Compliance with Treatment and Follow-up Protocols in Project MATCH: Predictors and Relationship to Outcome

Treatment and follow-up session attendance data from Project MATCH, a multisite clinical trial investigating patient-treatment matching, were analyzed to study compliance. High rates of compliance to both therapy and research protocols were achieved, enhancing treatment integrity and data quality. Strong baseline predictors of compliance did not emerge, and the small relationships found were consistent with reports from previous studies. Attendance at therapy sessions was moderately correlated with research follow-up participation. Treatment compliance predicted drinking outcome, underscoring the importance of retaining patients in treatment. Future studies should examine the associations between compliance and structural features of the treatment environment, treatment delivery, and context-features that are often under the control of the clinician/investigator.     

Fluoxetine Treatment Seems to Reduce the Beneficial Effects of Cognitive-Behavioral Therapy in Type B Alcoholics

Objective : The aim of this study was to test the hypothesis that, because of abnormalities in serotonergic neurotransmission that may underlie craving and impulsive behavior, fluoxetine treatment differentially affects drinking among type B alcoholics, who are characterized by high levels of both premorbid vulnerability and alcohol-related problems. Methods : Using a k -means clustering procedure, alcohol-dependent subjects from a placebo-controlled trial of fluoxetine were grouped into low-risk/severity (type A n = 60) and highrisk/severity (type B: n = 35) groups. Multivariate analysis of covariance (with pretreatment measures as covariates) evaluated the effects of Alcoholic Subtype, Medication Group, Treatment Completion, and their interactions on measures of drinking, both during the 12-week treatment period and a 6-month follow-up period. Results : Although there were no main effects of Alcoholic Subtype or Medication Group, subjects who completed the treatment trial showed significantly better drinking-related outcomes. There was also an interaction of Alcoholic Subtype by Medication Group during treatment. Among type B subjects, fluoxetine treatment resulted in poorer drinking-related outcomes than placebo treatment. Among type A subjects, there was no effect of Medication Group. This interactive effect did not persist during the 6-month follow-up period. Conclusions : Alcoholic subtypes identified by cluster analysis seem to be differentially responsive to the effects of fluoxetine treatment on drinking-related outcomes. Serotonergic abnormalities previously identified among a subgroup of alcoholics who are also characterized by impulsivity and severity of alcohol dependence may help to explain the differential medication effect. Based on these findings, it is recommended that, in the absence of a comorbid mood or anxiety disorder, fluoxetine not be used to maintain abstinence or reduce drinking in high-risk/severity alcoholics.     

A Double-Blind, Placebo-Controlled Study of Nortriptyline and Bromocriptine in Male Alcoholics Subtyped by Comorbid Psychiatric Disorders

This double-blind, placebo-controlled, 6-month follow-up treatment study investigated the efficacy of bromocriptine and nortriptyline in attenuating drinking behavior and psychiatric symptoms in 216 male alcoholic patients subtyped by comorbid psychiatric disorder(s). Three well-defined subtypes were examined: alcoholism only, alcoholism + affective/anxiety disorder, and alcoholism + antisocial personality disorder. It was hypothesized that both medications would relieve negative affective symptoms associated with alcohol use and would be particularly effective for the affective/anxiety subgroup. Contrary to our predictions, the only significant effects found were with the antisocial personality disorder patients who were receiving nortriptyline. One interpretation of the results was that nortriptyline may have reduced impulsive drinking in the antisocial personality disorder subgroup by actions on serotonergic neurotransmission.     

Advances in the pharmacotherapy of alcoholism: challenging misconceptions

This article highlights the proceedings of a symposium presented at the 28th Annual Scientific Meeting of the Research Society on Alcoholism in Santa Barbara, CA, June 27, 2005. The organizer and chair was Henry R. Kranzler. The presentations included: (1) Introduction, by Henry R. Kranzler; (2) Neurobiology of Alcohol Dependence: Implications for Medical Treatment, by George Koob; (3) Advances in Alcoholism Pharmacotherapy, by Henry R. Kranzler; (4) Patient Acceptance of Alcoholism Pharmacotherapy, by David R. Gastfriend; (5) System Challenges in the Adoption of Pharmacotherapy, by Robert M. Swift; and (6) Pharmacotherapy for Alcohol Dependence: Strengths, Challenges, and Future Directions, by Mark L. Willenbring.     

Asthma Knowledge and Medication Compliance Among Parents of Asthmatic Children in Nanjing,China

Asthma knowledge and medication compliance among parents of 150 asthmatic children in Nanjing were assessed using a self-administered questionnaire. The results showed that 54.7% of parents had poor knowledge of asthma and its management. Parental compliance with medication was also suboptimal as only 43.3% of parents reported adherence with prescribed anti-asthmatic medication for their children. Reasons for non-compliance included fear of medication side-effects and tolerance, and forgetting to give the child's medication. Education and occupation were found to be associated with asthma knowledge, however there was no association between age or income with knowledge. Income was associated with compliance with asthma medication, however no association was found between parents’ age, education, occupation, or asthma knowledge with compliance. This study has identified the need for accurate and up-to-date information on asthma for parents of asthmatic children as well as programs aimed at teaching parents skills in managing their child's asthma. There is also the need for strategies aimed at improving communication between the health provider and parents of asthmatic children.     

Asthma Knowledge and Medication Compliance Among Parents of Asthmatic Children in Nanjing, China

Asthma knowledge and medication compliance among parents of 150 asthmatic children in Nanjing were assessed using a self-administered questionnaire. The results showed that 54.7% of parents had poor knowledge of asthma and its management. Parental compliance with medication was also suboptimal as only 43.3% of parents reported adherence with prescribed anti-asthmatic medication for their children. Reasons for non-compliance included fear of medication side-effects and tolerance, and forgetting to give the child's medication. Education and occupation were found to be associated with asthma knowledge, however there was no association between age or income with knowledge. Income was associated with compliance with asthma medication, however no association was found between parents' age, education, occupation, or asthma knowledge with compliance. This study has identified the need for accurate and up-to-date information on asthma for parents of asthmatic children as well as programs aimed at teaching parents skills in managing their child's asthma. There is also the need for strategies aimed at improving communication between the health provider and parents of asthmatic children.     

Anger in an Inpatient Treatment Sample of Chronic Alcoholics

Four measures of anger were investigated in sober male and female alcoholics and nonalcoholic peers. The relationships among anger variables, past drinking behavior, and substance abuse consequences in alcoholics were explored. Additionally, the interrelationships among anger, depression, and anxiety in the groups were examined, and the relationships between an overall dysphoria index and drinking behavior and substance abuse consequences were determined. 104 alcoholics (sober 21 to 45 days) and 70 community controls, aged 21 to 56, were given the Spielberger Anger Expression Inventory, the Beck Depression Inventory, and the Spielberger State Anxiety Inventory. Alcoholics scored higher than controls on Trait Anger, Anger-In, and Anger-Out, but not on State Anger. There were no main effects of sex. Anger-In was significantly negatively correlated with the Quantity-Frequency Index in alcoholic males. Anger-In was significantly positively correlated with depression in male and female alcoholics and with substance abuse consequences in the latter group. The depression measure was significantly correlated with consequences in female, but not in male alcoholics. These data have treatment implications, especially for female alcoholics.     

Evaluating readiness and treatment seeking effects in a pharmacotherapy trial for alcohol dependence

BACKGROUND: Decreases in drinking behavior prior to treatment onset often occur in pharmacotherapy trials for alcohol dependence. We propose that these decreases are associated with both trait and state factors operating before initiation of treatment to influence participants' expectation or perception of future treatment outcome. While trait factors typically include personality traits, state factors can include readiness to change and severity of drinking at screening. Understanding the characteristics of changes in drinking early in the process of entering treatment can improve clinical trials and outcomes. Our goal was to evaluate drinking behavior before initiating a randomized, double-blind pharmacotherapy clinical trial for alcohol dependence. METHODS: We examined the impact of personality factors associated with gregariousness or conformity on the MacAndrew Alcoholism Scale, as well as state factors measured by the Stages-of-Change Scale (based on the University of Rhode Island Change Assessment Scale) and quantity of drinking at screening, on pre-double-blind clinical outcome (i.e., drinking reduction) among 321 male and female alcoholics enrolled in a pharmacotherapy trial. RESULTS: A significant reduction in alcohol consumption occurred among heavy drinkers between the baseline assessment (10.3 +/- 5.9 drinks per day) and the last week of single-blind placebo administration (5.3 +/- 5.1 drinks per day; p < 0.001). In contrast, the reduction in alcohol consumption by nonheavy drinkers over the same period was not significant (from 3.07 +/- 0.65 to 2.98 +/- 2.6 drinks per day; p > 0.05). Partial correlations indicated that the significant predictors of drinking reductions during this period were: level of drinking (-0.215) and the Stages-of-Change subscales of precontemplation (-0.152), contemplation (0.144), and maintenance (-0.284). Personality factors on the MacAndrew Alcoholism Scale did not predict drinking reductions during this same period. CONCLUSIONS: Participants with higher motivation levels and greater drinking severity were most likely to reduce their drinking behavior before double-blind treatment. These state factors are important to consider when randomizing participants in trials, and are more important than trait or personality factors in accounting for the initial reduction in drinking in this population during the pretreatment period.     

A 2-Year Follow-Up of 120 Swedish Female Alcoholics Treated Early in Their Drinking Career: Prediction of Drinking Outcome

BACKGROUND: One hundred twenty women alcoholics recruited to a treatment program called EWA (Early Treatment for Women With Alcohol Addiction) were studied. The selected women were not previously treated for alcohol abuse. METHODS: The women were followed up by use of a structured personal interview, biomarkers sensitive for alcohol abuse (i.e., glutamyl transpeptidase), and questionnaires, by using defined criteria for abstinence, social drinking, satisfactory drinking outcome, and unsatisfactory drinking outcome. RESULTS: Drinking outcome was good (i.e., total abstinence, social drinking, or satisfactory drinking outcome) for 67% of the women during the total follow-up time, by use of strict criteria for relapse. The results were corroborated by the biomarkers. Similar results were reported from two previously studied groups of women from the same department. However, the frequency of abstinence was higher and social drinking was significantly lower among this sample of women. Daily drinking, the use of sedatives, and a long duration of pretreatment alcohol abuse predicted an unfavorable outcome. However, a long duration of outpatient treatment predicted a good outcome, whereas treatment dropout was related to an unsatisfactory drinking outcome. A majority of the women (96%) rated the treatment experience and the treatment program favorably. The overall good results might reflect the selection of the subjects studied. CONCLUSIONS: Improving treatment program adherence would probably improve outcome for the women with an unsatisfactory drinking outcome.     

Six- and Twelve-Month Abstinence Rates in Inpatient Alcoholics Treated with Aversion Therapy Compared with Matched Inpatients from a Treatment Registry

Two hundred forty-nine patients who were treated for alcoholism in an inpatient multimodal treatment program that included aversion therapy were matched post hoc on 17 baseline variables with patients from a national treatment outcome registry. The latter patients received inpatient treatment that emphasized individual and group counseling as the primary therapeutic elements but did not include aversion therapy for alcohol. Six- and 12-month abstinence rates from alcohol and all mood-altering chemicals are reported. The patients treated with aversion therapy for alcohol had higher alcohol abstinence rates at 6 and 12 months (p less than 0.01). The abstinence rates from all mood-altering chemicals were higher in the aversion group at 6 months (p less than 0.05) but not at 12 months. The largest differences between treatment groups in 6-month alcohol abstinence rates were noted for males (p less than 0.001), those over 35 (p less than 0.001), daily drinkers (p less than 0.001), and those with alcohol-related work performance problems (p less than 0.05).     

Isradipine and Naltrexone in Combination with Isradipine Interact with a Period of Abstinence to Reduce Rats'Intakes of an Alcoholic Beverage

Individually housed rats were placed on a daily regimen of only 2 hr a day to drink both water and a sweetened alcoholic beverage. Initially, rats took little ethanol, but after 3 weeks, they took, on average, >2.0 g/kg daily. With achievement of stable intakes, the rats were deprived of opportunity to drink ethanol for 24 days and then the daily regimen was reinstated. With the reinstatement, various injections were given daily for 25 days or more: placebos, doses of isradipine (1.0 or 3.0 mg/kg), naltrexone (3.0 mg/kg), and a combination of isradipine (1.0 mg/kg) and naltrexone (3.0 mg/kg). The combination produced favorable effects with the fewest limiting side-effects. The period of abstinence decreased daily intakes of ethanol and interacted with the drugs to produce large, sustained decreases in intakes of ethanol.     

Development and Initial Validation of a Measure of Drinking Urges in Abstinent Alcoholics

Although drinking urges and cravings are commonly reported by alcoholics, prospective studies have found inconsistent associations between such urges and drinking relapses. Previous studies have measured drinking urges by use of single-item ratings of alcohol craving or other measures of unknown reliability and validity. To permit improved evaluation of hypotheses regarding alcohol craving, a 49-item questionnaire that reflects several urge-related domains was developed and pretested. Items assessed subjects'desire for a drink, expectations of positive effects following drinking, relief of withdrawal and negative affect following drinking, and intention to drink. Exploratory and confirmatory factor analyses of the responses of 351 abstinent, treatment-seeking alcoholics indicated that alcohol urges are best described by a single factor. Based on these analyses, an internally consistent, reliable, and psychometrically valid 8-item scale, the Alcohol Urge Questionnaire (AUQ), was developed. Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol, and that they declined with prolonged abstinence. The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations.     

Examination of Cloninger''s Type I and Type II Alcoholism with a Sample of Men Alcoholics in Treatment

Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age-of-onset of problem drinking and symptom-clusters supposedly associated with each subtype. Marked overlap was found between the symptom-clusters used to define the two subtypes. Ninety-one percent of the entire sample satisfied criteria for both symptom-clusters. Dividing the sample by early-onset (Type II, less than or equal to 25 years) and late-onset (Type I, greater than 26 years) alcoholism did not substantially reduce the overlap between symptom-clusters; i.e., 96% of the early-onset and 83% of the late-onset subgroups were positive for both symptom-clusters. Only 21 men (6%) could be classified when both age-of-onset and the type-appropriate symptom-cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two-group clinical alcoholism typology proposed by Cloninger basically reflects the age-of-onset of problem drinking.     

Compliance with a critical pathway for the management of febrile neutropenia and impact on clinical outcomes

Febrile neutropenia is associated with significant morbidity and mortality. Managing infectious in neutropenic patients remains a dynamic process, making necessary timely and efficient empirical antibiotic therapy. The implementation of critical pathways has been suggested as a strategy to improve clinical effectiveness. This study evaluated the compliance with an institutional critical pathway for the management of febrile neutropenia and the impact on clinical outcomes at Hospital de Clínicas de Porto Alegre, Brazil (HCPA). We performed a cohort study that prospectively included patients hospitalized from January 2004 to December 2005 and presented febrile neutropenia (190 episodes). Historical controls were selected from March 2001 to April 2003 (193 episodes) before the critical pathway was introduced. This study showed a low rate of full compliance (21.6%; 95% CI 15.7–27.5) with the critical pathway. In most cases, there was partial compliance (67.9%; 95% CI 61.3–74.5). Despite the moderate adherence observed, we recorded a decrease in in-hospital all-cause mortality in the sample studied after protocol implementation (from 24.4 to 14.4%; P = 0.017) and reduction in the length of use of cephalosporin and quinolones. In conclusion, implementation of a critical pathway seems to be an effective strategy to improve clinical outcomes in patients hospitalized with febrile neutropenia. Financial support: FIPE/HCPA (Fundo de Incentivo à Pesquisa).     

Effectiveness of naltrexone in a community treatment program

OBJECTIVE: In several large, well-designed, randomized, double-blind studies, the opiate antagonist naltrexone demonstrated efficacy in the treatment of alcohol dependence. Specifically, when combined with certain psychosocial therapies, naltrexone reduces the number of drinking days, heavy drinking, and time to relapse to alcohol use in alcohol-dependent individuals. Whether this efficacy can be generalized to individuals who have alcohol use disorders and present for treatment at front-line community treatment programs has not been well established. METHODS: A total of 145 patients who presented for treatment at a rural community substance abuse treatment center were randomized to receive naltrexone 50 mg daily plus usual program treatment (n = 54), placebo plus usual treatment (n = 43), or usual treatment alone (n = 48) for 12 week. A total of 133 participants had at least one follow-up visit. Primary outcome measures included percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days (four or more for women and six or more for men), and time to first heavy drinking day. Secondary measures included changes in serum biological markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase), craving, and psychosocial functioning. RESULTS: In the intention-to-treat analysis, there were no between-group differences for any of the primary drinking outcomes at 12 weeks. In post hoc exploratory analyses, the entire sample of participants was divided into two new groups: (1) people who drank during the 2 weeks before the start of medication (entry drinkers) and (2) people who did not drink during this interval (entry abstainers). Entry abstainers were at an advantage at study entry in that they were significantly more likely to have an inpatient hospitalization immediately before entry into outpatient treatment. Mixed-model analysis of variance revealed a main effect for entry group at the 12-week treatment endpoint on the primary outcome measures of percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days, and time to first heavy drinking day. Participants in any of the randomized groups who were entry abstainers had significantly better improvement on all of the primary outcome measures. The abstainer groups that were randomized to placebo and usual treatment had significantly better outcomes than the entry drinkers in those perspective groups. However, for the naltrexone-treated group, entry drinkers and entry abstainers had similar improvement in drinking-related outcomes. CONCLUSIONS: These data suggest that naltrexone may offer particular benefit to patients who continue to drink during the early stages of the trial as compared with those who have achieved abstinence before treatment entry.     

Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study

BACKGROUND: Clinical studies with opioid antagonists for treatment of problem drinking have mainly been conducted in specialized alcohol treatment centers, included structured psychosocial treatment, and have focused on maintaining abstinence after a period of abstinence from alcohol. METHODS: This multisite, randomized double-blind study investigated targeted nalmefene in reducing heavy drinking. Specialized alcohol treatment centers and private general practices enrolled 403 subjects (328 men, 75 women). Subjects were instructed to take nalmefene 10 to 40 mg (n=242) or placebo (n=161) when they believed drinking to be imminent. After 28 weeks, 57 subjects from the nalmefene group continued into a 24-week randomized withdrawal extension. Concomitant psychosocial intervention was minimal and no treatment goals were imposed. Alcohol consumption was recorded using the time-line follow-back method. Biochemical indicators of alcohol use were also measured. RESULTS: The mean monthly number of heavy drinking days (HDDs) during the 12-week period before inclusion was 15.5 (SD 6.9) in the nalmefene group and 16.2 (SD 6.9) in the placebo group. During treatment, the mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in the placebo group (p=0.0065). The levels of serum alanine aminotransferase and gamma-glutamyl transferase decreased in the nalmefene group compared with the placebo group (p=0.0088 and 0.0023). During the randomized withdrawal period, subjects randomized to placebo apparently returned to heavier drinking. Subjects receiving nalmefene reported more nausea, insomnia, fatigue, dizziness, and malaise than subjects on placebo. CONCLUSIONS: Nalmefene appears to be effective and safe in reducing heavy drinking, even when accompanied by minimal psychosocial support.     

Changes in the Episodic Memory and Executive Functions of Abstinent and Relapsed Alcoholics Over a 6-Month Period

Background: It is still unclear whether episodic memory and executive functions capacities can return to normal in abstinent patients over a 6‐month period. Furthermore, the role of interim drinking in cognitive recovery is still not well known. Finally, further research is required to specify the predictive value of cognitive abilities at initial testing in the treatment outcome (abstinence or relapse) . The aims of the present study were therefore to measure changes in episodic memory and executive functions over a 6‐month period in abstinent and relapsed alcoholics and to ascertain whether neuropsychological results at treatment entry can predict treatment outcome at follow‐up. Methods: Fifty‐four alcoholic patients and 54 matched control subjects performed baseline neuropsychological tasks assessing episodic memory, executive functions, the slave systems of working memory and attentional abilities. At the follow‐up session (i.e., 6 months later), episodic memory and 3 executive functions (inhibition, flexibility, and updating) were re‐examined in the alcoholic patients. Results: Results showed that over the 6‐month interval, the abstainers’ episodic memory and executive performances had returned to normal, whereas the relapsers performed lower than before in the flexibility task. Episodic memory and executive functions recovery was correlated, in abstainers, with drinking history and age respectively. Finally, there was no significant difference regarding neuropsychological scores at baseline between abstainers and relapsers. Discussion: Over the 6‐month interval, abstainers normalized episodic memory and executive performances whereas relapsers obtained executive results which were more severely impaired, emphasizing the influence of interim drinking on cognitive changes. Episodic memory, executive functions, the slave systems of working memory and attentional abilities did not appear to be reliable predictors of treatment outcome over a 6‐month interval.     

Effects of ondansetron in early- versus late-onset alcoholics: a prospective,open-label study

BACKGROUND: Early-onset alcoholics (EOAs) have a greater familial loading for alcoholism, more severe progression of the disorder, a greater severity of comorbid psychopathology, and a poorer response to treatment than late-onset alcoholics (LOAs). Ondansetron, a 5-hydroxytryptamine-3 antagonist, was found to be superior to placebo in the treatment of EOAs, but not of LOAs. This study compared the tolerability and potential efficacy of an oral solution of ondansetron in EOAs versus LOAs. METHODS: Forty outpatients with alcohol dependence (67.5% male; 87.5% European American; 20 EOAs; 20 LOAs) received an oral solution of ondansetron at a dosage of 4 microg/kg twice daily for 8 weeks, together with weekly relapse-prevention therapy. RESULTS: EOAs had a significantly greater decrease in drinks per day, drinks per drinking day, and alcohol-related problems than LOAs. Changes in the level of carbohydrate-deficient transferrin were consistent with changes in self-reported drinking behavior. CONCLUSIONS: An oral solution of ondansetron seems suitable for the treatment of alcohol dependence, yielding findings consistent with evidence from a placebo-controlled trial that ondansetron, at a dosage of 4 microg/kg twice daily, is of value in the treatment of EOAs.