An open-label study of a functional opioid kappa antagonist in the treatment of opioid dependence.

Several lines of evidence, including the well-established observation that kappa opiate agonists produce dysphoria and psychotomimetic effects in humans, suggest that dysfunction of the endogenous kappa opioid system may contribute to opioid and cocaine addiction. The objective of this open-label study was to determine the effectiveness of a functional kappa antagonist as a treatment for opioid dependence. This was accomplished by combining a partial mu agonist/kappa antagonist (buprenorphine, 4 mg, sublingual) with a mu antagonist (naltrexone, 50 mg by mouth), theoretically leaving kappa antagonism as the major medication effect. Subjects were treatment-seeking heroin-dependent (as per Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) men (41 +/- 7 years old; 19 +/- 8 years heroin use) eligible for methadone maintenance. After inpatient detoxification and a naloxone-challenge test to verify that they were not physically dependent on opioids, subjects received naltrexone. Starting on the fourth day, patients also received liquid buprenorphine. All patients received medication at the clinic 6 days per week and a full program of psychosocial treatment. The major endpoints of the study were: pupil diameter to determine if the mu agonist effects of buprenorphine were blocked by naltrexone, urine toxicology, and retention in treatment. Five patients (33%) completed the 3-month study. Four were abstinent from opioids and cocaine for the entire study, and one was abstinent from opioids and cocaine for the last 9 weeks. Six subjects dropped out due to either minor side effects or disliking the sensation of sublingual buprenorphine. There were no significant changes in pupillary diameter. The positive response to treatment exceeds that expected from naltrexone alone (90% dropout). These promising results suggest that controlled studies of this medication combination should be conducted.

Early versus late onset of alcoholism in the elderly.

The age of onset of alcohol-related problems is a typology that is gaining prominence among clinicians. Findings from epidemiological studies suggest that there are a significant number of older alcoholics who first begin to drink alcohol "abusively" in their later years. While few demographic differences appear between late onset and early onset alcoholics, a number of studies have reported clinical differences between these groups that may affect the natural course and treatment outcome of the illness.

Alcoholism in older persons: a review of the literature.

Alcohol abuse and dependence in elderly persons is of growing social concern. The most consistent findings of cross-sectional and longitudinal studies are that the quantity and frequency of alcohol consumption is higher in elderly men than in elderly women, as is the prevalence of alcohol-related problems. Most studies show a decrease with age in consumption and alcohol-related problems among heavy drinkers. Longitudinal studies show no changes in consumption among light drinkers. Elderly persons with lower incomes consume less alcohol than those with higher incomes. Hospitalized and outpatient populations have more problem drinkers, and the elderly alcoholic is at greater risk for medical and psychiatric comorbidity. About one-third to one-half of elderly alcoholics experience the onset of problem drinking in middle or late life. Outcomes seem to be better for those who have late-onset drinking and may be improved for those treated in same-age rather than mixed-age groups.

Tolerability of naltrexone in treating older, alcohol-dependent patients.

The authors conducted an interim analysis of the tolerability of naltrexone among older, alcohol-dependent adults. Thirty-six subjects over 50 years old were enrolled in a 12-week, double blind, placebo-controlled efficacy study of naltrexone. Sixteen subjects received naltrexone and were compared with the placebo group for the development of adverse effects. Self-reported adverse effects did not differ in frequency or duration between the placebo and naltrexone groups. There were no significant differences in laboratory values between the two groups. Naltrexone was well tolerated with no clinically significant adverse effects. However, the efficacy of naltrexone has yet to be determined in this age group.

Naltrexone as an adjunctive treatment for older patients with alcohol dependence.

The authors examined the efficacy of naltrexone as an adjunctive treatment for alcohol dependence in older adults. Forty-four veterans over 50 years of age were enrolled in a 12-week, double-blind, placebo-controlled efficacy study of naltrexone (the equivalent of 50 mg per day). There were no differences in the frequency of any self-reported adverse effects or in liver enzyme values between the placebo- and naltrexone-treated groups. There were no differences between the treatment groups in the number of subjects remaining abstinent or in the number of subjects who relapsed. However, all placebo-treated subjects relapsed after sampling alcohol, whereas only three of six naltrexone-treated subjects met relapse criteria after alcohol exposure (P = 0.024). The authors conclude that naltrexone was well tolerated and efficacious in preventing relapse in subjects who drank.