Meta-analysis of the effects of anti-migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization.

The main reasons for the low reliability of results from preclinical studies are the lack of prior sample size calculations and poor experimental design. Here, we demonstrate how the tools of meta-analysis can be implemented to tackle these issues. We conducted a systematic search to identify controlled studies testing established migraine treatments in the electrophysiological model of trigeminovascular nociception (EMTVN). Drug effects on the two outcomes, dural stimulation-evoked responses and ongoing neuronal activity were analysed separately using a three-level model with robust variance estimation. According to the meta-analysis, which included 21 experiments in rats reported in 13 studies, these drugs significantly reduced trigeminovascular nociceptive traffic, affecting both outcomes. Based on the estimated effect sizes and outcome variance, we provide guidance on sample sizes allowing to detect such effects with sufficient power in future experiments. Considering the revealed methodological features that potentially influence the results and the main source of statistical bias of the included studies, we discuss the translational potential of the EMTVN and the steps needed to improve it. We believe that the presented approach can be used for design optimization in research with other animal models and as such deserves further validation.

Pilot study of tolerability and safety of opioid receptor antagonists as novel therapies for chronic pain among persons living with HIV with past year heavy drinking: a randomized controlled trial.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03278886.

Proactive coping and spirituality among patients who left or remained in antiretroviral treatment in St Petersburg, Russian Federation.

Positive Psychology, the study of "positive" factors or strengths and evidence-based interventions to increase them, is a rapidly developing field that is beginning to be applied to HIV care. Proactive coping and spirituality are two positive characteristics that have been examined in multiple chronic serious health conditions. In the present study, lost-to-care (LTCs; did not attend treatment for ≥12 months; n = 120) and engaged-in-care HIV clinic patients (EICs; attended treatment for ≥12 months and adherent with antiretrovirals; n = 120) in Leningrad Oblast, Russian Federation were compared on the Proactive Coping Inventory and View of God Scale. EICs had higher scores in proactive coping [t(229) = 3.69; p = .001] and instrumental [t(232) = 2.17; p = .03] and emotional [t(233) = 2.33; p = .02] support, indicating that they engage in autonomous goal setting and self-regulate their thoughts and behaviors; obtain advice and support from their social network; and cope with emotional distress by turning to others. LTCs had higher scores in avoidance coping [t(236) = -2.31; p = .02]. More EICs were spiritual, religious, or both [ χ(2)(1, N = 239) = 7.49, p = .006]. EICs were more likely to believe in God/Higher Power [χ(2)(1, N = 239 = 8.89, p = .002] and an afterlife [ χ(2)(1, N = 236) = 5.11, p = .024]; have a relationship with God/Higher Power [ χ(2)(1, N = 237) = 12.76, p = .000]; and call on God/Higher Power for help, healing, or protection [ χ(2)(1, N = 239) = 9.61]. EICs had more positive [t(238) = 2.78; p = .006] and less negative [t(236) = -2.38; p = .002] views of God. Similar proportions, but slightly more EICs than LTCs were members of a faith community; members of a12-step group; or attended religious or spiritual services, meetings, or activities. More EICs than LTCs engaged in private spiritual or religious activities, such as prayer or meditation [ χ(2)(1, N = 239) = 9.226, p = .002].

Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant.

BACKGROUND: Naltrexone is a µ-opioid receptor antagonist that blocks opioid effects. Craving, depression, anxiety, and anhedonia are common among opioid dependent individuals and concerns have been raised that naltrexone increases them due to blocking endogenous opioids. Here, we present data that address these concerns. OBJECTIVE: Assess the relationship between affective responses and naltrexone treatment. METHODS: Opioid dependent patients (N = 306) were enrolled in a three cell (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month trial comparing extended release implantable naltrexone with oral naltrexone and placebo (oral and implant). Monthly assessments of affective responses used a Visual Analog Scale for opioid craving, the Beck Depression Inventory, Spielberger Anxiety Test, and the Ferguson and Chapman Anhedonia Scales. Between-group outcomes were analyzed using mixed model analysis of variance (Mixed ANOVA) and repeated measures and the Tukey test for those who remained and treatment and did not relapse, and between the last measure before dropout with the same measure for those remaining in treatment. RESULTS: Depression, anxiety, and anhedonia were elevated at baseline but reduced to normal within the first 1-2 months for patients who remained in treatment and did not relapse. Other than a slight increase in two anxiety measures at week two, there were no significant between-group differences prior to treatment dropout. CONCLUSION: These data do not support concerns that naltrexone treatment of opioid dependence increases craving, depression, anxiety or anhedonia.

Depression, substance use, viral load, and CD4+ count among patients who continued or left antiretroviral therapy for HIV in St. Petersburg, Russian Federation.

Antiretroviral therapy (ART) became more widely available in the Russian Federation in 2006 when the Global Fund made a contribution to purchase ART with a mandate to increase numbers of patients receiving it. Funds were distributed to AIDS Centers and selected hospitals, and numbers quickly increased. Though ART is highly effective for adherent patients, dropout has been a problem; thus understanding characteristics of patients who remain on ART vs. those who leave treatment may provide information to facilitate engagement. We retrospectively assessed depression, hopelessness, substance use, viral load, and CD4+ counts of 120 patients who dropped out of ART for ≥12 months (Lost-to-Care, LTCs) and 120 who continued for ≥12 months (Engaged-in-Care, EICs). As expected, LTCs had higher viral loads and depression, lower CD4+ counts, more alcohol, heroin, and injection drug use in the past 30 days. A binary logistic regression with Center for Epidemiologic Studies Depression score, Beck Hopelessness score, whether drugs/alcohol had ever prevented them from taking ART, and past 30 days' alcohol use [χ(2)(4) = 64.27, p = .0.000] correctly classified 74.5% of participants as LTC or EIC, suggesting that integrated treatment for substance use, psychiatric, and HIV could reduce dropout and improve outcomes.

Lost-to-care and engaged-in-care HIV patients in Leningrad Oblast, Russian Federation: barriers and facilitators to medical visit retention.

Sixty-nine percent of the 1.5 million Eastern Europeans and Central Asians with HIV live in the Russian Federation. Antiretroviral therapy (ART) is effective but cannot help those who leave treatment. Focus groups with patients who dropped out of ART for ≥12 months (lost-to-care, LTCs, n = 21) or continued for ≥12 months (engaged-in-care; EICs; n = 24) were conducted in St. Petersburg. Structural barriers included stigma/discrimination and problems with providers and accessing treatment. Individual barriers included employment and caring for dependents, inaccurate beliefs about ART (LTC only), side-effects, substance use (LTCs, present; EICs, past), and depression. Desire to live, social support, and spirituality were facilitators for both; EICs also identified positive thinking and experiences with ART and healthcare/professionals. Interventions to facilitate retention and adherence are discussed.

The association of obesity with eating disorders risk: online survey of a large cohort of Russian-speaking individuals seeking medical weight correction assistance.

BACKGROUND: Eating Disorders pose a serious health risk to individuals. Often, eating disorder symptoms are overlooked when assessing obesity risk. The current cross-sectional study was focused on the search of association between disordered eating behaviors evaluated by Eating Attitudes Test 26 (EAT-26) and obesity in a large cohort of Russian-speaking adults seeking online assistance with medical weight correction. METHODS: The web-based cross-sectional study evaluated the data of online Eating Attitudes Test 26 (EAT-26) completed by 13,341 registered adult visitors of weight loss clinic website. The EAT-26 provides an overall score for potential eating disorders risk, as well as scores for three subscales: Bulimia, dieting, and oral control. Additional self-reported information about sex, weight, height, and age of respondents was used for analysis. The nonparametric analysis of variance and binominal logistic regression modeling were applied to search for an association between obesity and EAT-26 total score and subscales scores. The critical level of the significance was considered as α = 0.05. RESULTS: Women (94%) had lower BMI values but higher EAT-26 total score than men, which was indicated as statistically significant by a Wilcoxon Signed-Ranks Test (Z = - 11.80, p < 0.0001). Logistic regression for the whole cohort revealed that Bulimia subscale score was associated with higher risk of obesity (OR = 1.03, 95% CI 1.02-1.05) whereas higher score of EAT-26 oral control subscale was associated with decreased risk of obesity (OR = 0.93, 95% CI 0.91-0.95). Separate analysis for men and women showed that in men higher obesity risk was associated with higher oral control subscale scores (OR = 1.08, 95% CI 1.06-1.11); while in women both dieting and bulimia subscales scores were associated with higher obesity risk (OR = 1.02, 95% CI 1.01-1.03 and OR = 1.03, 95% CI 1.02-1.05, respectively). Older age was associated with obesity risk for both women and men. CONCLUSIONS: In a large cohort of individuals seeking medical weight correction assistance, the risk of obesity was associated with the higher EAT-26 scores, age, and sex. Moreover, different eating disorder risk profiles were associated with obesity in men and women. Higher oral control subscale score was associated with decreased risk of obesity in women, but with higher risk in men. Older age was a shared obesity risk factor for both sexes. Therefore, the use of EAT-26 would facilitate individual diagnostic assessment for specific eating disorders in different sub-cohorts. Further assessment of separate EAT-26 subscales may be important to predict sex-/age-specific risks of obesity that implies their study in the future. Obesity is a significant health problem. Different factors (e.g. social, biological, and behavioral) are important for their successful treatment. Abnormal eating behaviors may be one of the most likely predictors of increased body weight. This study aims to determine whether there is a significant association between obesity and scores on the eating behavior questionnaire-Eating Attitudes Test-26 (EAT-26)-in a large cohort of adults seeking medical weight correction assistance at a private weight loss clinic web-site. According to the study results, the association was shown for the male sex, older age, and higher Bulimia scores as measured on the EAT-26. Moreover, different EAT-26 scales were associated with obesity risks in women and men subgroups, while older age was a shared risk factor for obesity in both sexes. The findings may suggest sex-/age-specific diagnostic approach and treatment strategies for individuals with obesity.

Differential effects of the Piezo1 agonist Yoda1 in the trigeminovascular system: An electrophysiological and intravital microscopy study in rats.

Migraine is associated with the activation and sensitisation of the trigeminovascular system and is often accompanied by mechanical hyperalgesia and allodynia. The mechanisms of mechanotransduction during a migraine attack are yet unknown. We have proposed that the ion channel Piezo1 may be involved, since it is expressed in endothelial cells as well as in trigeminal ganglion neurons, and thus, may contribute to the activation of both the vascular and neuronal component of the trigeminovascular system. We took advantage of extracellular recordings from the trigeminocervical complex - a key relay centre in the migraine pain pathway, to directly assess the impact of the differently applied Piezo1 agonist Yoda1 on the sensory processing at the spinal level. At a low dose, Yoda1 slightly facilitated the ongoing firing of central trigeminovascular neurons, however, at a high dose, this substance contributed to the suppression of their activity. Using intravital microscopy, we have revealed that Yoda1 at high dose can also induce the dilation of meningeal arteries innervated by trigeminal afferents. Collectively, here we have identified both neuronal and vascular modulation via selective activation of mechanosensitive Piezo1 channels, which provide new evidence in favour of the Piezo1 role in migraine pathogenesis. We propose several mechanisms that may underlie the revealed effects of Yoda1.

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial.

BACKGROUND: Untreated opioid addiction in people with HIV is associated with poor HIV treatment outcomes. Slow-release, long-acting, implantable naltrexone might improve these outcomes. Here, we present results of a study aimed to test this hypothesis. METHODS: We did a 48 week double-blind, double-dummy, placebo-controlled, phase 3, randomised trial with men and women addicted to opioids who were starting antiretroviral therapy (ART) for HIV and whose viral loads were higher than 1000 copies per mL. Participants were seeking treatment at two HIV and two narcology programme centres in Saint Petersburg, Russia, and the surrounding Leningrad region. The Pavlov statistical department created a table with stratification on gender distribution, viral load, and CD4 cell count. We stratified participants according to gender, viral load, and CD4 cells per µL, and randomly assigned (1:1) them to addiction treatment with a naltrexone implant and oral naltrexone placebo (implant group) or oral naltrexone and placebo implant (oral group). The primary outcome was plasma viral load of less than 400 copies per mL at 24 weeks and 48 weeks. We included all randomly assigned participants in outcome analyses (intention to treat). Treatment staff and patients were masked to group assignment. The study is complete and registered at ClinicalTrials.gov, NCT01101815. FINDINGS: Between July 14, 2011, and April 14, 2014, 238 potential participants were recruited and screened, 35 were excluded for not meeting inclusion criteria, three declined to participate, and 200 were randomly assigned to treatment (100 to each group). At week 24, 38 (38) participants in the implant group and 35 (35%) in the oral group had viral loads less than 400 copies per mL (risk ratio 1·1, 95% CI 0·76-1·56; p=0·77). At week 48, 66 participants in the implant group and 50 in the oral group had viral loads less than 400 copies per mL (risk ratio 1·32, 95% CI 1·04-1·68; p=0·045). There were seven serious adverse events: three deaths in the implant group (one due to heart disease, one trauma, and one AIDS), and four in the oral group (two overdoses, one pancreatic cancer, and one AIDS). The overdose deaths occurred 9-10 months after the last naltrexone dose. INTERPRETATION: The longer the blockade of opioid effects, the more protection an individual gets from missed ART doses and impulsive behaviours that lead to relapse and poor, even fatal, outcomes. Commercial development of implants could result in a meaningful addition to addiction treatment options. FUNDING: National Institutes of Health, National Institute on Drug Abuse, Penn Centre for AIDS Research, and Penn Mental Health AIDS Research Centre.

Mitigating risky sexual behaviors among Russian narcology hospital patients: the PREVENT (Partnership to Reduce the Epidemic Via Engagement in Narcology Treatment) randomized controlled trial.

AIM: To assess the effectiveness of a sexual risk reduction intervention in the Russian narcology hospital setting. DESIGN, SETTING AND PARTICIPANTS: This was a randomized controlled trial from October 2004 to December 2005 among patients with alcohol and/or heroin dependence from two narcology hospitals in St Petersburg, Russia. INTERVENTION: Intervention subjects received two personalized sexual behavior counseling sessions plus three telephone booster sessions. Control subjects received usual addiction treatment, which did not include sexual behavior counseling. All received a research assessment and condoms at baseline. MEASUREMENTS: Primary outcomes were percentage of safe sex episodes (number of times condoms were used / by number of sexual episodes) and no unprotected sex (100% condom use or abstinence) during the previous 3 months, assessed at 6 months. FINDINGS: Intervention subjects reported higher median percentage of safe sex episodes (unadjusted median difference 12.7%; P = 0.01; adjusted median difference 23%, P = 0.07); a significant difference was not detected for the outcome no unprotected sex in the past 3 months [unadjusted odds ratio (OR) 1.6, 95% confidence interval (CI) 0.8-3.1; adjusted OR 1.5, 95% CI 0.7-3.3]. CONCLUSIONS: Among Russian substance-dependent individuals, sexual behavior counseling during addiction treatment should be considered as one potential component of efforts to decrease risky sexual behaviors in this HIV at-risk population.

Neurocognitive characterizations of Russian heroin addicts without a significant history of other drug use.

Research on the neurocognitive characteristics of heroin addiction is sparse and studies that do exist include polydrug abusers; thus, they are unable to distinguish neurocognitive effects of heroin from those of other drugs. To identify neurocognitive correlates specific to heroin addiction, the present study was conducted in St. Petersburg, Russia where individuals typically abuse and/or become addicted to only one substance, generally alcohol or heroin. Heroin addicts were recruited from an inpatient treatment facility in St. Petersburg. Three comparison groups included alcoholics, addicts who used both alcohol and heroin, and non-abusers. Psychiatric, background, and drug history evaluations were administered after detoxification to screen for exclusion criteria and characterize the sample. Executive Cognitive Functions (ECF) that largely activate areas of the prefrontal cortex and its circuitry measured include complex visual pattern recognition (Paired Associates Learning), working memory (Delayed Matching to Sample), problem solving (Stockings of Cambridge), executive decision making (Cambridge Decision Making Task), cognitive flexibility (Stroop Color-Word Task) and response shifting (Stop Change Task). In many respects, the heroin addicts were similar to alcohol and alcohol+heroin dependent groups in neurocognitive deficits relative to controls. The primary finding was that heroin addicts exhibited significantly more disadvantageous decision making and longer deliberation times while making risky decisions than the other groups. Because the nature and degree of recovery from drug abuse are likely a function of the type or pattern of neurocognitive impairment, differential drug effects must be considered.

Nonverbal behavior of human addicts: multimetric analysis.

AIMS: Ethological approach followed by multimetric statistical analysis was applied to characterize and discriminate alcohol, heroin and dual, alcohol and heroin, dependent subjects. DESIGN: Heroin, alcohol, and dual dependent patients (n=51) after one month of stabilization of remission and control volunteers (n=34) without a history of significant drug or alcohol use were interviewed and videotaped during the interview by approbation. Nonverbal behavioral cues monitored during the interview were analyzed by means of general linear procedure followed by correlation, factor and discriminant function analyses. FINDINGS: By using this approach the attempt to discriminate addicted groups between each other failed. Therefore we found acceptable to combine subjects in one group and to suggest the similarity between alcohol and heroin dependence. It was found that principal markers of behavioral structure in addicted subjects were higher responsivity to communicate distance, less expression of affiliation behavioral pattern, low level of correlations between different behavioral patterns, and unclear factor structure. Behavioral pattern "affiliation" was identified as discriminate behavior between control and addicted subjects. CONCLUSIONS: Nonverbal cues of human behavior identified clear differences between healthy control and addictive subjects. Therefore, ethological approach described in this paper could be recommended for future use in clinical practice.

Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis.

Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR) sequence. Expanded Disability Status Scale (EDSS) score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54) of patients. LMCE-positive patients had longer disease duration (p = 0,0098) and higher EDSS score (p = 0,039), but not a higher relapse rate (p = 0,091). No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected (p = 0,3842). Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume (p = 0.043, F = 2.529), the total grey matter volume (p = 0.043, F = 2.54), and total ventricular volume (p = 0.039, F = 2.605). Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

Naltrexone with or without fluoxetine for preventing relapse to heroin addiction in St. Petersburg, Russia.

This randomized placebo-controlled trial tested the efficacy of oral naltrexone with or without fluoxetine for preventing relapse to heroin addiction and for reducing HIV risk, psychiatric symptoms, and outcome. All patients received drug counseling with parental or significant-other involvement to encourage adherence. Patients totaling 414 were approached, 343 gave informed consent, and 280 were randomized (mean age, 23.6 +/- 0.4 years). At 6 months, two to three times as many naltrexone patients as naltrexone placebo patients remained in treatment and had not relapsed, odds ratio (OR) = 3.5 (1.96-6.12), p < .0001. Overall, adding fluoxetine did not improve outcomes, OR = 1.35 (0.68-2.66), p = .49; however, women receiving naltrexone and fluoxetine showed a trend toward a statistically significant advantage when compared to women receiving naltrexone and fluoxetine placebo, OR = 2.4 (0.88-6.59), p = .08. HIV risk, psychiatric symptoms, and overall adjustment were markedly improved among all patients who remained on treatment and did not relapse, regardless of group assignment. More widespread use of naltrexone could be an important addition to addiction treatment and HIV prevention in Russia.

Effects of morphine and cocaine in mice with stable high aggressive and nonaggressive behavioral strategy.

The social group experience of mice with opposite aggressive and nonaggressive behavioral strategies was examined to modulate reinforcing effects of morphine and cocaine. Highly aggressive and nonaggressive male mice cohoused for long period in three-member groups were tested to self-administrate the drugs and to develop conditioned place preferring by them. Mouse triads formed by principle of descending aggression were used as a model of linear hierarchical group. The level of mouse aggression was identified previously within the stock group and during encounter with unknown intruder that continued to be stable over the time of experiment. Highly aggressive mice self-administered morphine and cocaine at higher unit concentrations (1.5 and 1.5 mg/ml) as compare with nonaggressive animals (0.5 and 0.25, 0.5, 1.0 mg/ml). Both morphine (2.5, 5.0, 10.0, and 20.0 mg/kg) and cocaine (2.5, 5.0, and 10.0 mg/kg) induced conditioned place preference in nonaggressive mice at all doses. In contrast, morphine had no effect in highly aggressive mice, while cocaine induced place conditioning at the highest doses (10 mg/kg) only. Our results illustrate that social experience in a stable group alter mouse sensitivity to the rewarding properties of drugs of abuse and social state should be taken into account in the experiments when social interactions are present.

Naltrexone for heroin dependence treatment in St. Petersburg, Russia.

Naltrexone may be more effective for treating opioid (heroin) dependence in Russia than in the U.S. because patients are mostly young and living with their parents, who can control medication compliance. In this pilot study we randomized 52 consenting patients who completed detoxification in St. Petersburg to a double blind, 6-month course of biweekly drug counseling and naltrexone, or counseling and placebo naltrexone. Significant differences in retention and relapse favoring naltrexone were seen beginning at 1 month and continuing throughout the study. At the end of 6 months, 12 of the 27 naltrexone patients (44.4%) remained in treatment and had not relapsed as compared to 4 of 25 placebo patients (16%; p<0.05). Since heroin dependence is the main way HIV is being spread in Russia, naltrexone is likely to improve treatment outcome and help reduce the spread of HIV if it can be made more widely available.

Naltrexone with or without guanfacine for preventing relapse to opiate addiction in St.-Petersburg, Russia.

BACKGROUND: Stress is a key precipitant to discontinuing naltrexone and relapsing to opiate abuse. Alpha-2 adrenergic agonists like guanfacine may reduce stress induced craving and have reduced opiate relapse in small clinical trials. METHODS: This randomized, double blind double dummy placebo-controlled 6-month trial tested oral naltrexone with or without guanfacine for reducing stress and preventing opiate relapse. We randomized 301 patients to: naltrexone 50 mg/day+guanfacine 1 mg/day (n=75) (N/G), naltrexone+guanfacine placebo (N/P) (n=76), naltrexone placebo+guanfacine (n=75) (P/G), and double placebo (n=75) (P/P). RESULTS: Among the 75 patients in each group the percentage still retained on naltrexone treatment at six months was: N/G 26.7%, N/P 19.7% (p=0.258 to N/G), P/G 6.7% (p<0.05 to both N groups), and P/P 10.7% (p=0.013 to N+G). Guanfacine reduced the severity of stress particularly at weeks 10 and 18. Adverse events (AE) were infrequent (4.7%) without group differences, with most common AEs: headache, poor appetite, insomnia, and dizziness. CONCLUSIONS: Adding guanfacine to naltrexone did not improve treatment retention or opiate free urines, but it reduced both stress and craving at later time points in treatment, which may be related to stress-induced craving and the animal model of incubation of reinstatement. During treatment, HIV risk, anxiety, and depression reduced among all patients in treatment, regardless of group.

Naltrexone implant for the treatment of polydrug dependence: a randomized controlled trial.

OBJECTIVE: The majority of drug addicts are polydrug dependent, and no effective pharmacological treatment is currently available for them. The authors studied the overall real-world effectiveness of naltrexone implant in this patient population. METHOD: The authors assessed the effectiveness of a naltrexone implant in the treatment of coexisting heroin and amphetamine polydrug dependence in 100 heroin- and amphetamine-dependent outpatients in a 10-week randomized, double-blind, placebo-controlled trial. The main outcome measures were retention in the study, proportion of drug-free urine samples, and improvement score on the Clinical Global Impressions Scale (CGI). Analyses were conducted in an intent-to-treat model. RESULTS: At week 10, the retention rate was 52% for patients who received a naltrexone implant and 28% for those who received a placebo implant; the proportions of drug-free urine samples were 38% and 16%, respectively, for the two groups. On the CGI improvement item, 56% of the patients in the naltrexone group showed much or very much improvement, compared with 14% of those in the placebo group (number needed to treat=3). CONCLUSIONS: Naltrexone implants resulted in higher retention in the study, decreased heroin and amphetamine use, and improved clinical condition for patients, thus providing the first evidence of an effective pharmacological treatment for this type of polydrug dependence.

Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence.

CONTEXT Sustained-release naltrexone implants may improve outcomes of nonagonist treatment of opioid addiction. OBJECTIVE To compare outcomes of naltrexone implants, oral naltrexone hydrochloride, and nonmedication treatment. DESIGN Six-month double-blind, double-dummy, randomized trial. SETTING Addiction treatment programs in St Petersburg, Russia. PARTICIPANTS Three hundred six opioid-addicted patients recently undergoing detoxification. INTERVENTIONS Biweekly counseling and 1 of the following 3 treatments for 24 weeks: (1) 1000-mg naltrexone implant and oral placebo (NI+OP group; 102 patients); (2) placebo implant and 50-mg oral naltrexone hydrochloride (PI+ON group; 102 patients); or (3) placebo implant and oral placebo (PI+OP group; 102 patients). MAIN OUTCOME MEASURE Percentage of patients retained in treatment without relapse. RESULTS By month 6, 54 of 102 patients in the NI+OP group (52.9%) remained in treatment without relapse compared with 16 of 102 patients in the PI+ON group (15.7%) (survival analysis, log-rank test, P < .001) and 11 of 102 patients in the PI+OP group (10.8%) (P < .001). The PI+ON vs PI+OP comparison showed a nonsignificant trend favoring the PI+ON group (P = .07). Counting missing test results as positive, the proportion of urine screening tests yielding negative results for opiates was 63.6% (95% CI, 60%-66%) for the NI+OP group; 42.7% (40%-45%) for the PI+ON group; and 34.1% (32%-37%) for the PI+OP group (P < .001, Fisher exact test, compared with the NI+OP group). Twelve wound infections occurred among 244 implantations (4.9%) in the NI+OP group, 2 among 181 (1.1%) in the PI+ON group, and 1 among 148 (0.7%) in the PI+OP group (P = .02). All events were in the first 2 weeks after implantation and resolved with antibiotic therapy. Four local-site reactions (redness and swelling) occurred in the second month after implantation in the NI+OP group (P = .12), and all resolved with antiallergy medication treatment. Other nonlocal-site adverse effects were reported in 8 of 886 visits (0.9%) in the NI+OP group, 4 of 522 visits (0.8%) in the PI+ON group, and 3 of 394 visits (0.8%) in the PI+ON group; all resolved and none were serious. No evidence of increased deaths from overdose after naltrexone treatment ended was found. CONCLUSIONS The implant is more effective than oral naltrexone or placebo. More patients in the NI+OP than in the other groups develop wound infections or local irritation, but none are serious and all resolve with treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00678418.

Gender differences in neurocognitive functioning among alcohol-dependent Russian patients.

BACKGROUND: There are a limited number of studies that have examined gender differences in the neurocognitive test performances of alcohol-dependent individuals. Those that have been conducted reported that compared with men, women's visuospatial skills, psychomotor speed, and working memory are more profoundly affected by chronic alcohol abuse despite a shorter duration of drinking and a lesser quantity of alcohol consumed. METHODS: The performances of Russian male and female alcoholic and nonalcoholic control subjects were compared on a series of neurocognitive tasks that assess motor speed, visuoperceptual processing, visuospatial processing, decision making, and cognitive flexibility. RESULTS: Group and gender differences emerged on specific components of each task administered. Female compared with male alcoholic subjects exhibited poorer performances on tests of visual working memory, spatial planning and problem solving, and cognitive flexibility. CONCLUSION: The data support and extend prior research demonstrating a more deleterious impact of alcohol dependence on female alcoholic subjects' cognitive functioning compared with male alcoholic subjects. Several theories are offered to account for gender differences in neurocognitive performance.