7.0 years. The questionnaire consisted of 7 subscales: Not being in the know, Non-recognition of disease symptoms, Non-recognition of disease in whole, Non-recognition of disease consequences, Emotional rejection of disease, Disagreement with treatment, Non-acceptance of temperance. Psychometric characteristics (external-criterion validity, test-retest validity, internal consistency) were studied and the standardization of the questionnaire was performed. Mean empiric values of subscales were determined. The questionnaire allows to get the complex assessment of anosognosia level by separate components and to present the profile of alcohol anosognosia as well.

[The comparative analysis of high-risk behaviour related to HIV infection in users of psychoactive drugs with stimulating action and opioids].

To study clinical and psychological characteristics associated with high-risk behaviour related to HIV infection in 2006-2007 years, we examined 68 patients with psychoactive drugs (with stimulating action) and opioids (heroin) dependencies. Patients were stratified into 2 groups: users of psychoactive drugs (UPS)--34 patients and opioid users (OU)--34. Behavior of UPS differed from that of OU by using more drug injections per day although the former used syringes of other users less often. Therefore, the risk of being infected was lower in the UPS group compared to the OU group. The evaluation of the risk through sexual transmission did not reveal significant between-group differences.

[The study of characteristics of overdose among users of opioid drug injections].

Overdose is a serious problem as for people addicted to opioid drug injections (ODI) as well as for the community in general. To study characteristics of overdose, authors examined 60 ODI users and analyzed 27 overdose death cases. It has been shown that overdose is rather common among ODI users. Fatal and nonfatal overdoses most frequently take place among men at home or in the street. People often did not receive sufficient help in the overdose situation. We confirm the role of alcohol, long abstinence and variability in drug quality in the development of overdose. Witnesses of overdose in other users reported more health problems, family and social relations, were more concerned with their own and others risk in future compared to those reporting no overdose. Additional predictors were determined: a higher number of overdoses in the past; disturbances of family relations and somatic disorders. Mental disorders predicted the opioid overdose risk among ODI users. ODI users are interested in counseling and training to prevent overdose. Family psychotherapy and early diagnosis of comorbid disorders may be important ways of overdose prevention.

[Naltrexone and fluoxetine for maintenance of remission in patients with heroin addiction: a double-blind randomized placebo-controlled trial].

Two hundreds and eighty patients with heroin addiction were randomized into 4 equal groups. Patients of the group 1 received naltrexone (N) in dosage 50 mg/day and fluoxetine (F) in dosage 20 mg/day during 6 months. Group 2 received N/F-placebo (FN), group 3--N-placebo (NP)/F and group 4--NP/FP. All patients underwent a session of individual psychotherapy for the maintenance of remission. Express urine drugs tests were used for remission control. Compliance was controlled by a riboflavin marker. Clinical state, psychiatric status and social functioning were assessed using quantified international scales and tests. To the end of the 6 month course, 43% of patients of group 1, 36% of group 2, 21% of group 3 and 10% of group 4 were in remission. Therefore, N/F was more effective than F/NP (p < 0.01) and FP/NP (p < 0.001); N/FP was more effective than F/NP (p < 0.05) and NP/FP (p < 0.001); F/NP did not differ significantly from NP/FP (p = 0.1); N/F did not differ from N/FP (p = 0.2). However N/F was more effective compared to N/FP only in women, probably, due to the higher baseline levels of depression, anxiety and anhedonia. Naltrexone was superior to placebo and fluoxetine in the efficacy of maintenance of remission and preventing relapse in patients with heroin addiction. The combination of naltrexone and fluoxetine was more effective compared to the monotherapy with naltrexone in women only.