The effects of extended-release naltrexone on holiday drinking in alcohol-dependent patients.
ABSTRACT A post hoc analysis examined the effect of extended-release naltrexone (XR-NTX) treatment combined with psychosocial support on alcohol consumption during holiday and nonholiday periods in a cohort of alcohol-dependent patients who had maintained at least 4 days of continuous abstinence before receiving their first treatment. Three parameters of drinking behavior were examined: percentage of drinking days, percentage of heavy drinking days, and the number of drinks per day. Patients receiving XR-NTX 380 mg reported significantly lower median percentages of drinking days, heavy drinking days, and the number of drinks per day compared with the placebo group. Patients treated with XR-NTX 190 mg reported similar results overall. The results suggest that treatment with XR-NTX 380 mg in combination with psychosocial intervention leads to significant reductions in alcohol consumption, with some measures indicating abstinence in alcohol-dependent patients with initial abstinence during holiday periods.
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ABSTRACT: Context Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited.Objective To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients.Design, Setting, and Participants A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection.Intervention An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention.Main Outcome Measure The event rate of heavy drinking days in the intent-to-treat population.Results Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .03) and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups.Conclusions Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence. Figures in this Article Alcohol dependence is a major public health problem, which worldwide is the fourth leading cause of disability.1 Alcohol dependence is present in approximately 4% of the US adult population,2 is common among primary care patients,3- 4 and may contribute to more than 100 000 preventable deaths per year.5 Addiction counseling, behavioral treatments, and self-help groups (eg, Alcoholics Anonymous) are the primary interventions used to treat alcohol dependence in the United States. Although these treatments are often effective, a substantial number of patients fail to complete them or relapse.6 Similar to diabetes, hypertension, and asthma, alcohol dependence is increasingly recognized as a chronic disease in which genetic vulnerability and social and environmental factors are involved in the etiology and course of the disease.7 As with other chronic diseases, long-term comprehensive management strategies are necessary to achieve and sustain the benefits of alcohol dependence treatment. Pharmacotherapy represents an emerging treatment option that could be used by primary care practitioners and addiction specialists.8 In 1994, naltrexone was approved by the US Food and Drug Administration to treat alcohol dependence after the medication was shown to reduce drinking frequency and the likelihood of relapse to heavy drinking.9- 10 Naltrexone, an opioid antagonist, is thought to reduce the reinforcing subjective or behavioral response to alcohol.11- 12 In about 3200 alcohol-dependent patients in at least 19 published controlled studies, oral naltrexone, compared with placebo, has shown efficacy in the treatment of alcohol dependence although some studies have reported no or minimal effectiveness.13- 18 Despite substantial evidence of efficacy, clinical use of naltrexone has been limited, in part because of the heterogeneity in treatment response.19 One documented reason for the heterogeneity of response across naltrexone trials has been poor adherence to the daily medication regimen.20- 23 Adherence to a daily oral medication regimen is a general problem in medicine.7 Additional challenges to adherence in the context of substance abuse include variable patient motivation toward treatment; impaired cognitive function, particularly executive function; and denial.24 As a prototypical addictive disorder, alcohol dependence is thought to involve dysfunction of the brain’s reward system with attendant impaired control over drives and motivation.25 Moreover, treatment may directly conflict with the behaviors and rewards associated with the abused substance.26 Since the 1970s, several efforts have been made to develop a parenteral extended-release naltrexone,27- 29 and 1 formulation has reported an effect on abstinence.29 Recently, a new polylactide-co-glycolide (PLG)–based, long-acting naltrexone formulation that releases naltrexone for 1 month following a single injection was developed.30 We conducted a 6-month, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 dosing levels of this long-acting injectable formulation of naltrexone in combination with a low-intensity psychosocial intervention for treatment of alcohol dependence.JAMA The Journal of the American Medical Association 293(13):1617-1625. · 29.98 Impact Factor
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ABSTRACT: Ninety-seven alcohol-dependent patients were treated for 12 weeks in a double-blind, placebo-controlled study evaluating naltrexone and two manual guided psychotherapies in the treatment of alcohol dependence. Patients were randomized to receive either naltrexone or placebo and either coping skills/relapse prevention therapy or a supportive therapy designed to support the patient's own efforts at abstinence without teaching specific coping skills. Naltrexone proved superior to placebo in measures of drinking and alcohol-related problems, including abstention rates, number of drinking days, relapse, and severity of alcohol-related problems. Medication interacted with the type of psychotherapy received. The cumulative rate of abstinence was highest for patients treated with naltrexone and supportive therapy. For those patients who initiated drinking, however, patients who received naltrexone and coping skills therapy were the least likely to relapse.Archives of General Psychiatry 12/1992; 49(11):881-7. · 13.77 Impact Factor
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ABSTRACT: To summarize fatal motor vehicle crash deaths in the United States by time of day, day of week, month, and season, and to determine why some days of the year tend to experience a relatively high number of deaths.Method: Crash deaths were identified and categorized using the Fatality Analysis Reporting System. Days of the year with relatively high crash deaths were compared to the two days that occurred exactly one week before and one week after. On average, motor vehicle crashes in the United States result in more than 100 deaths per day, but there is much day-to-day variability. During 1986-2002 the single day fatality count ranged from a low of 45 to a high of 252. Summer and fall months experience more crash deaths than winter and spring, largely due to increased vehicle travel. July 4 (Independence Day) has more crash deaths on average than any other day of the year, with a relatively high number of deaths involving alcohol. January 1 (New Year's Day) has more pedestrian crash deaths on average, plus it has the fifth largest number of deaths per day overall, also due to alcohol impairment. On other days the high numbers of deaths are likely due to increases in holiday or recreational travel. Every day of the year results in many crash deaths, but certain days stand out as particularly risky. The temporal and geographic spread of crash deaths, as well as the view of driving as a routine task, inures the public to this continuing problem. Innovative strategies are needed both to raise awareness and to work toward a solution.Injury Prevention 03/2005; 11(1):18-23. · 1.76 Impact Factor