1

UI  - 20852

AU  - Monti PM

AU  - Rohsenow KE

AU  - Hutchison KE

AU  - Swift RM

AU  - Mueller TI

AU  - Colby SM

AU  - Brown RA

AU  - Gulliver SB

AU  - Gordon A

AU  - Abrams DB

TI  - Naltrexone's Effect on Cue-Elicted Craving Among Alcoholics In Treatment

AB  - 0145-6008

AV  - Bound Journal

SO  - Alcohol Clin Exp Res 2002 Aug ;23(8):1386-1394

2

UI  - 14500

AU  - Anton RF

AU  - Moak DH

AU  - Latham PK

AU  - Waid LR

AU  - Malcolm RJ

AU  - Dias JK

AU  - Roberts JS

AD  - Medical University of South Carolina, Alcohol Research Center, Charleston, USA. anton@musc.edu

TI  - Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism

AB  - Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol- dependent individuals may need prolonged treatment to improve treatment success in the long term

UR  - PM:11199951

SO  - J Clin Psychopharmacol 2001 Feb ;21(1):72-77

3

UI  - 14477

AU  - Carroll KM

AU  - Ball SA

AU  - Nich C

AU  - O'Connor PG

AU  - Eagan DA

AU  - Frankforter TL

AU  - Triffleman EG

AU  - Shi J

AU  - Rounsaville BJ

AD  - Department of Psychiatry, Yale University School of Medicine, VA CT Healthcare System, 950 Campbell Ave (151D), West Haven, CT 06516, USA. kathleen.carroll@yale.edu

TI  - Targeting behavioral therapies to enhance naltrexone treatment of opioid dependence: efficacy of contingency management and significant other involvement

AB  - BACKGROUND: Contingency management (CM) and significant other involvement (SO) were evaluated as strategies to enhance treatment retention, medication compliance, and outcome for naltrexone treatment of opioid dependence. METHODS: One hundred twenty-seven recently detoxified opioid-dependent individuals were randomly assigned to 1 of 3 conditions delivered for 12 weeks: (1) standard naltrexone treatment, given 3 times a week; (2) naltrexone treatment plus contingency management (CM), with delivery of vouchers contingent on naltrexone compliance and drug-free urine specimens; or (3) naltrexone treatment, CM, plus significant other involvement (SO), where a family member was invited to participate in up to 6 family counseling sessions. Principal outcomes were retention in treatment, compliance with naltrexone therapy, and number of drug-free urine specimens. RESULTS: First, CM was associated with significant improvements in treatment retention (7.4 vs 5.6 weeks; P =.05) and in reduction in opioid use (19 vs 14 opioid-free urine specimens; P =.04) compared with standard naltrexone treatment. Second, assignment to SO did not significantly improve retention, compliance, or substance abuse outcomes compared with CM. Significant effects for the SO condition over CM on retention, compliance, and drug use outcomes were seen only for the subgroup who attended at least 1 family counseling session. The SO condition was associated with significant (P =.02) improvements in family functioning. CONCLUSION: Behavioral therapies, such as CM, can be targeted to address weaknesses of specific pharmacotherapies, such as noncompliance, and thus can play a substantial role in broadening the utility of available pharmacotherapies

UR  - PM:11483141

SO  - Arch Gen Psychiatry 2001 Aug ;58(8):755-761

4

UI  - 14378

AU  - Church SH

AU  - Rothenberg JL

AU  - Sullivan MA

AU  - Bornstein G

AU  - Nunes EV

AD  - New York State Psychiatric Institute, Substance Treatment and Research Service, New York 10032, USA

TI  - Concurrent substance use and outcome in combined behavioral and naltrexone therapy for opiate dependence

AB  - The effect of concurrent nonopiate drug use on outcome of treatment for opiate dependence. METHOD: Forty-seven opiate-dependent patients received a 6-month course of outpatient treatment with naltrexone and cognitive-behavioral therapy (behavioral naltrexone therapy, BNT) at a university-based research clinic. Opiate-negative urines and naltrexone ingestion were rewarded with monetary vouchers. Abstinence from other drugs was encouraged verbally, but no contingencies were placed on nonopiate drug use. The proportions of all urines (collected twice weekly) positive for cocaine, cannabis, and benzodiazepines over the course of treatment were evaluated as predictors of outcome of opiate dependence treatment, as measured by proportion of opiate-positive urines, days retained in treatment, and proportion of naltrexone doses taken, using Pearson product moment correlations and one-way analysis of variance (ANOVA). RESULTS: The majority of patients (78%) used a nonopiate drug at least once during the trial. There were no significant correlations between concurrent drug use measures and opiate dependence treatment outcomes, indicating no simple linear relationship between these measures. However, when concurrent drug use was trichotomized into abstinent, intermittent, and heavy use groups, groups with intermittent use had superior outcome compared to both abstinent and heavy use groups in several contrasts. CONCLUSIONS: Intermittent use of nonopiate drugs is common during outpatient treatment for opiate dependence and may be a favorable prognostic indicator. This may support a "harm reduction" approach as opposed to a strict abstinence-oriented approach. Further research is needed to identify the optimal therapeutic stance toward other drug use during treatment for opiate dependence

UR  - PM:11506261

SO  - Am J Drug Alcohol Abuse 2001 Aug ;27(3):441-452

5

UI  - 19629

AU  - Feeney GF

AU  - Connor JP

AU  - Young RM

AU  - Tucker J

AU  - Czajkowski F

AD  - Alcohol and Drug Assessment Unit, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. Gerald-Feeney@health.qld.gov..au

TI  - Adherence with naltrexone prescription advice in hospital outpatient alcohol rehabilitation programme

AB  - BACKGROUND: The anti-craving drug, naltrexone, is used as a pharmacotherapeutic adjunct in the treatment of alcohol dependence. In addictive disorders, compliance issues remain central. There are limited data on compliance with naltrexone treatment regimens within formalized rehabilitation programs and even less data that identifies factors that have an impact on this. OBJECTIVE: To study patient adherence to naltrexone medication regimens and examine whether patients' reported pre-treatment alcohol use, dependence severity and measures of psychological health are predictive of medication compliance. METHOD: Fifty outpatients meeting DSM IV criteria for alcohol dependence enrolled in a 12-week rehabilitation programme. This included cognitive behavioural therapy (CBT) and naltrexone, 50 mg orally daily. Measures included: pharmacy prescription pick-up including number of tablets dispensed, programme attendance and patient pre-treatment alcohol use variables. Measures of psychological health included somatic symptoms, anxiety, social dysfunction and depression as measured by the General Health Questionnaire (GHQ-28). RESULTS: Classifying the sample into compliant (> or = 90% medication pick-up) and less compliant groups, 66% of subjects were naltrexone-compliant. Pre-treatment alcohol use variables were not predictive of compliance. Although social dysfunction and depression tended towards poorer prescription filling, measures of psychological distress (GHQ-28) did not identify factors predictive of medication non-compliance. One patient withdrew from treatment because of naltrexone-induced dysphoria. CONCLUSION: Patients with alcohol dependence demonstrated high levels of anti-craving medication compliance, good rehabilitation programme participation and favourable outcomes. Naltrexone was well tolerated. Medication compliance in this study group compared well with those of other hospital populations with chronic disorders. Factors predictive of anti-craving medication compliance in alcohol dependence require further study

UR  - PM:11286610

SO  - J Clin Pharm Ther 2001 Feb ;26(1):73-79

6

UI  - 20949

AU  - Feeney GFX

AU  - Young RM

AU  - Connor JP

AU  - Tucker J

AU  - McPherson A

TI  - Outpatient cognitive behavioural therapy programme for alcohol dependence impact of naltrexone use on outcome

AB  - Objective: Cognitive-behavioural therapy (CBT) has been effectively used in the treatment of alcohol dependence. Clinical studies report that the anticraving drug naltrexone, is a useful adjunct to treatment. Currently, few data are available on the impact of adding this medication to programmes in more typical, outpatient, and rehabilitation settings. The objective of this study was to examine the impact on outcome of adding naltrexone to an established outpatient alcohol rehabilitation program which employed CBT. Method: Fifty patients participated in an established 12-week, outpatient, 'contract'-based alcohol abstinence programme which employed CBT. They also received naltrexone 50 mg orally daily (CBT + naltrexone). Outcomes were compared with 50 historical, matched controls, all of whom participated in the same programme without an anticraving medication (CBT alone). All patients met DSM-IV criteria for alcohol dependence. Results: Programme attendance across the eight treatment sessions was lower in the CBT alone group (p < 0.001). Relapse to alcohol use occurred sooner and more frequently in the CBT alone group (p < 0.001). Rehabilitation programme completion at 12 weeks was 88% (CBT + naltrexone) compared with 36% for (CBT alone) (p < 0.001). Alcohol abstinence at 12 weeks was 76% (CBT + naltrexone) compared with 18% (CBT alone) (p < 0.001). Conclusion: When employing the same outpatient rehabilitation programme and comparing outcomes using matched historical controls, the addition of naltrexone substantially improves programme attendance, programme completion and reported alcohol abstinence. In a typical outpatient programme, naltrexone addition was associated with significantly improved programme participation, better outcomes and was well tolerated

IS  - 0004-8674

UR  - ISI:000171409200126

SO  - Australian and New Zealand Journal of Psychiatry 2001  ;35(4):443-448

7

UI  - 18367

AU  - Fuller RK

AU  - Gordis E

AD  - NIAAA, Bethesda, MD  20892

TI  - Naltrexone Treatment for Alcohol Dependence

AB  - Treatment for alcohol dependence has been limited almost entirely to various types of counseling. An exception has been the use of the medication disulfiram, which acts indirectly by making a person feel ill if he or she drinks alcohol. The efficacy of disulfiram is limited, however, because compliance is often poor, and it is not widely used. Counseling patients with alcoholism leads to rates of remission similar to those achieved with treatment of other chronic medical conditions, such as asthma.1 Nonetheless, the large number of people dependent on alcohol in the United States (over 8.1 million2) and the substantial costs of alcoholism to society - an estimated $185 billion and 100,000 deaths each year - make it imperative that treatment be improved. Thus, it is not surprising that reports in 19923,4 that the opiate antagonist naltrexone reduced the relapse rate in people dependent on alcohol generated substantial interest. The reports suggested that treatment could be improved through the use of medication in conjunction with counseling.

SO  - N Engl J Med 2001 Dec 13 ;345(24):1770-1771

8

UI  - 19626

AU  - Heinala P

AU  - Alho H

AU  - Kiianmaa K

AU  - Lonnqvist J

AU  - Kuoppasalmi K

AU  - Sinclair JD

AD  - National Public Health Institute, Department of Mental Health and Alcohol Research, Helsinki, Finland

TI  - Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial

AB  - Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time (12 weeks). In this study, 121 nonabstinent outpatients with alcohol dependence (DSM-IV) were treated with sessions of cognitive coping skills (N = 67) or supportive therapy (N = 54) and either naltrexone 50 mg/day (N = 63) or placebo (N = 58) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol (i.e., targeted medication) in a prospective one-center, dual, double-blind, randomized clinical trial. The dropout rate for all subjects was 16.5% during the first 12-week period and approximately twice that level by the end of the study. There were no significant group differences in study completion and therapy participation rates. After the continuous medication (12 weeks), the coping/naltrexone group had the best outcome, and coping/placebo had the worst. This difference remained during the targeted medication period (the following 20 weeks). Naltrexone was not better than placebo in the supportive groups, but it had a significant effect in the coping groups: 27% of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks, compared with only 3% of the coping/placebo patients. The authors' data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy. In addition, their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking

SO  - J Clin Psychopharmacol 2001 Jun ;21(3):287-292

9

UI  - 18366

AU  - Krystal JH

AU  - Cramer JA

AU  - Krol WF

AU  - Kirk GF

AU  - Rosenheck RA

TI  - Naltrexone in the Treatment of Alcohol Dependence

AB  - Background Although naltrexone, an opiate-receptor antagonist, has been approved by the Food and Drug Administration for the treatment of alcohol dependence, its efficacy is uncertain. Methods We conducted a multicenter, double-blind, placebo-controlled evaluation of naltrexone as an adjunct to standardized psychosocial treatment. We randomly assigned 627 veterans (almost all men) with chronic, severe alcohol dependence to 12 months of naltrexone (50 mg once daily), 3 months of naltrexone followed by 9 months of placebo, or 12 months of placebo. All patients were offered individual counseling and programs to improve their compliance with study medication and were encouraged to attend Alcoholics Anonymous meetings. Results There were 209 patients in each group; all had been sober for at least five days before randomization. At 13 weeks, we found no significant difference in the number of days to relapse between patients in the two naltrexone groups (mean, 72.3 days) and the placebo group (mean, 62.4 days; 95 percent confidence interval for the difference between groups, -3.0 to 22.8). At 52 weeks, there were no significant differences among the three groups in the percentage of days on which drinking occurred and the number of drinks per drinking day. Conclusions Our findings do not support the use of naltrexone for the treatment of men with chronic, severe alcohol dependence

SO  - N Engl J Med 2001 Dec 13 ;345(24):1734-1739

10

UI  - 20950

AU  - Monterosso JR

AU  - Flannery BA

AU  - Pettinati HM

AU  - Oslin DW

AU  - Rukstalis M

AU  - O'Brien CP

AU  - Volpicelli JR

TI  - Predicting treatment response to naltrexone: The influence of craving and family history

AB  - Naltrexone has repeated ly been shown to reduce drinking in alcohol-dependent patients. Previous clinical research suggests that naltrexone may be more effective at reducing drinking among patients with high levels of alcohol craving at the beginning of treatment. In addition, laboratory studies suggest that naltrexone may be more, efficacious among patients with a high familial loading of alcohol problems. We explored both of these possibilities in the context of the first 12-week phase of a double blind, placebo-controlled naltrexone trial. A total of 121 patients were randomized to receive 100 mg/day naltrexone and 62 patients were randomized to receive placebo. Both naltrexone and placebo were given in conjunction with a psychosocial intervention designed to be integrated with the use of pharmacotherapy. This intervention was administered by nurse practitioners. Overall, patients randomized to naltrexone reported drinking fire or more drinks on fewer days than did placebo controls (p =. 04). Interactions were observed between medication group assignment and both craving level prior to randomization (p = .02) and family loading of alcohol problems (p = .05). In both cases, the interaction was in the predicted direction. These data suggest that patients with high levels of alcohol craving or a strong family history of alcoholism are more likely to benefit from naltrexone treatment

SO  - American Journal on Addictions 2001  ;10(3):258-268

11

UI  - 14431

AU  - Monti PM

AU  - Rohsenow DJ

AU  - Swift RM

AU  - Gulliver SB

AU  - Colby SM

AU  - Mueller TI

AU  - Brown RA

AU  - Gordon A

AU  - Abrams DB

AU  - Niaura RS

AU  - Asher MK

AD  - Providence VA Medical Center (PMM, DJR, RMS); the Center for Alcohol and Addiction Studies, Brown University (PMM, DJR, RMS, SBG, SMC, MKA); Butler Hospital/Brown University (TIM, RAB, AG); and Butler Hospital/Brown University School of Medicine (DBA, RSN), Providence, Rhode Island

TI  - Naltrexone and Cue Exposure With Coping and Communication Skills Training for Alcoholics: Treatment Process and 1-Year Outcomes

AB  - BACKGROUND: Promising treatments for alcoholics include naltrexone (NTX), cue exposure combined with urge-specific coping skills training (CET), and communication skills training (CST). This study investigated the effects of combining these elements as treatment adjuncts. METHODS: A 2 x 2 design investigated the effects of CET combined with CST, as compared with an education and relaxation control treatment, during a 2- week partial hospital program (n = 165) followed by 12 weeks of NTX (50 mg/day) or placebo during aftercare (n = 128). Drinking outcomes were assessed at 3, 6, and 12 months after discharge from the partial hospital. Process measures included urge, self-efficacy (confidence about staying abstinent in risky situations), and self-reported coping skills. Medically eligible alcohol-dependent patients were recruited. RESULTS: Among those compliant with medication on at least 70% of days, those who received NTX had significantly fewer heavy drinking days and fewer drinks on days that they drank than those receiving placebo during the medication phase but not during the subsequent 9 months. CET/CST-condition patients were significantly less likely to report a relapse day and reported fewer heavy drinking days at the 6- and 12- month follow-ups than patients in the control treatment. Interactions of medication with behavioral treatments were not significant. Process measures showed that NTX resulted in lower weekly urge ratings, and those in CET/CST used more of the prescribed coping skills after treatment, reported fewer cue-elicited urges, and reported more self- efficacy in a posttest role-play test. Drinking reductions at 3, 6, and 12 months correlated with more use of coping skills, lower urge, and higher self-efficacy. CONCLUSIONS: The results suggest the probable value of keeping alcoholics on NTX for longer periods of time and the importance of increasing compliance with NTX. They also support the earlier promising effects of CET and CST as adjuncts to treatment programs for alcoholics by maintaining treatment gains over at least a year. The value of the urge-specific and general coping skills and of self-efficacy and urge constructs was demonstrated in their association with drinking outcomes

SO  - Alcohol Clin Exp Res 2001 Nov ;25(11):1634-1647

12

UI  - 14429

AU  - Sathe RS

AU  - Komisaruk BR

AU  - Ladas AK

AU  - Godbole SV

AD  - Maritosexual and Reproductive Research Institute (MARRI), Pune, Maharashtra, India. sexdoc9@hotmail.com

TI  - Naltrexone-induced augmentation of sexual response in men

AB  - BACKGROUND: To ascertain the role of endogenous opioids in sexual response, naltrexone, an opiate receptor antagonist, was administered to men, and its effect on selected self-report measures of sexual response to masturbation was recorded. METHODS: The data are based on results from 20 healthy, sexually active (alone or with a partner) men, aged 20-29 years, who ingested naltrexone (25 mg/day x 3) or placebo in a randomized, double-blind crossover design. There was at least a 14- day interval between drug and placebo treatment. Between 18 and 22 h after the most recent dose of drug or placebo, subjects viewed sexually explicit videos in privacy for 2 h. They were instructed to masturbate and have as many orgasms as desired. The following three different self- report measures of their responses were recorded: number of orgasms; intensity of sexual arousal, and orgasmic intensity. RESULTS: Under the naltrexone condition, the volunteers experienced a significantly greater mean number of orgasms (3.4 +/- 0.2 SEM) than under the placebo condition (2.6 +/- 0.3). The total number of orgasms was 67 under the naltrexone condition and 51 under the placebo condition. At the first orgasm, the measure of intensity of arousal was significantly greater in the naltrexone (3.9 +/- 0.2) than placebo (3.4 +/- 0.2) condition, and the measure of orgasmic intensity was significantly greater in the naltrexone (3.7 +/- 0.2) than in the placebo (3.0 +/- 0.3) condition. CONCLUSIONS: The present study provides evidence that endogenous opioids modulate orgasmic response and the perceived intensity of sexual arousal and orgasm in men. The findings suggest that naltrexone could be clinically useful in cases of inhibited sexual desire and erectile dysfunction

SO  - Arch Med Res 2001 May ;32(3):221-226

13

UI  - 14507

AU  - Sinclair JD

AD  - Department of Mental Health and Alcohol Research, National Public Health Institute (KTL), FIN-00101, Helsinki, Finland

TI  - Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism

AB  - Eight double-blind placebo-controlled clinical trials in five countries have demonstrated the safety and efficacy of naltrexone as an adjunct in alcoholism treatment. The efficacy depends, however, on how naltrexone is used. Three of the trials tested naltrexone in two ways: (1) with supportive therapy, i.e. support of complete abstinence; (2) with therapy tacitly accepting that relapses may occur and teaching how to cope with them. Although all found benefits from naltrexone with the coping therapy, none of them found any significant benefit of naltrexone over placebo when combined with support for abstinence. These results are consistent with our pre-clinical studies in which naltrexone, naloxone, and nalmefene were effective when paired with drinking but ineffective when given during abstinence. This supported the hypothesis that the primary mechanism involved is extinction (as had been concluded earlier for the effects of naltrexone in opiate addiction treatment), because extinction only weakens responses that are made while reinforcement is blocked. On this basis, it was proposed that: (1) naltrexone should be administered to patients who were still currently drinking; (2) the instructions should be to take naltrexone only when drinking was anticipated; (3) this treatment should continue indefinitely. Subsequently, clinical trials have found that naltrexone used in this manner is safe and effective

SO  - Alcohol Alcohol 2001 Jan ;36(1):2-10

14

UI  - 19428

AU  - Streeton C

AU  - Whelan G

TI  - Naltrexone, a relapse prevention maintenance treatment of alcohol dependence: A meta-analysis of randomized controlled trials

AB  - Reviewed the evidence for the efficacy and toxicity of naltrexone, a treatment of alcohol dependence. A systematic review and meta-analysis of randomized controlled trials of naltrexone used in the treatment of alcohol dependence was conducted. The authors searched MEDLINE, EMBASE, PsycLIT and the Cochrane Controlled Trials Registry for articles published from 1976 to January 2001. They analysed data from 7 studies that compared naltrexone to placebo, with the mean ages of patients ranging from 39 to 59 yrs. The meta-analysis of benefit indicates that naltrexone is superior to placebo. Ss treated with naltrexone experience significantly fewer episodes of relapse, and significantly more remain abstinent when compared to placebo-treated Ss after 12 wks of treatment. The naltrexone-treated Ss also consume significantly less alcohol over the study period than do placebo-treated Ss. There is no significant difference between naltrexone and placebo in terms of the number of Ss with at least 1 adverse event or the number of Ss who discontinued the trial due to an adverse event. (PsycINFO Database Record (c) 2000 APA, all rights reserved)

SO  - Alcohol & Alcoholism 2001  ;36(6):544-552

15

UI  - 19636

AU  - Chick J

AU  - Anton R

AU  - Checinski K

AU  - Croop R

AU  - Drummond DC

AU  - Farmer R

AU  - Labriola D

AU  - Marshall J

AU  - Moncrieff J

AU  - Morgan MY

AU  - Peters T

AU  - Ritson B

AD  - Department of Psychiatry, University of Edinburgh, University Department of Medicine, Royal Free Campus, The Royal Free and University College Medical School, London, UK

TI  - A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse

AB  - The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: < 0.05) and the reductions in alcohol craving (Obsessive and Compulsive Drinking Scale: OCDS) were greater in the naltrexone group (P: < 0.05), from approximately half-way through the study. Of 70 patients (35 placebo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P: < 0.05), had greater median reduction in serum GGT activity (P: < 0.05), and greater reduction in alcohol craving (OCDS total score: P: < 0.05; Obsessive subscale score: P: < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy, in patients who comply with treatment

MH  - abuse

SO  - Alcohol Alcohol 2000 Nov ;35(6):587-593

16

UI  - 14530

AU  - Middaugh LD

AU  - Lee AM

AU  - Bandy AL

AD  - Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, USA. middauld@musc.edu

TI  - Ethanol reinforcement in nondeprived mice: effects of abstinence and naltrexone

AB  - BACKGROUND: Operant experiments which indicate that ethanol can serve as a reinforcer to maintain lever responding during limited periods of access have not been conducted on non-food-deprived mice, as they have for rats and monkeys. Furthermore, there are no reports of the effects of chronic ethanol and subsequent abstinence on ethanol reward in mice. Finally, although naltrexone reduces responding for ethanol in food- deprived mice, the effects of the drug on ethanol reward for non-food- deprived mice have not been reported. METHODS: In three experiments, lever responding for ethanol (10-12%) was established in C57BL/6 (B6) mice by using either sucrose or saccharin fading procedures commonly used for rats. Experiment 1 examined both appetitive and consummatory responses while sucrose was faded from the ethanol solutions. Experiment 2 examined lever responding and ethanol intake (1) during saccharin fading; (2) when reinforcement schedules, reward availability, and primary conditioned reinforcers were manipulated; and (3) when mice were allowed chronic ethanol consumption followed by forced abstinence. Experiment 3 examined the effects of low doses of naltrexone on ethanol reward. RESULTS: Lever responding for ethanol can be established in non-food-deprived mice with the sucrose and saccharin fading procedures commonly used for rats. Lever responses increased with decreases in the reinforcer and increases in schedule demand, which indicated the reward value of the ethanol solution. Removal of ethanol from the solution reduced consumption with no change in the appetitive, instrumental response, which indicated that the two responses were under control of different stimuli, perhaps mediated by different neural mechanisms. Forced abstinence after chronic ethanol exposure increased responding for the drug, which suggested increased reward value. Naltrexone reduced responding as previously reported for food-deprived B6 mice. CONCLUSIONS: Ethanol appears to serve as a reinforcer for non-food-deprived or non-water-deprived B6 mice. Its reinforcing effects are increased by forced abstinence after chronic exposure and are decreased by naltrexone

MH  - abstinence

SO  - Alcohol Clin Exp Res 2000 Aug ;24(8):1172-1179

17

UI  - 13451

AU  - Pettinati HM

AU  - Volpicelli JR

AU  - Pierce JD

AU  - O'Brien CP

AD  - Department of Psychiatry, University of Pennsylvania, The Philadelphia Medical Center for Veteran Affairs, USA

TI  - Improving naltrexone response: an intervention for medical practitioners to enhance medication compliance in alcohol dependent patients10

AB  - The effectiveness of naltrexone, a FDA-approved medication for alcohol dependence, can be improved if we support and help patients to consistently take their medication. We illustrate how patient noncompliance with treatment negatively affects outcome, and, we describe a new intervention to enhance medication compliance. Outcome was evaluated for 196 alcohol dependent outpatients who were treated with 50 mg/day naltrexone or placebo for 12 weeks. For patients who adhered to the prescribed treatment, relapse rates were lower with naltrexone than placebo (10% vs. 38.6%, p < 0.001). For noncompliant patients, relapse rates were high and comparable between naltrexone- and placebo-treated patients (42.9% vs. 40%). In a second study of 100 alcohol dependent outpatients, we introduced an intervention that resulted in better medication compliance rates compared to a previous naltrexone study of patients who did not receive the intervention (77.0% vs. 60.8%, p < 0.01). This provided some support for the use of an intervention that targets medication compliance when prescribing naltrexone

SO  - J Addict Dis 2000  ;19(1):71-83

18

UI  - 14553

AU  - Rezvani AH

AU  - Overstreet DH

AU  - Mason GA

AU  - Janowsky DS

AU  - Hamedi M

AU  - Clark E Jr

AU  - Yang Y

TI  - Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats

AB  - It is common to treat some diseases with more than one medication simultaneously. Since more than one neurotransmitter system is involved in alcohol-seeking behaviour, then a therapeutic approach that targets more than one system should be more effective in reducing alcohol intake than one addressing a single system. To test this hypothesis, we compared the efficacy of low doses of individual drugs reported to reduce voluntary alcohol drinking to the efficacy of a mixture of these agents at the same low doses in reducing alcohol intake in three strains of alcohol-preferring rats (P, HAD, and Fawn-Hooded). After establishment of a stable baseline for alcohol intake in a continuous access paradigm, each rat received separate single i.p. injections of relatively low doses of either naltrexone (2.0 mg/kg), fluoxetine (1.0 mg/kg), the thyrotropin-releasing hormone analogue TA-0910 (0.2 mg/kg), a mixture of all three drugs, or the vehicle at 09:30. Each rat received all treatments, with an inter-injection washout period of at least 3 days. Alcohol and water intakes were measured at 6 and 24 h, and food intake was measured at 24 h, after the injection. Our results show that individual drugs did not significantly affect food, water, or alcohol intake. However, the mixture significantly reduced alcohol intake in all three strains, but had no effect on food intake. Similar results were obtained when the HAD rats received an oral dose of the individual drugs or the mixture. When P rats were given an i.p. injection of the mixture for 10 consecutive days, there was a continued suppressing effect. These findings show that a combination treatment designed to target simultaneously serotonergic, dopaminergic, and opioidergic systems can reduce alcohol intake, even though the doses of the individual drugs in the mixture are relatively low and ineffective when given singly

SO  - Alcohol Alcohol 2000 Jan ;35(1):76-83

19

UI  - 20960

AU  - Rohsenow DJ

AU  - Monti PM

AU  - Hutchison KE

AU  - Swift RM

AU  - Colby SM

AU  - Kaplan GB

TI  - Naltrexone's effects on reactivity to alcohol cues among alcoholic men

AB  - The mechanisms of naltrexone's effects on urges to drink during abstinence are unclear. Naltrexone may suppress either urges to drink specifically or appetitive responses in general. The effects of naltrexone on cue reactivity to alcoholic and sweet nonalcoholic beverages were investigated. Alcohol-dependent men (N = 53) in treatment received naltrexone (50 mg) or placebo. Four hours later, they received baseline assessment, exposure to fruit juice, and exposure to their usual alcoholic beverage in 3-min trials. Naltrexone reduced urge to drink and self- reported attention to the alcohol cues, not at the initial exposure but after repeated exposures to alcohol cues. Naltrexone reduced negative affect across baseline and alcohol trials. No effects of naltrexone on responses to the nonalcoholic appetitive beverage cues were found, suggesting that general appetite suppression does not mediate the effects of naltrexone on urges

SO  - Journal of Abnormal Psychology 2000  ;109(4):738-742

20

UI  - 20963

AU  - Rohsenow DJ

AU  - Colby SM

AU  - Monti PM

AU  - Swift RM

AU  - Martin RA

AU  - Mueller TI

AU  - Gordon A

AU  - Eaton CA

TI  - Predictors of compliance with naltrexone among alcoholics

AB  - Objective: Naltrexone has been found to be an effective adjunct to treatment to reduce the rate of drinking among alcoholics. However, adherence to the medication has been of considerable concern; the high rates of noncompliance with the medication limits the benefits that could potentially be realized from this pharmacotherapy. Knowledge of predictors of noncompliance could result in interventions targeted at these variables. Method: Participants were 128 alcohol-dependent patients who participated in a clinical placebo-controlled trial of naltrexone. Upon discharge from a 1- to 2-week partial hospital program, patients were randomly placed into 12 weeks of naltrexone (50 mg/day) or placebo (n = 64 per condition). Patients met with a physician and a research assistant weekly for 4 weeks then biweekly for 8 weeks. Results: Compliance (number of days taking medication) was not predicted by demographic or pretreatment alcohol use variables. Number and severity of side effects in the first week, particularly nausea and fatigue, predicted early termination. Compliance was not predicted by commitment to abstinence or self-efficacy about abstinence, but was greater among patients who believed more strongly that the medication would help them stay sober. Compliance was not predicted by general level of urge to drink during the first week on medication but compliance was greater among those with a higher urge to drink in response to alcohol stimuli in the laboratory. Conclusions: Implications for approaches to increase compliance include reducing side effects and increasing patients' beliefs in the efficacy of naltrexone

SO  - Alcoholism-Clinical and Experimental Research 2000  ;24(10):1542-1549

21

UI  - 13096

AU  - Volpicelli JR

AU  - Pettinati HM

AU  - et al

TI  - Improving naltrexone response:  An intervention for medical practitioners to enhance medication in alcohol dependent patients.

SO  - Journal of Addictive Diseases 2000  ;19():71-83

22

UI  - 14616

TI  - CSAT consensus panel supports expanded use of naltrexone for treatment of alcohol dependence. Center for Substance Abuse Treatment

SO  - Psychiatr Serv 1999 Mar ;50(3):437

23

UI  - 19659

AU  - Anton RF

AU  - Moak DH

AU  - Waid LR

AU  - Latham PK

AU  - Malcolm RJ

AU  - Dias JK

AD  - Alcohol Research Center, Medical University of South Carolina, Charleston 29425, USA

TI  - Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: Results of a placebo-controlled trial

AB  - OBJECTIVE: The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence. The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic populations and with a well-defined therapy. METHOD: In this study, 131 recently abstinent alcohol-dependent outpatients were treated with 12 weekly sessions of manual-guided cognitive behavioral therapy and either 50 mg/day of naltrexone (N = 68) or placebo (N = 63) (with riboflavin added as a marker of compliance) in a double-blind, randomized clinical trial. Alcohol consumption, craving, adverse events, and urinary riboflavin levels were assessed weekly. Levels of blood markers of alcohol abuse were also ascertained during the trial. RESULTS: The study completion, therapy participation, and medication compliance rates in the trial were high, with no differences between treatment groups. Naltrexone-treated subjects drank less, took longer to relapse, and had more time between relapses. They also exhibited more resistance to and control over alcohol-related thoughts and urges, as measured by a subscale of the Obsessive Compulsive Drinking Scale. Over the study period, 62% of the naltrexone group did not relapse into heavy drinking, in comparison with 40% of the placebo group. CONCLUSIONS: Motivated individuals with moderate alcohol dependence can be treated with greater effectiveness when naltrexone is used in conjunction with weekly outpatient cognitive behavioral therapy. Naltrexone increases control over alcohol urges and improves cognitive resistance to thoughts about drinking. Thus, the therapeutic effects of cognitive behavioral therapy and naltrexone may be synergistic

MH  - abuse

MH  - Adult

MH  - adverse

SO  - Am J Psychiatry 1999 Nov ;156(11):1758-1764

24

UI  - 14620

AU  - Davidson D

AU  - Palfai T

AU  - Bird C

AU  - Swift R

AD  - Department of Psychiatry, Indiana University School of Medicine, Indianapolis, USA

TI  - Effects of naltrexone on alcohol self-administration in heavy drinkers

AB  - The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad libitum alcohol drinking in a bar/restaurant setting were investigated in heavy beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received 50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized, double-blind crossover protocol. After 7 days of taking medication, subjects were provided with the opportunity to consume beer ad libitum during two, 90-min test sessions that were held 1 to 2 weeks apart. Blood samples were collected on test days to ensure medication compliance and to measure blood levels of NTX and the active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased urges to consume alcohol. NTX-treated subjects also took significantly longer to finish each glass of beer and were more likely to terminate beer drinking early. Self-report stimulation and ratings of positive mood states were lower during NTX treatment. Negative side effects of NTX, such as nausea and headache, were reported more frequently with NTX. Not all of the subjects decreased their beer intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not related to blood levels of the active metabolite beta-naltrexol or to a family history of alcoholism. Overall, the results of this study suggest that NTX affects a number of the components of alcohol drinking sequence, including lowering cravings, decreasing the positive reinforcing effects of alcohol, and increasing headache and nausea, each of which may contribute to reducing alcohol intake

SO  - Alcohol Clin Exp Res 1999 Feb ;23(2):195-203

25

UI  - 20993

AU  - Landabaso MA

AU  - Iraurgi I

AU  - Sanz J

AU  - Calle R

AU  - de Apodaka JR

AU  - Jimenez-Lerma JM

AU  - Gutierrez-Fraile M

TI  - Naltrexone in the treatment of alcoholism. Two-year follow up results

AB  - Aims: The usefulness of opioid antagonists in the treatment of alcoholism has been suggested both in the experimental and in the clinical field: Design: Randomized clinical trial. Methods: 30 patients who met the criteria for alcohol dependency or abuse (DSM IV), and who had undergone 3 or more aversion treatments in the last three pears were included. The patients were randomly distributed into two groups. The first group (NTX) (n=15) received a pharmacological treatment in the form of an aversion treatment for one year plus 25 mg of Naltrexone daily during the first 6 months; the second group was used as a Control, receiving aversion treatment daily for 12 months. Afterwards follow up controls were carried out with regard to the degree of abstinence/relapse after 12, 18, and 24 months. Results: The data are analyzed by means of a survival analysis (during the first 6 months) and a risk estimate (in the subsequent temporal controls). The probability of remaining abstinent during the first six months is greater in the NTX group than in the control group (p = 0.0244). One year after initiating the study/program, 73.3% of the NTX group subjects and 20% of the control group subjects remained abstinent (RR = 0.21; CI95% 0.06 to 0.81); after 2 years 40% of the experimental subjects remained abstinent, versus none of the controls (RR = 0.50; CI95% 0.28 to 0.88). Conclusion: We believe that the combined treatment of aversion and NTX would be effective in patients with multiple relapses, who are refractory to treatment; patients in whom the classic aversion treatment has shown to have a limited efficacy

SO  - European Journal of Psychiatry 1999  ;13(2):97-105

26

UI  - 14611

AU  - Middaugh LD

AU  - Kelley BM

AU  - Cuison ER

AU  - Groseclose CH

AD  - Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425, USA

TI  - Naltrexone effects on ethanol reward and discrimination in C57BL/6 mice

AB  - The effects of the opioid antagonist, naltrexone, on operant responding for oral ethanol reward delivered on a fixed-ratio schedule, and on the discriminative stimulus properties of intraperitoneally injected ethanol, was examined in two separate experiments. The ages, food/water motivational conditions, and naltrexone doses for the two experiments were similar to allow a direct comparison of naltrexone effects on the two measures. Male food-deprived C57BL/6 mice responded for ethanol during either preprandial (low thirst, high hunger motivation) or postprandial (high thirst, low hunger motivation tests). The reinforcing value of ethanol relative to water was greater during the preprandial tests; however, the amounts of ethanol consumed was greater during the postprandial tests, with some mice becoming unconscious during the 15-min test session. Naltrexone produced dose-responsive reductions in responding for ethanol under either testing condition. During postprandial tests, naltrexone reduced responding for ethanol reward at a dose (1.25 mg/kg) that had little effect on responding for water reward, suggesting some selectivity for ethanol reward. In addition, doses of naltrexone that reduced responding for ethanol rewards did not alter the discrimination of ethanol (g/kg) in an operant discrimination task, but did reduce the total number of responses made during these tests. Thus, under similar motivational and dosing conditions, the opiate antagonist attenuated the reinforcing, but not the discriminative properties of ethanol, suggesting that the latter is mediated by either different or additional neural mechanisms in C57BL/6 mice

MH  - age

MH  - alcohol

SO  - Alcohol Clin Exp Res 1999 Mar ;23(3):456-464

27

UI  - 14580

AU  - Monti PM

AU  - Rohsenow DJ

AU  - Hutchison KE

AU  - Swift RM

AU  - Mueller TI

AU  - Colby SM

AU  - Brown RA

AU  - Gulliver SB

AU  - Gordon A

AU  - Abrams DB

AD  - Providence VA Medical Center, Brown University, Rhode Island 02912, USA

TI  - Naltrexone's effect on cue-elicited craving among alcoholics in treatment

AB  - BACKGROUND: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high-risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory-based, cue-elicited urge to drink among abstinent alcoholics in treatment. METHODS: Alcohol-dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After approximately 1 week on medication, all received cue reactivity assessment. RESULTS: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue-elicited decreases in heart rate were not affected by the medication. CONCLUSIONS: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments

SO  - Alcohol Clin Exp Res 1999 Aug ;23(8):1386-1394

28

UI  - 20989

AU  - Namkoong K

AU  - Farren CK

AU  - O'Connor PG

AU  - O'Malley SS

TI  - Measurement of compliance with naltrexone in the treatment of alcohol dependence: Research and clinical implications

AB  - Background: Medication compliance is a critical issue in pharmacotherapy. This study evaluated the clinical utility of the Medication Event Monitoring System (MEMS), a newer method for monitoring medication compliance, compared with pill count, a traditional measure, in a sample of patients heated for alcohol dependence with naltrexone. Method: Ninety-three outpatients meeting DSM-III-R criteria for alcohol dependence participated in a 10-week open-label study of naltrexone. They were provided with naltrexone, 50 mg daily, and concurrent counseling. Measures of medication compliance and drinking during treatment were collected every 2 weeks. Results: Pill count yielded a significantly (p <.001) higher estimate of compliance (87.6% +/- 18.1%) than the MEMS (80.4% +/- 20.6%). However, the estimate of compliance obtained with the MEMS was more consistently correlated with treatment outcome (percentage of days abstinent, percentage of heavy drinking days, and mean alcohol amount consumed per drinking occasion) than the pill count compliance rate. In addition, classification of the sample into compliant and less compliant groups using the:MEMS data yielded groups that differed more clearly on drinking outcomes than did stratification on the basis of pill count. Conclusion: In pharmacotherapy research, the MEMS may provide more reliable and valid information about subjects' medication compliance than pill count. Clinically, information obtained with the MEMS could be used to provide feedback to patients about their pill-taking behavior to enhance compliance and overall outcome of therapy

MH  - abuse

SO  - Journal of Clinical Psychiatry 1999  ;60(7):449-453

29

UI  - 14603

AU  - Williams KL

AU  - Woods JH

AD  - Department of Psychology, University of Michigan, Ann Arbor 48109-0632, USA

TI  - Conditioned effects produced by naltrexone doses that reduce ethanol- reinforced responding in rhesus monkeys

AB  - 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

SO  - Alcohol Clin Exp Res 1999 Apr ;23(4):708-715

30

UI  - 14631

AU  - Osser DN

AD  - Harvard Medical School, USA

TI  - How is naltrexone used in the treatment of alcoholism?

SO  - Harv Ment Health Lett 1998 Dec ;15(6):8

31

UI  - 19725

AU  - Farren CK

AU  - O'Malley S

TI  - Sequential use of naltrexone in the treatment of relapsing alcoholism

SO  - Am J Psychiatry 1997 May ;154(5):714

32

UI  - 17793

AU  - Galarza NJ

AU  - Diaz RD

AU  - Guzman F

AU  - Caballero JA

AU  - Martinez AJ

AD  - Department of Psychiatry, University of Puerto Rico, San Juan

TI  - The use of naltrexone to treat ambulatory patients with alcohol dependence

AB  - The purpose of this study is to evaluate the efficacy of Naltrexone in decreasing craving symptoms among Puerto Rican male veterans with alcohol dependence. METHOD: This is a double blind placebo control study with a convenience sample of eleven patients divided in two groups (placebo and Naltrexone). Scales consisting of Zung Depression, Zung Anxiety, MMSE, OCD Screener, Craving, and Somatization were administered at baseline, and weekly for four weeks as follow up. RESULTS: There were no statistically significant differences between the two groups on any of the outcome variables at baseline or follow up measurements. A statistical trend was noted toward a decrease in somatization. A decrease in craving symptoms was observed in the experimental group. CONCLUSIONS: Even though our results did not show evidence of the efficacy of Naltrexone in decreasing craving symptoms, a small number of patients did benefit from the medication. The results could have been affected by the small sample size

SO  - Bol Asoc Med P R 1997 Oct ;89(10-12):157-160

33

UI  - 19724

AU  - Kranzler HR

AU  - Tennen H

AU  - Penta C

AU  - Bohn MJ

AD  - Department of Psychiatry, University of Connecticut Health Center, Farmington 06030-2103, USA

TI  - Targeted naltrexone treatment of early problem drinkers

AB  - Naltrexone is approved for daily use in the treatment of alcohol dependence. We evaluated the feasibility of using targeted naltrexone (i.e., on an "as-needed" basis) to treat early problem drinkers. Twenty-one subjects (52% male) received brief coping skills training weekly for 4 weeks, along with naltrexone (50 mg), which they were instructed to use 2 to 5 times per week in anticipation of high-risk drinking situations. During treatment, statistically and clinically significant declines were observed across a variety of drinking-related outcomes, including the intensity of drinking, the decline in which was correlated with medication use. Beneficial effects of the intervention were still evident during the 3-month posttreatment period. Further research, including a placebo-controlled evaluation of targeted naltrexone, is needed to determine the optimal treatment strategy for early problem drinkers, many of whom are seen in the primary-care medical setting

SO  - Addict Behav 1997 May ;22(3):431-436

34

UI  - 17809

AU  - Modesto-Lowe V

AU  - Burleson JA

AU  - Hersh D

AU  - Bauer LO

AU  - Kranzler HR

AD  - Alcohol Research Center, University of Connecticut Health Center, Farmington 06030, USA

TI  - Effects of naltrexone on cue-elicited craving for alcohol and cocaine

AB  - This study examined the effects of naltrexone (50 mg/day) on mood and self-reported desire for alcohol and cocaine in 26 patients with comorbid alcohol and cocaine abuse/dependence. Two laboratory sessions were conducted, separated by 1 week. During the sessions, subjects viewed 5-min films containing either cocaine, alcohol, or neutral cues. The first session occurred prior to random assignment to medication group and the second session was held after 1 week of double-blind treatment with either naltrexone or placebo. The cocaine-related film induced a greater desire to use cocaine than the desire for alcohol that was induced by the alcohol-related film. This finding was observed using both a simple, one-item analog scale administered during the films and more complex craving questionnaires administered immediately after the films. Collectively, the alcohol and cocaine-related films evoked greater levels of self-reported anxiety and elation, and lower levels of concentration, than the neutral film. Naltrexone did not differ from placebo in reducing the desire to use either cocaine or alcohol

SO  - Drug Alcohol Depend 1997 Dec ;49(1):9-16

35

UI  - 19709

AU  - O'Connor PG

AU  - Farren CK

AU  - Rounsaville BJ

AU  - O'Malley SS

AD  - Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8025, USA

TI  - A preliminary investigation of the management of alcohol dependence with naltrexone by primary care providers

AB  - PURPOSE: To describe a preliminary investigation of a model of naltrexone therapy and counselling for use by primary care providers and evaluate its impact on drinking behaviors in a cohort of alcohol-dependent subjects. PATIENTS AND METHODS: The subjects enrolled in this study were 29 alcohol-dependent individuals. They were managed within a primary care treatment model located at a university-affiliated substance research program in New Haven, Connecticut. Subjects were assigned to a primary care provider for treatment of their alcohol dependence and were placed on naltrexone at a dose of 50 mg per day. They were seen for an initial "new patient" visit and 7 "brief" follow-up visits during the 10-week study. The primary outcomes for this study were completion of treatment, change in drinking behaviors from baseline, change in liver enzymes from baseline, provider ratings of improvement, and patient ratings of improvement and satisfaction with treatment. RESULTS: Of the 29 subjects: 21 (72%) completed treatment, and 10 (35%) relapsed to heavy drinking. All drinking behaviors improved significantly from baseline: percent of days abstinent increased from 36.6% to 88.8% (P < 0.0001), percent days abstinent from heavy drinking increased from 48.7% to 97.3% (P < 0.0001), and mean number of drinks per occasion decreased from 9.5 to 2.5 (P < 0.0001). The mean serum gamma glutamyl transferase (GGT) for the group decreased from 67.1 U/L to 45.3 U/L (P < 0.0001). CONCLUSIONS: In this preliminary investigation, treatment of alcohol dependence with our model of naltrexone and counselling by primary care providers appeared to be both feasible and effective

SO  - Am J Med 1997 Dec ;103(6):477-482

36

UI  - 17817

AU  - Phillips TJ

AU  - Wenger CD

AU  - Dorow JD

AD  - Veterans Affairs Medical Center, Portland, OR 97201, USA

TI  - Naltrexone effects on ethanol drinking acquisition and on established ethanol consumption in C57BL/6J mice

AB  - Naltrexone's success as a treatment agent for alcoholism seems to be due to its ability to reduce craving in abstinent, dependent individuals and to reduce the pleasure associated with subsequent intake. However, more study is needed to establish the optimal amount of time that naltrexone treatment should be continued. Little information seems to have been collected regarding the most effective dosing regimen for reducing alcohol craving and consumption, and the usefulness of opiate antagonists in the prevention of alcohol dependence in nonaddicts, rather than just as a treatment agent in addicted individuals, also deserves further study. The alcohol- preferring C57BL/6J (B6) mice were used to: (1) study naltrexone effects on consumption in established drinkers using an increasing dosing regimen, (2) study naltrexone effects on the acquisition of ethanol drinking, and (3) study the effects of chronic naltrexone from timed-release pellets on drinking in alcohol-naive mice. Naltrexone reduced ethanol preference in established drinkers, but its effects waned at increasing doses. Naltrexone slowed the acquisition of ethanol drinking, but was ineffective when readministered after a phase when ethanol was offered in the absence of naltrexone. Mice with chronic naltrexone pellets consumed greater amounts of ethanol and showed higher ethanol preference than did placebo-pelleted animals. The observed reduced efficacy of naltrexone with increasing dosage and chronic treatment may have been due to naltrexone-induced opiate receptor changes. Such changes are presumably more likely to occur when naltrexone doses remain high or perhaps accumulate. Thus, dose and frequency of administration may be important factors in determining naltrexone's effectiveness in treating alcohol dependence

SO  - Alcohol Clin Exp Res 1997 Jun ;21(4):691-702

37

UI  - 13477

AU  - Volpicelli JR

AU  - Rhines KC

AU  - Rhines JS

AU  - Volpicelli LA

AU  - Alterman AI

AU  - O'Brien CP

AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia, USA

TI  - Naltrexone and alcohol dependence. Role of subject compliance40

AB  - BACKGROUND: Two previous double-blind, placebo-controlled studies demonstrated that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects. In both studies, treatment compliance was excellent. However, a robust treatment effect size for naltrexone relative to placebo has been shown for compliant subjects but not for subjects who missed research visits. The goal of this study was to determine the effectiveness of naltrexone in subjects who received psychosocial treatment in a more naturalistic setting with respect to the role of treatment attendance and medication compliance. METHODS: Ninety-seven alcohol-dependent subjects were randomly assigned to receive either naltrexone (n = 48) or matching placebo (n = 49) for 12 weeks. All subjects received individual counseling (twice per week for the first month followed by once per week). RESULTS: Overall, naltrexone showed only modest effects in reducing alcohol drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy improved across a variety of outcome measures for subjects who completed treatment and were highly compliant with taking medication. CONCLUSIONS: Naltrexone is clinically effective relative to placebo in individuals who comply with the treatment protocol and take medication. The modest treatment effects in the entire sample suggest that the clinical efficacy of naltrexone could be improved by enhancing treatment compliance

SO  - Arch Gen Psychiatry 1997 Aug ;54(8):737-742

38

UI  - 19010

AU  - Wold M

AU  - Kaminer Y

TI  - Naltrexone for alcohol abuse

SO  - J Am Acad Child Adolesc Psychiatry 1997 Jan ;36(1):6-7

39

UI  - 19737

AU  - Davidson D

AU  - Swift R

AU  - Fitz E

AD  - Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island, USA

TI  - Naltrexone increases the latency to drink alcohol in social drinkers

AB  - We investigated the effects of naltrexone (NTX) on alcohol drinking, urge to drink alcohol, and alcohol-induced sensations and mood states in social drinkers consuming alcohol ad libitum in a cocktail bar. Sixteen college-age men and women participated in a double-blind, placebo-controlled, within-subjects, cross-over study. Subjects were tested during each of three drug conditions: NTX, 50 mg/ day, po; inactive placebo; and no drug. Each treatment condition lasted 8 to 11 days. Small groups of subjects consumed alcohol ad libitum during three 2-hr evening drinking sessions, separated by approximately-2 weeks. NTX treatment significantly increased the latency (time in seconds) to first sip the first (p < 0.05) and second alcoholic beverages consumed (p < 0.01). Moreover, the mean blood alcohol concentration at the end of the session was significantly lower when subjects were treated with NTX (p < 0.05). No differences were found on self-report urge to drink alcohol. Subjects reported more fatigue and tension on the Profile of Mood States (p < 0.05), before drinking, and increases in nausea on the Alcohol Sensation Scale (p < 0.05) when treated with NTX. The increase in the latency to sip the first and second alcoholic beverages may reflect the capacity of NTX to block urge for alcohol elicited from external cues (before consuming alcohol), as well as urge for alcohol after priming from ingested alcohol. Thus, the effectiveness of NTX for reducing drinking behaviors of alcoholics may be partially caused by anticraving properties of NTX

SO  - Alcohol Clin Exp Res 1996 Jun ;20(4):732-739

40

UI  - 13494

AU  - O'Brien CP

AU  - Volpicelli LA

AU  - Volpicelli JR

AD  - Center for the Study of Addiction, University of Pennsylvania, Philadelphia 19104-6178, USA

TI  - Naltrexone in the treatment of alcoholism: a clinical review58

AB  - The pooled results from our Veterans Affairs studies are presented for 99 men. The naltrexone-treated subjects reported a reduction in alcohol craving and drinking, as well as less euphoria when they ingested alcohol. Relapse rates were significantly lower for the naltrexone- treated subjects than they were for placebo-treated subjects. Together with the consistent results from other double-blind trials of naltrexone, we conclude that naltrexone is a safe and useful adjunct in the rehabilitation of alcohol-dependent patients. Although administration of naltrexone was shown to improve treatment outcome, subjects who attended all 12 research visits demonstrated larger treatment effects. These data suggest that the use of naltrexone as a pharmacological adjunct to psychosocial intervention is an effective treatment for alcohol dependence. The effectiveness of naltrexone may be improved by designing a treatment program that enhances compliance with the medication

SO  - Alcohol 1996 Jan ;13(1):35-39

41

UI  - 17816

AU  - O'Malley SS

AU  - Jaffe AJ

AU  - Rode S

AU  - Rounsaville BJ

AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA

TI  - Experience of a "slip" among alcoholics treated with naltrexone or placebo

AB  - OBJECTIVE: This study tested the hypothesis that naltrexone reduces relapse rates among alcoholics by modifying the reinforcing effects of initial alcohol consumption and alcohol-induced craving. METHOD: Sixteen alcoholic patients treated with naltrexone and 27 treated with placebo who participated in a 12-week clinical trial reported retrospectively on their subjective responses to their first episode of a lapse into alcohol consumption and on their reasons for terminating the drinking episode. RESULTS: Compared to the subjects who received placebo, the subjects who received naltrexone reported lower levels of craving for alcohol and were more likely to give reasons for terminating drinking that were consistent with decreased incentive to drink. CONCLUSIONS: These findings support the hypothesis that a central effect of naltrexone is the modification of alcohol-induced craving

SO  - Am J Psychiatry 1996 Feb ;153(2):281-283

42

UI  - 19446

AU  - O'Malley SS

AU  - Jaffe AJ

AU  - Chang G

AU  - Rode S

AU  - Schottenfeld R

AU  - Meyer RE

AU  - Rounsaville B

AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, Conn, USA

TI  - Six-month follow-up of naltrexone and psychotherapy for alcohol dependence

AB  - BACKGROUND: The goal of this study was to examine the persistence of naltrexone's effects on drinking outcomes among alcoholics following discontinuation of treatment and to determine whether coping skills therapy improves long-term outcomes compared with supportive therapy. METHODS: Eighty of 97 alcohol-dependent subjects randomized to receive naltrexone or placebo and either coping skills therapy or supportive therapy for 12 weeks were assessed at a 6-month off-treatment follow-up. RESULTS: Subjects who received naltrexone were less likely to drink heavily or to meet criteria for alcohol abuse or dependence than subjects who received placebo. The effect of naltrexone therapy on abstinence rates persisted only through the first month of follow-up. Coping skills therapy was associated with decreased levels of drinking among subjects who received placebo. Psychotherapy condition, however, did not predict alcohol diagnosis at follow-up. CONCLUSIONS: Some but not all of the benefits resulting from short-term naltrexone treatment persist after discontinuation of treatment. The findings suggest that continued treatment with naltrexone may be beneficial for some patients

SO  - Arch Gen Psychiatry 1996 Mar ;53(3):217-224

43

UI  - 19731

AU  - Overstreet DH

AD  - Skipper Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, USA

TI  - Alternatives to naltrexone in animal models

SO  - Alcohol Clin Exp Res 1996 Nov ;20(8 Suppl):231A-235A

44

UI  - 19746

AU  - Brewer C

TI  - Naltrexone in alcohol dependence

SO  - Lancet 1995 Nov 18 ;346(8986):1374

45

UI  - 14497

AU  - Doty PP

AU  - de Wit HH

AD  - Department of Psychiatry, MC3077, University of Chicago, Chicago, IL 60637, USA

TI  - Effects of naltrexone pretreatment on the subjective and performance effects of ethanol in social drinkers

AB  - Clinical trials suggest that opioid antagonists may be effective in the treatment of alcoholism. For example, two recent clinical trials reported that alcoholics treated with the opioid antagonist naltrexone exhibited higher abstinence rates, decreased craving and a decrease in the amount of alcohol consumed if drinking occurred. The present study examined the hypothesis that naltrexone pretreatment would attenuate the behavioral responses to an acute dose of ethanol in normal, healthy social drinkers. Thirteen healthy male and female social drinkers participated in a six-session, double-blind, placebo-controlled, crossover design study. On each session, subjects ingested a capsule containing naltrexone (25 or 50mg) or placebo and one hour later consumed a beverage containing ethanol (0.5g/kg) or placebo. For three hours after the beverage was consumed, breath alcohol levels were measured and subjects completed standardized subjective effects questionnaires and performance tasks at regular intervals. Ethanol alone produced its prototypic effects, including positive subjective responses such as euphoria and increased ratings of overall liking, as well as increased ratings of confusion. Ethanol also impaired performance on a verbal recall task. Naltrexone alone produced few subjective effects and did not impair psychomotor or verbal recall performance. Contrary to our hypothesis, pretreatment with naltrexone did not alter the positive subjective effects, or any other effects, of ethanol. Further research is needed to determine the influence of factors such as baseline level of ethanol consumption or duration of naltrexone treatment on the interaction between ethanol and the endogenous opioid system

SO  - Behav Pharmacol 1995 Jun ;6(4):386-394

46

UI  - 19757

AU  - Swift RM

AD  - Department of Psychiatry, Roger Williams Medical Center, Providence, RI 02908, USA

TI  - Effect of naltrexone on human alcohol consumption

AB  - Opioid neurotransmitter systems have been shown to mediate certain aspects of alcohol consumption in animals and in humans. Use of opioid antagonists appears to decrease alcohol consumption in animals. Controlled clinical trials have indicated that alcohol-dependent subjects who are treated with a combination of naltrexone, an opioid antagonist, and traditional psychological and social therapies consume less alcohol and have lower relapse rates. The neurobiological mechanisms by which naltrexone acts to reduce alcohol consumption are still being investigated; however, there is evidence that naltrexone modifies the reinforcing effects of alcohol. Some researchers suggest that the reinforcing stimulant effects of alcohol and other psychoactive substances play a primary role in initiating and maintaining substance abuse and dependence. These effects may be mediated through the action of endogenous opioids. This article discusses the possible mechanisms of action of naltrexone and reviews human and animal studies that support the use of naltrexone in the treatment of alcohol dependence

SO  - J Clin Psychiatry 1995  ;56 Suppl 7():24-29

47

UI  - 12221

AU  - Swift RM

AU  - Whelihan W

AU  - Kuznetsov O

AU  - Buongiorno G

AU  - Hsuing H

TI  - Naltrexone-induced alterations in human ethanol intoxication

NT  - OBJECTIVE: Outpatient clinical trials with an opioid antagonist, naltrexone, found that this agent reduces relapse drinking in abstinent alcoholics. It is unknown which aspects of intoxication may be affected by naltrexone. The authors investigated the effects of naltrexone on several subjective and objective measures of ethanol intoxication. METHOD: In a double-blind crossover study, 19 nonalcoholic drinkers received a regimen of naltrexone, 50 mg p.o., or placebo on two different occasions, each time followed by a standard, intoxicating dose of ethanol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and ethanol pharmacokinetics were determined. As a control for naltrexone effects, 12 additional subjects received naltrexone or placebo followed by a non-intoxicating, "placebo" dose of ethanol. RESULTS: Naltrexone augmented certain sedative and discriminant effects of ethanol and reduced positive reinforcing effects without affecting psychomotor performance or ethanol pharmacokinetics. Naltrexone had minimal effects in subjects receiving placebo ethanol. CONCLUSIONS: The data are compatible with the clinical findings and suggest that the reduction in ethanol consumption by alcoholics following naltrexone administration may occur because of greater subjective intoxication, greater aversive effects, or less positive reinforcement from ethanol

SO  - Am J Psychiatry 1994 Oct 1995  ;151():1463-1467

48

UI  - 17829

AU  - Volpicelli JR

AU  - Watson NT

AU  - King AC

AU  - Sherman CE

AU  - O'Brien CP

AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia 19104

TI  - Effect of naltrexone on alcohol "high" in alcoholics

AB  - OBJECTIVE: Subjective effects of alcohol in alcoholics treated with naltrexone or placebo were compared. METHOD: In a previously reported double-blind clinical trial of 50 mg/day of naltrexone or placebo for treatment of alcoholism, 36 of 70 detoxified male veterans deviated from abstinence. Of these 36, 29 subsequently reported on the subjective effects of drinking during the trial. RESULTS: A larger proportion of naltrexone-treated subjects (seven of 12) than placebo- treated subjects (two of 17) reported that the "high" produced by alcohol during the study was significantly less than usual. The naltrexone-treated subjects also drank less alcohol than the placebo- treated subjects during the first drinking episode. There was no difference between groups in reported intoxication, craving, memory, or loss of temper. CONCLUSIONS: The lower alcohol consumption by the naltrexone-treated subjects may have resulted from naltrexone's blockage of the pleasure produced by alcohol

SO  - Am J Psychiatry 1995 Apr ;152(4):613-615

49

UI  - 13496

AU  - Volpicelli JR

AU  - Volpicelli LA

AU  - O'Brien CP

AD  - Department of Psychiatry and Psychology, University of Pennsylvania, Philadelphia 19104, USA

TI  - Medical management of alcohol dependence: clinical use and limitations of naltrexone treatment61

AB  - Historically, pharmacological and psychosocial treatments for alcohol dependence have demonstrated only modest effectiveness in reducing alcohol drinking. However, the recent US Food and Drug Administration approval of naltrexone for the treatment of alcohol dependence offers a new, safe and effective medication to reduce relapse following alcohol detoxification. This paper reviews the various psychosocial and pharmacological treatments currently available and the effectiveness of these treatments. This paper also reviews preclinical research which demonstrates the involvement of the opioid system in the reinforcing effects of alcohol. This research led to clinical trials on the use of the opioid antagonist, naltrexone, to reduce alcohol's pleasurable effects and enhance the effectiveness of psychosocial therapy. In two randomized clinical trials, naltrexone treatment reduced rates of alcohol relapse, number of drinking days and alcohol craving. The clinical efficacy of all pharmacological treatments for substance abuse are limited by compliance with taking the medication. Also, pharmacological treatment does not address the psychosocial complications which often result from chronic alcohol dependence. Therefore, the integration of medications such as naltrexone and psychosocial therapies may offer the best treatment. The further development and investigation of new pharmacological agents will enable matching of patient populations with specific treatments, offering more successful treatment outcomes

SO  - Alcohol Alcohol 1995 Nov ;30(6):789-798

50

UI  - 19748

AU  - Volpicelli JR

AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia, USA

TI  - Naltrexone in alcohol dependence

SO  - Lancet 1995 Aug 19 ;346(8973):456

51

UI  - 13732

AU  - Sax DS

AU  - Kornetsky C

AU  - Kim A

AD  - Department of Neurology, Boston University School of Medicine, Massachusetts

TI  - Lack of hepatotoxicity with naltrexone treatment15

AB  - Naltrexone, a specific opiate receptor antagonist, is used clinically in the treatment of heroin addiction and more recently, for the treatment of dyskinesia associated with Huntington's disease (HD). Naltrexone may act as a potential hepatotoxin, as reflected in the elevation of transaminase levels. However, one study concluded that, for a brief treatment period of 12 weeks, there is no contraindication to naltrexone treatment based solely on increased hepatic enzyme values. This study monitored liver transaminase levels, in ten HD patients receiving daily doses, between 50 mg/day and 300 mg/day, of naltrexone for periods of 10 to 36 months. Serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were obtained before treatment and at intervals of 1 to 4 months during treatment. Only one of the ten patients treated with naltrexone had increased levels of both SGOT and SGPT, whereas one other patient showed elevated levels of SGPT. These elevations, which initially appeared dose related decreased to normal limits with continued treatment. Because many of the patients were receiving other medications, a combination of drugs with naltrexone may contribute to the increased transaminase levels seen in two of the patients. In summary, chronic administration of naltrexone in doses up to 300 mg/day for periods up to 36 months does not significantly change hepatic function, as measured by SGOT and SGPT levels

MH  - addiction

SO  - J Clin Pharmacol 1994 Sep ;34(9):898-901

52

UI  - 19758

AU  - Swift RM

AU  - Whelihan W

AU  - Kuznetsov O

AU  - Buongiorno G

AU  - Hsuing H

AD  - Department of Psychiatry and Human Behavior, Brown University Medical School, Providence, RI

TI  - Naltrexone-induced alterations in human ethanol intoxication

AB  - OBJECTIVE: Outpatient clinical trials with an opioid antagonist, naltrexone, found that this agent reduces relapse drinking in abstinent alcoholics. It is unknown which aspects of intoxication may be affected by naltrexone. The authors investigated the effects of naltrexone on several subjective and objective measures of ethanol intoxication. METHOD: In a double-blind crossover study, 19 nonalcoholic drinkers received a regimen of naltrexone, 50 mg p.o., or placebo on two different occasions, each time followed by a standard, intoxicating dose of ethanol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and ethanol pharmacokinetics were determined. As a control for naltrexone effects, 12 additional subjects received naltrexone or placebo followed by a non-intoxicating, "placebo" dose of ethanol. RESULTS: Naltrexone augmented certain sedative and discriminant effects of ethanol and reduced positive reinforcing effects without affecting psychomotor performance or ethanol pharmacokinetics. Naltrexone had minimal effects in subjects receiving placebo ethanol. CONCLUSIONS: The data are compatible with the clinical findings and suggest that the reduction in ethanol consumption by alcoholics following naltrexone administration may occur because of greater subjective intoxication, greater aversive effects, or less positive reinforcement from ethanol

SO  - Am J Psychiatry 1994 Oct ;151(10):1463-1467

53

UI  - 9873

AU  - Cote TE

AU  - Izenwasser S

AU  - Weems HB

TI  - Naltrexone-induced upregulation of mu opioid receptors on 7315c cell and brain membranes: enhancement of opioid efficacy in inhibiting adenylyl cyclase

NT  - 94046539 Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland The effect of chronic naltrexone administration on the expression of mu opioid receptors on 7315c tumor cells was examined. Osmotic minipumps containing either saline or naltrexone were subcutaneously implanted into Buffalo rats that had been injected intraperitoneally with 7315c cells. Fourteen days after the pumps were implanted, 7315c tissue and brain tissue were removed and examined for their ability to bind [3H]DAMGO and to respond to morphine (or DAMGO) and guanosine 5'- O-(3-thiotriphosphate) in an adenylyl cyclase assay. Naltrexone treatment caused a doubling in the density of [3H]DAMGO binding sites in both whole brain membranes and the 7315c cell membranes. Naltrexone treatment may have slightly diminished the affinity of mu opioid receptors for [3H]DAMGO (by 1.5- to 2-fold), but the precision of the assay was inadequate to determine whether this difference was significant. Naltrexone treatment also had no effect on the potency or efficacy of guanosine 5'-O-(3- thiotriphosphate) in diminishing [3H]DAMGO binding to either whole brain or 7315c cell membranes. The influence of naltrexone treatment on opioid inhibition of adenylyl cyclase activity was also investigated in both tissues. In 7315c membranes, naltrexone treatment caused a 40% increase in the efficacy (maximal effect) of morphine but had no effect on the potency (IC50) of morphine in inhibiting forskolin-stimulated adenylyl cyclase activity. In whole brain membranes from control rats, DAMGO failed to affect significantly forskolin-stimulated adenylyl cyclase. However, in whole brain membranes from naltrexone-treated rats, DAMGO caused a 30% inhibition of forskolin-stimulated adenylyl cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

SO  - J Pharmacol Exp Ther 1993  Oct;267(1):238-244

54

UI  - 9773

AU  - O'Malley SS

AU  - Jaffe AJ

AU  - Chang G

AU  - Schottenfeld RS

AU  - Meyer RE

AU  - Rounsaville B

TI  - Naltrexone and coping skills therapy for alcohol dependence. A controlled study

NT  - 93074284 Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. 06511 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

SO  - Archives of General Psychiatry 1992  Nov;49(11):881-887

55

UI  - 9942

AU  - Parker LA

AU  - Rennie M

TI  - Naltrexone-induced aversions: assessment by place conditioning, taste reactivity, and taste avoidance paradigms

NT  - 92262553 Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, Canada The reinforcing/aversive properties of various doses of naltrexone (0.01, 1, and 10 mg/kg) were assessed in three experiments that employed place conditioning, taste reactivity, and taste avoidance paradigms. Naltrexone produced a place aversion and a taste aversion, but did not produce aversive taste reactivity responses, even at the highest dose (10 mg/kg) tested. This suggests that drugs that produce a place aversion do not necessarily produce a conditional dislike for a flavored solution with which they are paired

SO  - Pharmacol Biochem Behav 1992  Mar;41(3):559-565

56

UI  - 13511

AU  - Volpicelli JR

AU  - Alterman AI

AU  - Hayashida M

AU  - O'Brien CP

AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia

TI  - Naltrexone in the treatment of alcohol dependence88

AB  - 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

SO  - Arch Gen Psychiatry 1992 Nov ;49(11):876-880

57

UI  - 2522

AU  - Kornet M

AU  - Goosen C

AU  - Van-Ree J

TI  - Effect of naltrexone on alcohol consumption during chronic alcohol drinking and after a period of imposed abstinence in free- choice drinking rhesus monkeys

NT  - Studied the effect of naltrexone (NAL) in 8 adult male monkeys, who had about 1 yr experience with alcohol drinking, under 2 conditions: (1) during continuous and concurrent supply of drinking water and 2 ethanol/water solutions (Exp 1) and (2) after 2 days of alcohol abstinence (Exp 2). Each S received 6 doses of NAL; each dose was paired with a placebo injection. Consumption was measured from 1600 hrs to 900 hrs the next morning. In Exp 1, NAL reduced total net ethanol intake in a graded dose-dependent manner. NAL's effect was apparent shortly after injection and lasted until the next day. Consumption of drinking water was reduced only shortly after injection. In Exp 2, reduction of net ethanol intake was restricted to the 1st few hours of reinitiation of alcohol drinking. Consumption of drinking water was not affected. Data indicate that endogenous opioids were involved in chronic alcohol drinking and in drinking after abstinence. (PsycLIT Database Copyright 1992 American Psychological Assn, all rights reserved)

SO  - Psychopharmacology 1991  ;104():367-376

58

UI  - 9924

AU  - Mello NK

TI  - Preclinical evaluation of the effects of buprenorphine, naltrexone and desipramine on cocaine self-administration. [Review]

SO  - NIDA Research Monograph Series 1991  ;105():189-195

59

UI  - 13426

AU  - Kleber HD

AU  - Kosten TR

AU  - Gaspari J

AU  - Topazian M

TI  - Nontolerance to the opioid antagonism of naltrexone205

AB  - Controlled opiate challenges of naltrexone-pretreated human subjects have established that naltrexone is an effective opioid antagonist. However, these challenges have been conducted after relatively acute dosing with naltrexone, and tolerance to this antagonism after chronic treatment is possible. We therefore administered morphine challenges in a double-blind, placebo-controlled design to nine ex-addicts who had been taking naltrexone for a mean of 9.4 months. None of the ex-addicts experienced euphoria; instead, most of these blockaded ex-addicts had a dysphoric histaminelike response to the intravenous morphine. The only physiological change was a slight increase in heart rate. We conclude that tolerance does not develop to the opioid antagonist properties of naltrexone up to as long as 21 months of treatment

SO  - Biol Psychiatry 1985 Jan ;20(1):66-72

60

UI  - 13032

AU  - O'Brien CP

AU  - Childress AR

AU  - McLellan AT

AU  - Ternes J

AU  - Ehrman RN

TI  - Use of naltrexone to extinguish opioid-conditioned responses157

AB  - Opioid use generates many conditioned responses associated with the sights, sounds, smells, and rituals experienced during addiction. Environmental stimuli alone can provoke withdrawal symptoms and contribute to relapses in treated patients. The use of naltrexone in a program designed to progressively extinguish conditioned drug responses is described. Since naltrexone effectively blocks opiate effects at the receptor level, heroin injections produce no euphoria. Unreinforced self-injections diminish the responses learned during the period of drug abuse and protect the patient from rapid readdiction. Patients are confronted with a hierarchical set of drug-related stimuli and taught a muscular relaxation procedure to relieve arousal and discomfort. The continued administration of naltrexone, the self-induced relaxation response, and the repeated presentation of drug-related stimuli result in the eventual diminution or extinction of the arousal properties of the imagery and environmental stimuli associated with addiction

SO  - J Clin Psychiatry 1984 Sep ;45(9 Pt 2):53-56

61

UI  - 14175

AU  - Zukin RS

AU  - Sugarman JR

AU  - Fitz-Syage ML

AU  - Gardner EL

AU  - Zukin SR

AU  - Gintzler AR

TI  - Naltrexone-induced opiate receptor supersensitivity

AB  - Chronic administration of the long-lived narcotic antagonist naltrexone resulted in a marked increase in brain opiate receptors. Similar changes in receptor density were observed for binding of the putative mu agonist [3H]dihydromorphine, the mu antagonist [3H]naloxone, the putative delta ligand [3H]D-Ala2,D-Leu5-enkephalin and [3H]etorphine. In addition, the sensitivity of agonist binding to guanyl nucleotide inhibition increased significantly. In contrast, no such changes in opiate binding were observed following acute administration of naltrexone. The increase in opiate receptor number following chronic naltrexone was highest in the mesolimbic and frontal cortex areas, and lowest in the dorsal hippocampus and periaqueductal gray. These results indicate a degree of plasticity in the opiate receptor system that may correlate with specific functional pathways

SO  - Brain Res 1982 Aug 12 ;245(2):285-292

62

UI  - 19811

AU  - Altshuler HL

AU  - Phillips PE

AU  - Feinhandler DA

TI  - Alteration of ethanol self-administration by naltrexone

SO  - Life Sci 1980 Mar 3 ;26(9):679-688