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.

Effect of memantine on cue-induced alcohol craving in recovering alcohol-dependent patients.

OBJECTIVE: Ethanol blocks N-methyl-d-aspartic acid (NMDA) glutamate receptors. Increased NMDA receptor function may contribute to motivational disturbances that contribute to alcoholism. The authors assessed whether the NMDA receptor antagonist memantine reduces cue-induced alcohol craving and produces ethanol-like subjective effects. METHOD: Thirty-eight alcohol-dependent inpatients participated in three daylong testing sessions in a randomized order under double-blind conditions. On each test day, subjects received 20 mg of memantine, 40 mg of memantine, or placebo, and subjective responses to treatment were assessed. The level of alcohol craving was assessed before and after exposure to an alcohol cue. RESULTS: Memantine did not stimulate alcohol craving before exposure to an alcohol cue, and it attenuated alcohol cue-induced craving in a dose-related fashion. It produced dose-related ethanol-like effects without adverse cognitive or behavioral effects. CONCLUSIONS: These data support further exploration of whether well-tolerated NMDA receptor antagonists might have a role in the treatment of alcoholism.

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.

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.

Alcohol use in pregnant and nonpregnant Russian women.

BACKGROUND: Alcohol consumption in Russia is reportedly high for both men and women; most studies of Russian drinking have used questionnaires not designed specifically to measure alcohol consumption or to interview women. This study was designed specifically to measure drinking patterns among pregnant and nonpregnant Russian women. METHODS: Eight hundred ninety-nine women of child-bearing age in St. Petersburg, Russia, were interviewed in employment centers, educational centers, and at obstetric and gynecologic (OB/GYN) clinics and hospitals. Measurement of drinking used several types of drinking questions and time frames. RESULTS: Nearly all nonpregnant Russian women (95.9%) reported consuming alcohol in the last 12 months. Among nonpregnant women drinkers, 7.6% reported drinking heavily (29.58 mL or more ethanol/d), and 18.4% reported drinking >or=5 on at least 1 occasion. Contrary to expectations of Russian obstetricians, pregnant Russian women readily answered detailed questions about their drinking behavior during pregnancy. Nearly all pregnant women drank in the year before they became pregnant; of these, 60.0% reported drinking when they knew they were pregnant, and 34.9% drank in the past 30 days. Among pregnant women who drank in the past 30 days, 7.4% reporting having >or=5 drinks on at least 1 occasion. Nevertheless, more than 90% of pregnant and nonpregnant Russian women believed that alcohol has a detrimental effect on pregnancy outcomes. CONCLUSIONS: Pregnant and nonpregnant Russian women were willing to answer detailed questions about their drinking behavior. Although most pregnant women studied reduced their drinking during pregnancy, one-third of the pregnant women did not stop drinking. It is important to find out what enabled two-thirds of the pregnant women to stop drinking before or during their pregnancy.

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.