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