IN the course of researching possible drug treatments I came across these studies. I post some of them here so you can make up your own mind about it. I think all/most of them are Naltrexone combined with drinking. They are all pretty recent (2008-2010)
Am J Psychiatry 167:10, October 2010
Naltrexone Effects in Patients With Dementia
TO THE EDITOR: In their recent articles published in the Journal,
Blazer and Wu (1) and Mathews and Oslin (2) have drawn
attention to alcohol use among the elderly. Furthermore, a
recent Treatment in Psychiatry article, by Johnson (3), highlighted
pharmacologic interventions for alcoholism, where naltrexone was suggested in two out of three cases, including
for a 66-year-old patient. To add to the discussion of naltrexone
use in the elderly, three cases are presented suggesting
potential benefi ts of naltrexone for the treatment of alcoholism
complicating dementia.
?Mr. S? was an 84-year-old man with long-standing
bipolar I disorder and alcoholism. He had developed dementia
as a result of Alzheimer?s disease. His persistent
alcoholism included consumption of up to one-fi fth of
whiskey daily, which led to bizarre and dangerous behaviors.
He began naltrexone (50 mg daily), which resulted
in reduced interest in alcohol within the fi rst week. This
improvement was sustained even after treatment was discontinued
6 months later.
?Ms. A? was an 86-year-old woman with frontotemporal
dementia who repeatedly drank scotch to intoxication,
resulting in frequent falls. Bottles of liquor were stashed
throughout her house, and she became acutely agitated
if she was prevented from buying more. While receiving
treatment with naltrexone (50 mg daily), the forcefulness
of her alcohol-seeking behavior abated, and after 3 weeks
she discontinued drinking altogether. Naltrexone was continued
for a full year, with continued sobriety.
?Mr. C? was a 68-year-old man with Wernicke-Korsakoff
syndrome. He was able to live independently with
a supportive landlord, but placement in a secure facility
was considered after several hospitalizations resulted
from his drinking to unconsciousness. While receiving
treatment with naltrexone (50 mg), he discontinued frequenting
local bars and was able to continue living in his
familiar neighborhood.
Published data on the use of naltrexone in the elderly is not
available, but it is of note that alcohol abuse ended promptly
in these three cases. Clinical benefi t was signifi cant given that
these patients continued to live in their communities with
a reduction in caregiver stress and reduced harmful events
such as falls. The benefi cial response observed in these cases
is unlikely the result of a placebo response, and the prompt
reduction in alcohol craving probably represents a true neuropharmacologic
effect of reducing alcohol-related euphoria
and undermining alcohol-seeking behavior. While progression
of dementia may have contributed to reduced addictive
behaviors, the prompt reduction in drinking does suggest
that anticraving medications may have a role for elderly
patients.
Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus.
2010 Jan 1; Vol. 67 (1), pp. 78-80.
The role of a nonsynonymous A118G polymorphism of the human micro-opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of naltrexone remains controversial. A functionally equivalent OPRM1 C77G polymorphism in rhesus macaques allows this to be addressed under controlled experimental conditions. METHODS: Twenty-one rhesus macaques (13 female rhesus macaques, 8 male rhesus macaques) were genotyped for OPRM1 C77G and studied during 1-hour sessions for preference between an aspartame-sweetened alcohol solution (8.4% vol/vol) and a nonalcoholic control fluid in a baseline session followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced within-subject design. RESULTS: Mixed-model analysis of variance controlling for baseline and sex showed a highly significant (p = .003) interaction between genotype and treatment. Post hoc analysis showed that vehicle-treated 77G carriers had markedly higher alcohol preference than 77C homozygous subjects (p = .001). Following naltrexone administration, 77G carriers decreased their preference (p = .002) and no longer differed from 77C homozygous subjects. In contrast, the latter group was unaffected by treatment and, in fact, showed a trend-level increase of preference following naltrexone. CONCLUSIONS: These results support a critical pharmacogenetic role of OPRM1 variation for therapeutic efficacy of naltrexone.
Efficacy and tolerability of naltrexone in the management of alcohol dependence.
Current Pharmaceutical Design [Curr Pharm Des] 2010; Vol. 16 (19), pp. 2091-7.
Naltrexone, a broad opioid-receptor antagonist, was the first medication since disulfiram to be approved by the United States of America Food and Drug Administration for the treatment of alcohol dependence. In the initial clinical trials in the early 1990s, oral naltrexone, 50 mg, was shown to significantly reduce the risk of relapsing to heavy drinking compared to placebo. These early trials were followed by other trials throughout the world such that by 2010 about 4,000 individuals had been studied. Meta-analyses of these trials revealed that oral naltrexone is effective in reducing relapse to heavy drinking but less effective in enhancing abstinence. The effect size is modest, in the .15 to .2 range, which has impacted the adoption of naltrexone use by clinicians. Intramuscular versions of naltrexone active for one month have also shown efficacy. The tolerability of naltrexone is reasonable with the most common side-effect being nausea. Hepatotoxicity with naltrexone has not emerged as a clinical problem at the standard 50 mg dose though at higher doses hepatoxicity is of concern. The length of treatment with naltrexone has not been well studied though many clinicians recommend one year of treatment. Efforts are underway to identify predictors of naltrexone response but, to date, no predictor has achieved clinical utility. It is anticipated that the role of naltrexone and other opioid antagonists in the treatment of alcohol dependence will continue to be refined and that this class of medications will come to be seen as an important option in the clinical care of the patient with alcohol dependence.
A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence.
Alcoholism, Clinical And Experimental Research [Alcohol Clin Exp Res] 2009 Nov; Vol. 33 (11), pp. 1863-9. Date of Electronic Publication: 2009 Aug 10.
BACKGROUND: Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence. METHODS: Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed. RESULTS: The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence. CONCLUSIONS: Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.
Targeted naltrexone for problem drinkers.
Authors:
Kranzler HR; Tennen H; Armeli S; Chan G; Covault J; Arias A; Oncken C
This study aimed to replicate and extend prior research showing that the targeted use of naltrexone is a useful strategy to reduce heavy drinking. We compared the effects of naltrexone with those of placebo in a sample of 163 individuals (58.3% male) whose goal was to reduce their drinking to safe limits. Patients received study medication (ie, naltrexone 50 mg or placebo) and were instructed to use it daily or targeted to situations identified by them as being high risk for heavy drinking. An interactive voice response system was used to obtain daily reports of drinking and medication use during the 12-week trial. Analyses were conducted using hierarchical linear modeling, with sex as a potential moderator variable. On the primary outcome measure, mean drinks per day, at week 12, men in the targeted naltrexone group drank significantly less than patients in the other groups did. On a secondary outcome measure, drinks per drinking day, during week 12, the targeted naltrexone group drank significantly less than the other groups did, with no moderating effect of sex. These results support the use of a targeted approach to reduce drinking among heavy drinkers, particularly men, but argue for the use of additional strategies or more efficacious medications than naltrexone to increase the effects of such an intervention.
Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients.
Pettinati HM; Gastfriend DR; Dong Q; Kranzler HR; O'Malley SS
BACKGROUND: Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation for the treatment of alcohol dependence previously shown to reduce drinking and heavy drinking relative to placebo (Garbutt et al., 2005). A 24-week, randomized, double-blind, placebo-controlled study established the efficacy and safety of XR-NTX in this patient population. In this report, the effect of XR-NTX on quality of life (QOL) was examined. METHODS: Alcohol-dependent patients were randomly assigned to receive XR-NTX 380 mg (N = 205), XR-NTX 190 mg (N = 210), or placebo (N = 209), combined with a standardized psychosocial intervention. QOL was assessed using the Medical Outcomes Study 36-item short-form health survey, administered at baseline and at 4-week intervals during 24 weeks of treatment. RESULTS: Compared with U.S. population norms, patients showed initial impairment in the health-related QOL domains of mental health, social functioning, and problems with work or other daily activities due to emotional problems. Adherence to all 6 injections was 65% for XR-NTX 190 mg, 63% for XR-NTX 380 mg, and 64% for placebo. Generalized estimating equations analyses using an intention-to-treat sample revealed that XR-NTX 380 mg was associated with significantly greater improvements from baseline in mental health (p = 0.0496), social functioning (p = 0.010), general health (p = 0.048), and physical functioning (p = 0.028), compared with placebo. Linear regression analyses revealed that reductions from baseline in drinking (percentage of drinking days and percentage of heavy drinking days in the last 30 days) were significantly (p < 0.05) correlated with improvements in quality of life. CONCLUSION: Extended-release naltrexone 380 mg in combination with psychosocial intervention was associated with improvements in QOL, specifically in the domains of mental health, social functioning, general health, and physical functioning.
Effects of alcoholism typology on response to naltrexone in the COMBINE study.
Bogenschutz MP; Scott Tonigan J; Pettinati HM
BACKGROUND: This study investigated whether subgroups of alcohol-dependent patients responded differently to naltrexone versus placebo in the NIAAA COMBINE study. In particular, the A versus B and the Early Onset versus Late Onset typologies were examined. Relative to Type A alcoholics, Type B alcoholics are characterized by greater severity, earlier onset, stronger family history, more childhood risk factors (e.g., conduct disorder), and greater frequency of comorbid psychiatric and substance use disorders. METHODS: COMBINE study participants were categorized as Type A or Type B using k-means cluster analysis and variables from 5 domains that have been shown to replicate the original Babor typology efficiently. Early Onset was defined as alcohol dependence beginning before age 25. For the planned analyses, the sample was reduced to the 618 participants receiving naltrexone alone or placebo, either with medical management (MM) alone or with MM plus the Combined Behavioral Intervention (CBI). The a priori primary outcome was percent heavy drinking days during treatment in the groups receiving MM without CBI. RESULTS: Among those receiving MM without CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo, whereas medication condition did not influence outcomes significantly in the Type Bs. Age of onset was not significantly related to outcome. For those receiving CBI, no significant effects were found for either typology. CONCLUSIONS: In this sample, the beneficial effects of opioid antagonism were limited to Type A alcoholics receiving treatment in a MM model. Future studies should investigate the relationship between clinically relevant genotypes, phenotypes such as typologies, and treatment response. More work is also needed to develop practical algorithms for phenotypic assignment.
Comparing topiramate with naltrexone in the treatment of alcohol dependence.
Baltieri DA; Dar? FR; Ribeiro PL; de Andrade AG
AIM: To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence. DESIGN: The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of S?o Paulo, Brazil. SAMPLE: A total of 155 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. METHODS: After a 1-week detoxification period, patients were assigned randomly to receive topiramate (induction to 300 mg/day), naltrexone (50 mg/day) or placebo. MEASUREMENTS: Time to first relapse (consumption of >60 g ethyl alcohol), cumulative abstinence duration and weeks of heavy drinking. FINDINGS: In intention-to-treat analyses, topiramate was statistically superior to placebo on a number of measures including time to first relapse (7.8 versus 5.0 weeks), cumulative abstinence duration (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9) and percentage of subjects abstinent at 4 weeks (67.3 versus 42.6) and 8 weeks (61.5 versus 31.5), but not 12 weeks (46.2 versus 27.8). RESULTS: remained significant after controlling for Alcoholics Anonymous attendance, which was higher in topiramate than in other groups. There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups, but naltrexone showed trends toward inferior outcomes when compared to topiramate. CONCLUSIONS: The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism. Suggestive evidence was also obtained for superiority of topiramate versus naltrexone, but this needs to be verified in future research with larger sample sizes.
Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes.
R?sner S; Leucht S; Lehert P; Soyka M
Two pharmacological agents have repeatedly been shown to be efficacious for relapse prevention in alcohol dependence: The putative glutamate-antagonist acamprosate and the opioid-antagonist naltrexone. Clinical evidence for both drugs is based on various outcome criteria. Whereas for acamprosate primarily abstinence maintenance has been demonstrated, studies with naltrexone have mostly emphasised the prevention of heavy drinking. The remaining effects of both drugs are not always reported; accordingly the corresponding database is fragmentary. Thus, the primary objective of the present meta-analysis was to complete the efficacy profiles for acamprosate and naltrexone and to compare them with each other. Unreported results, requested from the study investigators and the drug manufacturers, were integrated in the computation of effect sizes. For the meta-analysis, emphasis was placed on the conceptual distinction between having a first drink and returning to heavy drinking. Naltrexone was found to have a significant effect on the maintenance of abstinence as well as the prevention of heavy drinking. Acamprosate was shown only to support abstinence; it did not influence alcohol consumption after the first drink. When the efficacy profiles of the two drugs were compared, acamprosate was found to be more effective in preventing a lapse, whereas naltrexone was better in preventing a lapse from becoming a relapse. The superiority of either one drug or over the other one cannot be determined as a general rule, it rather depends on the therapeutic target. Benefits in the treatment of alcohol dependence might be optimized by matching the efficacy profiles of specific antidipsotropics with the motivational status of alcohol-dependent patients.
Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking.
Krishnan-Sarin S; Krystal JH; Shi J; Pittman B; O'Malley SS
BACKGROUND: The purpose of this study was to examine the interactive effects of family history of alcoholism (FH+, FH-) and naltrexone dose (0, 50, 100 mg/day) on alcohol drinking. METHODS: Ninety-two, non-treatment-seeking alcohol-dependent participants received naltrexone daily for 6 days. On the 6th day, they participated in a laboratory paradigm involving exposure to a priming dose of alcohol followed by a 2-hour drinking period in which they made choices between consuming alcoholic drinks and receiving money. RESULTS: Total number of drinks consumed during the drinking period was significantly decreased by the 100-mg dose of naltrexone in FH+ drinkers. Secondary analyses in male drinkers (n = 70) indicated that 100 mg of naltrexone significantly decreased drinking in FH+ participants and increased drinking in FH- drinkers. CONCLUSIONS: These results suggest that family history of alcoholism might be a significant clinical predictor of response to naltrexone and that FH+ men are more likely to benefit from naltrexone therapy for alcohol drinking.
Am J Psychiatry 167:10, October 2010
Naltrexone Effects in Patients With Dementia
TO THE EDITOR: In their recent articles published in the Journal,
Blazer and Wu (1) and Mathews and Oslin (2) have drawn
attention to alcohol use among the elderly. Furthermore, a
recent Treatment in Psychiatry article, by Johnson (3), highlighted
pharmacologic interventions for alcoholism, where naltrexone was suggested in two out of three cases, including
for a 66-year-old patient. To add to the discussion of naltrexone
use in the elderly, three cases are presented suggesting
potential benefi ts of naltrexone for the treatment of alcoholism
complicating dementia.
?Mr. S? was an 84-year-old man with long-standing
bipolar I disorder and alcoholism. He had developed dementia
as a result of Alzheimer?s disease. His persistent
alcoholism included consumption of up to one-fi fth of
whiskey daily, which led to bizarre and dangerous behaviors.
He began naltrexone (50 mg daily), which resulted
in reduced interest in alcohol within the fi rst week. This
improvement was sustained even after treatment was discontinued
6 months later.
?Ms. A? was an 86-year-old woman with frontotemporal
dementia who repeatedly drank scotch to intoxication,
resulting in frequent falls. Bottles of liquor were stashed
throughout her house, and she became acutely agitated
if she was prevented from buying more. While receiving
treatment with naltrexone (50 mg daily), the forcefulness
of her alcohol-seeking behavior abated, and after 3 weeks
she discontinued drinking altogether. Naltrexone was continued
for a full year, with continued sobriety.
?Mr. C? was a 68-year-old man with Wernicke-Korsakoff
syndrome. He was able to live independently with
a supportive landlord, but placement in a secure facility
was considered after several hospitalizations resulted
from his drinking to unconsciousness. While receiving
treatment with naltrexone (50 mg), he discontinued frequenting
local bars and was able to continue living in his
familiar neighborhood.
Published data on the use of naltrexone in the elderly is not
available, but it is of note that alcohol abuse ended promptly
in these three cases. Clinical benefi t was signifi cant given that
these patients continued to live in their communities with
a reduction in caregiver stress and reduced harmful events
such as falls. The benefi cial response observed in these cases
is unlikely the result of a placebo response, and the prompt
reduction in alcohol craving probably represents a true neuropharmacologic
effect of reducing alcohol-related euphoria
and undermining alcohol-seeking behavior. While progression
of dementia may have contributed to reduced addictive
behaviors, the prompt reduction in drinking does suggest
that anticraving medications may have a role for elderly
patients.
Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus.
2010 Jan 1; Vol. 67 (1), pp. 78-80.
The role of a nonsynonymous A118G polymorphism of the human micro-opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of naltrexone remains controversial. A functionally equivalent OPRM1 C77G polymorphism in rhesus macaques allows this to be addressed under controlled experimental conditions. METHODS: Twenty-one rhesus macaques (13 female rhesus macaques, 8 male rhesus macaques) were genotyped for OPRM1 C77G and studied during 1-hour sessions for preference between an aspartame-sweetened alcohol solution (8.4% vol/vol) and a nonalcoholic control fluid in a baseline session followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced within-subject design. RESULTS: Mixed-model analysis of variance controlling for baseline and sex showed a highly significant (p = .003) interaction between genotype and treatment. Post hoc analysis showed that vehicle-treated 77G carriers had markedly higher alcohol preference than 77C homozygous subjects (p = .001). Following naltrexone administration, 77G carriers decreased their preference (p = .002) and no longer differed from 77C homozygous subjects. In contrast, the latter group was unaffected by treatment and, in fact, showed a trend-level increase of preference following naltrexone. CONCLUSIONS: These results support a critical pharmacogenetic role of OPRM1 variation for therapeutic efficacy of naltrexone.
Efficacy and tolerability of naltrexone in the management of alcohol dependence.
Current Pharmaceutical Design [Curr Pharm Des] 2010; Vol. 16 (19), pp. 2091-7.
Naltrexone, a broad opioid-receptor antagonist, was the first medication since disulfiram to be approved by the United States of America Food and Drug Administration for the treatment of alcohol dependence. In the initial clinical trials in the early 1990s, oral naltrexone, 50 mg, was shown to significantly reduce the risk of relapsing to heavy drinking compared to placebo. These early trials were followed by other trials throughout the world such that by 2010 about 4,000 individuals had been studied. Meta-analyses of these trials revealed that oral naltrexone is effective in reducing relapse to heavy drinking but less effective in enhancing abstinence. The effect size is modest, in the .15 to .2 range, which has impacted the adoption of naltrexone use by clinicians. Intramuscular versions of naltrexone active for one month have also shown efficacy. The tolerability of naltrexone is reasonable with the most common side-effect being nausea. Hepatotoxicity with naltrexone has not emerged as a clinical problem at the standard 50 mg dose though at higher doses hepatoxicity is of concern. The length of treatment with naltrexone has not been well studied though many clinicians recommend one year of treatment. Efforts are underway to identify predictors of naltrexone response but, to date, no predictor has achieved clinical utility. It is anticipated that the role of naltrexone and other opioid antagonists in the treatment of alcohol dependence will continue to be refined and that this class of medications will come to be seen as an important option in the clinical care of the patient with alcohol dependence.
A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence.
Alcoholism, Clinical And Experimental Research [Alcohol Clin Exp Res] 2009 Nov; Vol. 33 (11), pp. 1863-9. Date of Electronic Publication: 2009 Aug 10.
BACKGROUND: Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence. METHODS: Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed. RESULTS: The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence. CONCLUSIONS: Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.
Targeted naltrexone for problem drinkers.
Authors:
Kranzler HR; Tennen H; Armeli S; Chan G; Covault J; Arias A; Oncken C
This study aimed to replicate and extend prior research showing that the targeted use of naltrexone is a useful strategy to reduce heavy drinking. We compared the effects of naltrexone with those of placebo in a sample of 163 individuals (58.3% male) whose goal was to reduce their drinking to safe limits. Patients received study medication (ie, naltrexone 50 mg or placebo) and were instructed to use it daily or targeted to situations identified by them as being high risk for heavy drinking. An interactive voice response system was used to obtain daily reports of drinking and medication use during the 12-week trial. Analyses were conducted using hierarchical linear modeling, with sex as a potential moderator variable. On the primary outcome measure, mean drinks per day, at week 12, men in the targeted naltrexone group drank significantly less than patients in the other groups did. On a secondary outcome measure, drinks per drinking day, during week 12, the targeted naltrexone group drank significantly less than the other groups did, with no moderating effect of sex. These results support the use of a targeted approach to reduce drinking among heavy drinkers, particularly men, but argue for the use of additional strategies or more efficacious medications than naltrexone to increase the effects of such an intervention.
Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients.
Pettinati HM; Gastfriend DR; Dong Q; Kranzler HR; O'Malley SS
BACKGROUND: Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation for the treatment of alcohol dependence previously shown to reduce drinking and heavy drinking relative to placebo (Garbutt et al., 2005). A 24-week, randomized, double-blind, placebo-controlled study established the efficacy and safety of XR-NTX in this patient population. In this report, the effect of XR-NTX on quality of life (QOL) was examined. METHODS: Alcohol-dependent patients were randomly assigned to receive XR-NTX 380 mg (N = 205), XR-NTX 190 mg (N = 210), or placebo (N = 209), combined with a standardized psychosocial intervention. QOL was assessed using the Medical Outcomes Study 36-item short-form health survey, administered at baseline and at 4-week intervals during 24 weeks of treatment. RESULTS: Compared with U.S. population norms, patients showed initial impairment in the health-related QOL domains of mental health, social functioning, and problems with work or other daily activities due to emotional problems. Adherence to all 6 injections was 65% for XR-NTX 190 mg, 63% for XR-NTX 380 mg, and 64% for placebo. Generalized estimating equations analyses using an intention-to-treat sample revealed that XR-NTX 380 mg was associated with significantly greater improvements from baseline in mental health (p = 0.0496), social functioning (p = 0.010), general health (p = 0.048), and physical functioning (p = 0.028), compared with placebo. Linear regression analyses revealed that reductions from baseline in drinking (percentage of drinking days and percentage of heavy drinking days in the last 30 days) were significantly (p < 0.05) correlated with improvements in quality of life. CONCLUSION: Extended-release naltrexone 380 mg in combination with psychosocial intervention was associated with improvements in QOL, specifically in the domains of mental health, social functioning, general health, and physical functioning.
Effects of alcoholism typology on response to naltrexone in the COMBINE study.
Bogenschutz MP; Scott Tonigan J; Pettinati HM
BACKGROUND: This study investigated whether subgroups of alcohol-dependent patients responded differently to naltrexone versus placebo in the NIAAA COMBINE study. In particular, the A versus B and the Early Onset versus Late Onset typologies were examined. Relative to Type A alcoholics, Type B alcoholics are characterized by greater severity, earlier onset, stronger family history, more childhood risk factors (e.g., conduct disorder), and greater frequency of comorbid psychiatric and substance use disorders. METHODS: COMBINE study participants were categorized as Type A or Type B using k-means cluster analysis and variables from 5 domains that have been shown to replicate the original Babor typology efficiently. Early Onset was defined as alcohol dependence beginning before age 25. For the planned analyses, the sample was reduced to the 618 participants receiving naltrexone alone or placebo, either with medical management (MM) alone or with MM plus the Combined Behavioral Intervention (CBI). The a priori primary outcome was percent heavy drinking days during treatment in the groups receiving MM without CBI. RESULTS: Among those receiving MM without CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo, whereas medication condition did not influence outcomes significantly in the Type Bs. Age of onset was not significantly related to outcome. For those receiving CBI, no significant effects were found for either typology. CONCLUSIONS: In this sample, the beneficial effects of opioid antagonism were limited to Type A alcoholics receiving treatment in a MM model. Future studies should investigate the relationship between clinically relevant genotypes, phenotypes such as typologies, and treatment response. More work is also needed to develop practical algorithms for phenotypic assignment.
Comparing topiramate with naltrexone in the treatment of alcohol dependence.
Baltieri DA; Dar? FR; Ribeiro PL; de Andrade AG
AIM: To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence. DESIGN: The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of S?o Paulo, Brazil. SAMPLE: A total of 155 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. METHODS: After a 1-week detoxification period, patients were assigned randomly to receive topiramate (induction to 300 mg/day), naltrexone (50 mg/day) or placebo. MEASUREMENTS: Time to first relapse (consumption of >60 g ethyl alcohol), cumulative abstinence duration and weeks of heavy drinking. FINDINGS: In intention-to-treat analyses, topiramate was statistically superior to placebo on a number of measures including time to first relapse (7.8 versus 5.0 weeks), cumulative abstinence duration (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9) and percentage of subjects abstinent at 4 weeks (67.3 versus 42.6) and 8 weeks (61.5 versus 31.5), but not 12 weeks (46.2 versus 27.8). RESULTS: remained significant after controlling for Alcoholics Anonymous attendance, which was higher in topiramate than in other groups. There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups, but naltrexone showed trends toward inferior outcomes when compared to topiramate. CONCLUSIONS: The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism. Suggestive evidence was also obtained for superiority of topiramate versus naltrexone, but this needs to be verified in future research with larger sample sizes.
Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes.
R?sner S; Leucht S; Lehert P; Soyka M
Two pharmacological agents have repeatedly been shown to be efficacious for relapse prevention in alcohol dependence: The putative glutamate-antagonist acamprosate and the opioid-antagonist naltrexone. Clinical evidence for both drugs is based on various outcome criteria. Whereas for acamprosate primarily abstinence maintenance has been demonstrated, studies with naltrexone have mostly emphasised the prevention of heavy drinking. The remaining effects of both drugs are not always reported; accordingly the corresponding database is fragmentary. Thus, the primary objective of the present meta-analysis was to complete the efficacy profiles for acamprosate and naltrexone and to compare them with each other. Unreported results, requested from the study investigators and the drug manufacturers, were integrated in the computation of effect sizes. For the meta-analysis, emphasis was placed on the conceptual distinction between having a first drink and returning to heavy drinking. Naltrexone was found to have a significant effect on the maintenance of abstinence as well as the prevention of heavy drinking. Acamprosate was shown only to support abstinence; it did not influence alcohol consumption after the first drink. When the efficacy profiles of the two drugs were compared, acamprosate was found to be more effective in preventing a lapse, whereas naltrexone was better in preventing a lapse from becoming a relapse. The superiority of either one drug or over the other one cannot be determined as a general rule, it rather depends on the therapeutic target. Benefits in the treatment of alcohol dependence might be optimized by matching the efficacy profiles of specific antidipsotropics with the motivational status of alcohol-dependent patients.
Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking.
Krishnan-Sarin S; Krystal JH; Shi J; Pittman B; O'Malley SS
BACKGROUND: The purpose of this study was to examine the interactive effects of family history of alcoholism (FH+, FH-) and naltrexone dose (0, 50, 100 mg/day) on alcohol drinking. METHODS: Ninety-two, non-treatment-seeking alcohol-dependent participants received naltrexone daily for 6 days. On the 6th day, they participated in a laboratory paradigm involving exposure to a priming dose of alcohol followed by a 2-hour drinking period in which they made choices between consuming alcoholic drinks and receiving money. RESULTS: Total number of drinks consumed during the drinking period was significantly decreased by the 100-mg dose of naltrexone in FH+ drinkers. Secondary analyses in male drinkers (n = 70) indicated that 100 mg of naltrexone significantly decreased drinking in FH+ participants and increased drinking in FH- drinkers. CONCLUSIONS: These results suggest that family history of alcoholism might be a significant clinical predictor of response to naltrexone and that FH+ men are more likely to benefit from naltrexone therapy for alcohol drinking.