Naltrexone and cognitive behavioral therapy for the treatment of alcohol dependence: do sex differences exist?

BACKGROUND: Sex differences in regards to pharmacotherapy for alcoholism is a topic of concern following publications suggesting naltrexone, one of the longest approved treatments of alcoholism, is not as effective in women as in men. This study was conducted by combining 2 randomized placebo controlled clinical trials utilizing similar methodologies and personnel in which the data was amalgamated to evaluate sex effects in a reasonable sized sample. METHODS: A total of 211 alcoholics (57 female and 154 male) were randomized to the naltrexone/cognitive behavorial thearpy (CBT) or placebo/CBT arm of the 2 clinical trials analyzed. Baseline variables were examined for differences between sex and treatment groups via ANOVA for continuous variable or chi-squared test for categorical variables. All initial outcome analysis was conducted under an intent-to-treat analysis plan. Effect sizes for naltrexone over placebo were determined by Cohen's D (d). RESULTS: The effect size of naltrexone over placebo for the following outcome variables was similar in men and women [% days abstinent (PDA) d = 0.36, % heavy drinking days (PHDD) d = 0.36, and total standard drinks (TSD) d = 0.36]. Only for men were the differences significant secondary to the larger sample size (PDA p = 0.03; PHDD p = 0.03; TSD p = 0.04). There were a few variables (GGT at week-12 change from baseline to week-12: men d = 0.36, p = 0.05; women d = 0.20, p = 0.45 and drinks per drinking day: men d = 0.36, p = 0.05; women d = 0.28, p = 0.34) where the naltrexone effect size for men was greater than women. In women, naltrexone tended to increase continuous abstinent days before a first drink (women d = 0.46, p = 0.09 and men d = 0.00, p = 0.44). CONCLUSIONS: The effect size of naltrexone over placebo appeared similar in women and men in our hands suggesting the findings of sex differences in naltrexone response might have to do with sample size and/or endpoint drinking variables rather than any inherent pharmacological or biological differences in response.

Alcohol consumption, %CDT, GGT and blood pressure change during alcohol treatment.

AIMS: Blood pressure (BP) changes in alcohol-dependent individuals during a 12-week alcohol relapse prevention study were examined in light of drinking status and biomarkers of alcohol consumption [carbohydrate-deficient transferrin (%CDT) and gamma-glutamyl transpeptidase (GGT)]. METHODS: Of 160 randomized alcoholic individuals, 120 who had hypertension and in whom daily drinking data was available, at 6 and 12 weeks of treatment were included. The impact of alcohol consumption on change in systolic BP (SBP) and diastolic BP (DBP) was examined. Further analysis determined the relationship between BP and alcohol-use biomarkers. RESULTS: A significant effect of complete abstinence on both SBP (-10 mmHg; P = 0.003) and DBP (-7 mmHg; P = 0.001) when compared to any drinking (SBP and DBP = -1 mmHg) was observed. At week 12, participants with a positive %CDT (> or =2.6) had 7 mmHg greater SBP (P = 0.01) and DBP (P < 0.001) than those with negative %CDT. Participants with positive GGT (> or =50 IU) had 10 mmHg greater SBP (P = 0.12) and 9 mmHg greater DBP (P = 0.03) than those with negative GGT. The percent change in SBP was correlated with percent change in %CDT (P = 0.003) but not GGT (P = ns). The percent change in DBP was correlated with both percent change in %CDT (P < 0.0001) and GGT (P = 0.03). CONCLUSIONS: Abstinence from alcohol significantly decreased the BP and a positive relationship between BP and both alcohol-use biomarkers was illustrated. Since %CDT is more specific than GGT for heavy alcohol consumption, clinicians may monitor the role of alcohol in hypertension using %CDT as a supplemental aid, providing an objective assessment of drinking to influence BP treatment decisions.

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

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.

Neuropsychological performance deficits in adults with attention deficit/hyperactivity disorder.

Neuropsychological deficits in children diagnosed with attention deficit/hyperactivity disorder (ADHD) have been well documented utilizing various neuropsychological tests. Only recently has research begun to examine if similar deficits are present in adults with ADHD. A neuropsychological testing battery was constructed that assessed verbal learning and memory, psychomotor speed, and sustained attention--all demonstrated to be deficient in individuals with ADHD. Fifty-six self-referred nonmedicated adults with a DSM-IV diagnosis of ADHD and 38 normal comparison adults participated. ADHD adults demonstrated verbal and nonverbal memory deficits and decreased psychomotor speed compared to normal controls. Differences between ADHD and normal adults were not documented on traditional measures of executive functioning. A pattern of results emerged whereby ADHD adults' performance, particularly with regard to psychomotor speed, became more impaired as task complexity increased. This study's results largely corroborate similar neuropsychological testing results in ADHD children and recent ADHD adult findings, and support a frontal lobe dysfunction hypothesis of ADHD.

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

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.

Factor structure and predictive validity of the Obsessive Compulsive Drinking Scale.

BACKGROUND: The Obsessive Compulsive Drinking Scale (OCDS) is a 14-item, self-report instrument developed to measure obsessive thoughts about alcohol use and compulsive behaviors toward drinking. The objective of this study was to ascertain the factor structure underlying responses to the OCDS, and to further assess whether subscale scores derived from this structure were distinctive, internally consistent, predictive of future drinking, and able to differentiate between patients receiving naltrexone versus placebo in a controlled alcoholism treatment trial. METHODS: OCDS data were collected from a total of 132 alcohol-dependent subjects at up to 15 assessment points during the study. Interitem correlations were pooled across assessment periods, and an iterated principal axis factor analysis with oblique promax rotation was performed. The factor analysis suggested that three primary factors could parsimoniously account for the common variance in item responses. Subscale scores were formed by summing responses to the most salient items on each factor. RESULTS: The three common factors were interpreted as "resistance/control impairment," "obsession," and "interference." The subscale scores corresponding to these three factors were internally consistent, and their correlation with other baseline measures of alcohol use and severity suggested that they were distinct. Scores on each subscale reliably distinguished between subjects who remained abstinent, exhibited "slip" drinking, or relapsed to heavy drinking during the 12 weeks of active treatment. Additionally, scores on the resistance/control impairment subscale distinguished between those patients receiving treatment with naltrexone or placebo. Scores from each subscale also were able to predict the hazard for heavy drinking in the following week of treatment. CONCLUSIONS: The three OCDS factors are easily estimated with the summated scoring approach, and the resulting subscales appear to be internally consistent and distinctive. Moreover, the group differentiation capability and predictive utility of the subscale scores suggest that they might be useful as either predictor or outcome variables in alcoholism treatment trials. The duration of time for which a given OCDS assessment maintains its predictive utility awaits further confirmation.

The relationship of cognitive functioning to amount of recent and lifetime alcohol consumption in outpatient alcoholics.

Previous investigations of the relationship between drinking patterns and cognitive functioning have generally studied severely alcoholic patients, in whom the neurocognitive effects of alcohol consumption can be obscured by other medical or psychosocial factors. In the present study, cognitive functioning was examined after a minimum of 4 days of abstinence in 69 mildly to moderately alcohol-dependent outpatients without comorbid psychiatric, neurologic, or systemic medical illness. Circumscribed decrements in reaction time and verbal memory were associated with higher amounts of alcohol consumption in the 90 days prior to enrollment in the study, and amount of recent consumption was correlated with scores on numerous cognitive tests. In contrast, longer drinking history was not associated with poorer performance on any neuropsychological measures. Thus, in this group of high-functioning, mildly to moderately alcohol-dependent outpatients, mild cognitive deficits were related to the amount of recent, but not lifetime, alcohol consumption.

Further validation of the Obsessive-Compulsive Drinking Scale (OCDS). Relationship to alcoholism severity.

The authors administered the Obsessive-Compulsive Drinking Scale (OCDS), a self-rated questionnaire that quantifies some cognitive and behavioral dimensions of "craving" for alcohol, to 124 alcohol-dependent subjects in three pharmacological treatment studies. The OCDS total scores had significant correlations with both the Alcohol Dependence Scale (r = 0.42; P < 0.0001) and the alcohol subscale of the Addiction Severity Index (r = 0.44; P < 0.0001). Previous alcoholism treatment was associated with higher OCDS Total and Obsessive subscale scores. These data support the congruent validity of the OCDS with previously well established measures of alcohol dependence severity and suggest that this measurement of craving may help in formulating appropriate treatment plans for alcoholic patients.

The obsessive compulsive drinking scale: A new method of assessing outcome in alcoholism treatment studies.

BACKGROUND: the 14-item Obsessive Compulsive Drinking Scale (OCDS) is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol "craving". This study validated further its utility as an alcoholism severity and treatment outcome instrument. METHODS: Alcoholism severity and analogue craving scales were administered at baseline, and the OCDS was given at baseline and weekly to 41 alcohol-dependent individuals who participated in a 12-week pharmacologic and cognitive-behavioral treatment trial. Repeated-measures analysis of variance was used to examine group differences in the OCDS scores of those individuals who remained abstinent or drank during the trial. RESULTS: At baseline, the OCDS was correlated with the alcohol composite score of the addiction severity index (r=.48), the alcohol dependence scale (r=.42), the analogue craving measures (range r=.40 to .57), and prestudy alcohol consumption (r=.60). Most importantly the OCDS total and subscale scores were significantly different between individuals who had relapse drinking, who had "slip" drinking, and who remained abstinent, with relapsers showing the highest scores. CONCLUSIONS: The OCDS scores appear to be sensitive to alcoholism severity and change during abstinence and relapse drinking. Since the shared variance with analogue craving measures is only about 20% to 30%, it appears to be measuring a largely independent dimension of alcohol dependence. Its ease of use (5 minutes per self-rating), reliability, validity, and analytic capabilities support its utility as a tool to measure severity and improvement during alcoholism treatment trials.

Symptoms of anxiety in inpatient alcoholics with and without DSM-III-R anxiety diagnoses.

Self- and observer-rating scales were administered to alcohol-dependent inpatients during acute withdrawal and regularly for 3 weeks. Following a structured diagnostic interview (SCID) at the end of the 3rd week of hospitalization, subjects were divided into two groups: a dual-diagnosed group (alcohol dependence and anxiety disorder) and an alcohol-only group (no other current Axis I diagnosis). The results demonstrated that the dual-diagnosed subjects experienced higher anxiety levels during and after acute alcohol withdrawal. All rating scales (i.e., Sheehan Patient Rated Anxiety Scale, Spielberger State Anxiety Inventory, Zung Rating Scale for Anxiety, and Hamilton Rating Scale for Anxiety) were analyzed to obtain the best combination of sensitivity and specificity. Taken together, the results indicate that it may be possible to identify alcoholics who require additional psychiatric evaluation early in treatment. This would allow a treatment plan which could be used to address both psychiatric and substance abuse problems.

Psychosocial and psychopathology differences in hospitalized male and female cocaine abusers: a retrospective chart review.

While considerable amounts of psychological and pharmacological data have been collected on male substance abusers in public treatment facilities, relatively little information is available about the psychosocial characteristics of men in private treatment settings and of women presenting for substance abuse treatment. The present study reviewed the records of 100 male and female cocaine abusers admitted to a private substance abuse treatment program between 1987 and 1989. Patterns of cocaine use and levels of impairment were found to be similar for men and women, with male cocaine abusers more likely to abuse additional substances. Male cocaine abusers were employed more frequently than women and held higher status jobs despite equivalent levels of education. Female cocaine abusers were more likely to be diagnosed with concurrent psychiatric disorders and were more likely to report family histories of substance abuse. Both groups produced elevations on MMPI scales indicating depression, anxiety, paranoid features, and acting-out tendencies. These data suggest that while male and female cocaine abusers show similarities on some measures, there are significant gender differences that may have implications for both research and treatment.