Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse.
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PMID:Naltrexone in the treatment of alcohol dependence. 816 Dec 96

To test the hypothesis that reduced food intake produced by opioid blockade is due to a reduction in the pleasant aspects of tastes, 18 fasted male college students rated the intensity and pleasantness of soup that contained various concentrations of NaCl and of Kool-Aid that contained various concentrations of sucrose at hourly intervals after ingesting either naltrexone (50 mg) or a placebo in a double-blind study. Hunger, fullness, nausea, and current mood state were also assessed. Lunch followed and food intake was recorded. After placebo, the pleasantness of the salted soup increased as lunchtime approached. After naltrexone, however, soup pleasantness remained unchanged across time. Similar changes were obtained for perceived sweetness and pleasantness of Kool-Aid and for the perceived saltiness of soup. Naltrexone also blocked the increases in hunger ratings that occurred across time in the placebo condition. Nausea was higher after naltrexone. After naltrexone, subjects consumed approximately 500 kcal less at lunch than after placebo. Analysis of covariance suggested that decreased hunger (but not nausea or taste pleasantness) accounted for the naltrexone-induced reduction of food intake.
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PMID:Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans. 185 56

Naltrexone is an important new pharmacologic adjunct to the treatment of heroin dependence. The development of naltrexone has been nurtured in the mature recognition that simple detoxification or simple opiate replacement therapy is not appropriate for every heroin addict. Our current data indicate that naltrexone is safe and effective. Its use may be limited to a minority of addicts, those who are highly motivated and opiate free, because patient compliance has been a major problem with which clinicians using naltrexone have had to contend. Patient compliance is a problem, because there are no immediate consequences to the patient for stopping his naltrexone regimen. Side effects from naltrexone have been minimal and have occurred in a minority of patients. They consist primarily of gastrointestinal symptoms, including nausea and occasionally abdominal pain.
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PMID:Treatment of heroin-dependent persons with antagonists: current status. 679 Oct

When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol and other minor metabolites. Naltrexone has been recently approved by the Food and Drug Administration for the treatment of alcohol dependence. An important clinical issue with naltrexone treatment is predicting patient compliance, which may be influenced by adverse side effects experienced during the medication. We investigated whether subjective side effects were related to urinary concentrations of naltrexone and its metabolite 6 beta-naltrexol 3 hr after administration of 50 mg po naltrexone in 24 male moderate-to-heavy social drinkers. The results showed significantly higher levels of urinary 6 beta-naltrexol (p < 0.05) in those subjects who experienced one or more side effect (i.e., headache, nausea, anxiety, or erection). Urinary naltrexone levels did not differ between the groups. Results also showed an approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant positive correlation between the parent compound and metabolite, suggesting parallel renal clearance. The results of this study suggest a possible mechanism for the side effects observed after acute administration of naltrexone.
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PMID:Naltrexone biotransformation and incidence of subjective side effects: a preliminary study. 926 42

Naltrexone is a pure opioid antagonist that is an effective nonaversive pharmacologic treatment for alcohol dependence. The usual dosage is 50 mg per day. Side effects may include nausea, headache, dizziness and arthralgia. Naltrexone appears to exert its effect by decreasing the craving for alcohol. It has also been useful in allowing some patients to decrease their need for other medications, such as benzodiazepines and antihypertensives. Naltrexone should be used as an adjunct to a comprehensive alcohol treatment program that addresses concomitant medical problems and psychosocial concerns.
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PMID:Naltrexone for the treatment of alcoholism. 930 73

Clinical trials have shown that naltrexone is effective in treating alcohol dependence; nausea and dysphoria have been reported as "side effects" in many of these studies. In primates, naltrexone reduces reinforced responding for oral ethanol, sucrose, and phencyclidine. This study was designed to determine if naltrexone reduces reinforced responding for various solutions by producing an interoceptive stimulus that may result in a conditioned taste aversion. Four opioid antagonist-naive rhesus monkeys responded for solutions from a two-spout operant panel for 30 min per day. During a conditioning phase, the monkeys received novel Kool-Aid solutions paired with either saline or naltrexone (0.32 mg/kg) given 30 min before the session. The monkeys then had seven choice sessions between the saline-paired solution or the naltrexone-paired solution. During the conditioning phase, the naltrexone reduced responding after five naltrexone/solution pairings. In addition, a conditioned taste aversion was produced; the naltrexone-paired solution maintained significantly less responding than did the saline-paired solution during the choice phase. In the next phase, the saline and naltrexone were given "unpaired" from any distinct part of the operant session, and another seven choice sessions followed. Naltrexone had no effect when given "unpaired" from the operant session. Then, another conditioning phase was undertaken followed by another series of choice sessions. During the replication of the conditioning, naltrexone reduced responding by the second pairing, although no conditioned aversion was observed in the subsequent choice sessions. Thus, given in the same manner (dose, route, and pretreatment time) as situations in which naltrexone reduces oral ethanol-, sucrose-, and phencyclidine-reinforced responding, naltrexone produced a conditioned taste aversion. These results suggest that naltrexone-induced nausea and its conditioned effects should be considered in naltrexone's effect in alcoholics.
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PMID:Conditioned effects produced by naltrexone doses that reduce ethanol-reinforced responding in rhesus monkeys. 1023 7

Naltrexone, an opiate antagonist, is well tolerated by most alcoholic patients; however, a subset reports significant nausea that can limit the effectiveness of this therapy. The goal of this study was to identify risk factors for naltrexone-precipitated nausea to assist in the development of management strategies to maximize the overall effectiveness of naltrexone. On the basis of the hypothesis that alterations in the endogenous opioid system occur with repeated stimulation of endogenous opioids by alcohol, the authors predicted that the recency and intensity of alcohol use would be related to the risk of naltrexone-induced nausea. One hundred twenty alcohol-dependent subjects participated in an open-label trial of naltrexone. After 5 to 30 days of abstinence, subjects received an initial naltrexone dose of 25 mg followed by a dose of 50 mg daily thereafter for 10 weeks. New-onset adverse effects were rated mild, moderate, or severe after 1 week of naltrexone. Logistic regression analyses were used to predict moderate to severe nausea during the first week of therapy from pretreatment patient characteristics. Moderate to severe nausea was reported by 18 subjects (15%) and was linked to poorer medication compliance and heavier drinking during treatment. Risk of nausea was significantly predicted by age, gender, intensity of drinking, duration of abstinence, and the interaction of abstinence duration and intensity of drinking. At shorter durations of abstinence, lighter drinkers were more likely to experience nausea than heavier drinkers. However, the risk of nausea declined with longer periods of abstinence, particularly for lighter drinkers. Younger age and female gender were associated with higher rates of nausea. These results support the hypothesis that recency and intensity of alcohol use are related to opiate antagonist-precipitated nausea and suggest that long-term alcohol use may result in alterations in the endogenous opioid system. Potential strategies to minimize the risk of nausea in vulnerable individuals are discussed.
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PMID:Naltrexone-induced nausea in patients treated for alcohol dependence: clinical predictors and evidence for opioid-mediated effects. 1065 11

The present study was designed to test the short-term efficacy and safety of naltrexone in the treatment of pathological gambling disorder. Seventeen subjects (seven men, 10 women) who fulfilled DSM-IV criteria for pathological gambling disorder, and were free from other Axis I diagnoses by Structured Clinical Interview for DSM-III-R screening, participated in a 6-week open naltrexone flexible dose trial. Gambling symptom change was assessed with the patient-rated Clinical Global Impression (CGI) Scale, the clinician-rated CGI and the Gambling Symptom Assessment Scale. Side-effects were monitored weekly and liver function tests biweekly. Naltrexone reduced urges to gamble and gambling behaviour. The mean change in gambling frequency per week was 1.40 +/- 0.28 episodes per week; the mean change in dollars lost per week was $66.95 +/- 13.77; and the mean change in clinician-rated CGI Improvement was 0.40 +/- 0.04. Of those who responded to the medication, the majority had done so by the end of the fourth week. Men responded to naltrexone as well as women. The average naltrexone dose required for effective symptom control was 157 mg/day. Nausea was common during the first week (47%). The present findings provide evidence that naltrexone may be effective in the treatment of pathological gambling disorder. The present report is preliminary and controlled trials are needed to confirm these findings.
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PMID:An open naltrexone treatment study in pathological gambling disorder. 1155 72

Opioid receptor antagonist naltrexone has shown some efficacy in decreasing ethanol consumption in humans. However, naltrexone treatment is not always efficacious and produces several aversive effects such as nausea, anxiety and weight loss. Serotonin-3 (5-HT3) receptor antagonists also modulate some of the behavioral effects of alcohol and may decrease alcohol consumption. We examined the effects of the combination of 5-HT3 receptor antagonist ICS 205-930 ((3-tropanyl-indole-1-carboxylate, tropisetron) and naltrexone on ethanol and food intake in Sprague-Dawley rats. Both naltrexone (0.56-10 mg/kg) and ICS 205-930 (5.6 mg/kg), when administered intraperitoneally 30 min before the scheduled 3-h access to ethanol, significantly suppressed ethanol intake. Naltrexone (1 mg/kg) when given in combination with ICS 205-930 (5.6 mg/kg) was significantly more efficacious in suppressing ethanol intake in comparison with naltrexone (1 mg/kg) administered alone. The drug combination did not affect the food intake. These data suggest that 5-HT3 receptor antagonist ICS 205-930 may be used as an effective adjunct for pharmacotherapy of alcoholism.
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PMID:5-HT3 antagonist ICS 205-930 enhances naltrexone's effects on ethanol intake. 1514 Jun 31

Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea. Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviour per se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron. Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.
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PMID:Pharmacotherapy of alcohol dependence: a review of the clinical data. 1518 19


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