Janet C. Blodgett

Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: When are these medications most helpful?

AIMS Although debates over the efficacy of oral naltrexone and acamprosate in treating alcohol use disorders tend to focus on their global efficacy relative to placebo or their efficacy relative to each other, the underlying reality may be more nuanced. This meta-analysis examined when naltrexone and acamprosate are most helpful by testing: (i) the relative efficacy of each medication given its presumed mechanism of action (reducing heavy drinking versus fostering abstinence) and (ii) whether different ways of implementing each medication (required abstinence before treatment, detoxification before treatment, goal of treatment, length of treatment, dosage) moderate its effects. METHODS A systematic literature search identified 64 randomized, placebo-controlled, English-language clinical trials completed between 1970 and 2009 focused on acamprosate or naltrexone. RESULTS Acamprosate had a significantly larger effect size than naltrexone on the maintenance of abstinence, and naltrexone had a larger effect size than acamprosate on the reduction of heavy drinking and craving. For naltrexone, requiring abstinence before the trial was associated with larger effect sizes for abstinence maintenance and reduced heavy drinking compared with placebo. For acamprosate, detoxification before medication administration was associated with better abstinence outcomes compared with placebo. CONCLUSIONS In treatment for alcohol use disorders, acamprosate has been found to be slightly more efficacious in promoting abstinence and naltrexone slightly more efficacious in reducing heavy drinking and craving. Detoxification before treatment or a longer period of required abstinence before treatment is associated with larger medication effects for acamprosate and naltrexone respectively.

A meta-analysis of topiramate's effects for individuals with alcohol use disorders.

BACKGROUND Influenced by several trials and reviews highlighting positive outcomes, topiramate is increasingly prescribed as a treatment for alcohol use disorders (AUDs). The only previously published meta-analysis of topiramate for AUDs was limited by a sample of only 3 randomized, placebo-controlled trials (RCTs). METHODS A systematic search identified 7 RCTs (including a total of 1,125 participants) that compared topiramate to placebo for the treatment for AUDs. This meta-analysis estimated the overall effects of topiramate on abstinence, heavy drinking, craving, and γ-glutamyltranspeptidase (GGT) outcomes and included several sensitivity analyses to account for the small sample of studies. RESULTS Overall, the small to moderate effects favored topiramate, although the effect on craving was not quite significantly different from 0. The largest effect was found on abstinence (g = 0.468, p < 0.01), followed by heavy drinking (g = 0.406, p < 0.01), GGT (g = 0.324, p = 0.02), and craving (g = 0.312, p = 0.07) outcomes. Sensitivity analyses did not change the magnitude or direction of the results, and tests did not indicate significant publication bias. The small sample size did not allow for examination of specific moderators of the effects of topiramate. CONCLUSIONS Topiramate can be a useful tool in the treatment of AUDs. Its efficacy, based on the current sample of studies, seems to be of somewhat greater magnitude than that of the most commonly prescribed medications for AUDs (naltrexone and acamprosate). Further research will help to identify the contexts in which topiramate is most beneficial (e.g., dose, concurrent psychotherapy, patient characteristics).

How effective is continuing care for substance use disorders? A meta-analytic review

Given the often chronic nature of substance use disorders, patients sometimes receive less intensive continuing care following an initial period of more intensive treatment. This meta-analysis estimated the effect of continuing care and formally tested several proposed moderators (intervention duration, intensity, modality, and setting) of that effect. A systematic search identified 33 controlled trials of continuing care; 19 included a no/minimal treatment condition and were analyzed to assess the overall effect of continuing care versus control. Continuing care had a small, but significant, positive effect size, both at the end of the continuing care interventions (g=0.187, p<0.001) and at follow-up (g=0.271, p<0.01). Limited by a small number of studies, analyses did not identify any significant moderators of overall effects. These results show that continuing care can provide at least modest benefit after initial treatment. We discuss study characteristics that may have reduced the magnitude of the overall continuing care effect estimate.

Extent and Reporting of Patient Nonenrollment in Influential Randomized Clinical Trials, 2002 to 2010

Because they assign patients to treatment conditions, randomized clinical trials (RCTs) offer unparalleled internal validity for drawing inferences about the efficacy of a medical treatment. Whether such inferences can be generalized is not always clear because many RCTs enroll a low and unrepresentative proportion of all patients.1–6 The challenges of judging the clinical utility of clinical trial results are increased by poor reporting: Gross and colleagues’ study of trials published in leading medical journals from 1999–2000 found that only 28% reported the proportion of screened patients who were enrolled.7 These deficiencies may have been ameliorated in the past decade because the CONSORT statement was revised in 2001 to require more complete information on the enrollment process in reports of clinical trials8, and because many treatment research fields have been showing greater concern about generating knowledge that better informs clinical practice. Accordingly, the present study assessed the extent to which low enrollment rates are still characteristic of widely-cited clinical trials, and whether reporting of enrollment information has improved.

Risk of Recidivism Among Justice-Involved Veterans A Systematic Review of the Literature

Empirical research on recidivism risk among justice-involved veterans (JIVs) is limited. Using the risk-need-responsivity model, we conducted a systematic review of research on risk factors for recidivism among JIVs to identify the gaps in this literature and provide recommendations for future research. Substance abuse and indicators of antisociality were consistently linked to justice involvement in veterans; however, the evidence for negative family/marital circumstances and lack of positive school/work involvement was mixed. Several known risk factors for reoffending among civilian offenders (i.e., antisocial cognitions and associates; lack of prosocial activities) were marked by little to no empirical studies among veterans. Posttraumatic stress and traumatic brain injury, particularly when combined with anger and irritability issues, may be veteran-specific risk factors for violent offending. The implications of these findings for policy and practice and challenges to implementing risk assessments with JIVs are discussed.

Intention-to-treat analyses and missing data approaches in pharmacotherapy trials for alcohol use disorders

Objectives Intention to treat (ITT) is an analytic strategy for reducing potential bias in treatment effects arising from missing data in randomised controlled trials (RCTs). Currently, no universally accepted definition of ITT exists, although many researchers consider it to require either no attrition or a strategy to handle missing data. Using the reports of a large pool of RCTs, we examined discrepancies between the types of analyses that alcohol pharmacotherapy researchers stated they used versus those they actually used. We also examined the linkage between analytic strategy (ie, ITT or not) and how missing data on outcomes were handled (if at all), and whether data analytic and missing data strategies have changed over time. Design Descriptive statistics were generated for reported and actual data analytic strategy and for missing data strategy. In addition, generalised linear models determined changes over time in the use of ITT analyses and missing data strategies. Participants 165 RCTs of pharmacotherapy for alcohol use disorders. Results Of the 165 studies, 74 reported using an ITT strategy. However, less than 40% of the studies actually conducted ITT according to the rigorous definition above. Whereas no change in the use of ITT analyses over time was found, censored (last follow-up completed) and imputed missing data strategies have increased over time, while analyses of data only for the sample actually followed have decreased. Conclusions Discrepancies in reporting versus actually conducting ITT analyses were found in this body of RCTs. Lack of clarity regarding the missing data strategy used was common. Consensus on a definition of ITT is important for an adequate understanding of research findings. Clearer reporting standards for analyses and the handling of missing data in pharmacotherapy trials and other intervention studies are needed.

Prevalence of Mental Health Disorders Among Justice-Involved Veterans

Justice-involved veterans are a special population with unique mental health needs compared with other veterans or justice-involved adults. Prevalence estimates of mental health concerns of justice-involved veterans across 18 samples of these veterans (1987-2013), including both incarcerated and community samples, were identified through a systematic literature search of published studies supplemented by Department of Veterans Affairs Veterans Justice Programs data. Despite heterogeneity across samples and measures used, the review highlights several prominent mental health concerns among veterans. Many justice-involved veterans have likely experienced at least one traumatic event, and many have post-traumatic stress disorder (prevalence from 4% to 39% across samples). At least half of justice-involved veterans have an alcohol and/or drug use disorder (estimates as high as 71% and 65%, respectively), and other psychiatric disorders, such as depression (14%-51%) and psychotic disorders (4%-14%), are common. Justice-involved veterans with comorbid substance use and psychiatric disorders are at increased risk of negative outcomes, including homelessness and violent behavior. Overall, comparisons of justice-involved veterans with other justice-involved adults found a slightly higher rate of mental health concerns among justice-involved veterans, with some indication that intravenous drug use is more prevalent. Compared with other veterans, justice-involved veterans have consistently higher rates of mental health concerns, particularly substance use disorders.

U.S. Department of Veterans Affairs Veterans Justice Outreach Program Connecting Justice-Involved Veterans With Mental Health and Substance Use Disorder Treatment

The Veterans Justice Outreach (VJO) program of the U.S. Veterans Health Administration has a primary mission of linking military veterans in jails, courts, or in contact with law enforcement to mental health and substance use disorder treatment. National data of veterans with VJO contact were used to describe demographic characteristics, and mental health and substance use disorder diagnoses and treatment use and test correlates of treatment entry and engagement using multi-level logistic regression models. Of the 37,542 VJO veterans, treatment entry was associated with being homeless and having a mental health disorder or both a mental health and a substance use disorder versus a substance use disorder only. Being American Indian/Alaskan Native was associated with lower odds of treatment entry. Engagement was associated with female gender, older age, Asian race, urban residence, and homeless status. Increased utilization of substance use disorder treatment, especially pharmacotherapy, is an important quality improvement target.

Sex differences in mental health and substance use disorders and treatment entry among justice-involved Veterans in the Veterans Health Administration

Background:Over half of veterans in the criminal justice system have mental health or substance use disorders. However, there is a critical lack of information about female veterans in the criminal justice system and how diagnosis prevalence and treatment entry differ by sex. Objectives:To document prevalence of mental health and substance use disorder diagnoses and treatment entry rates among female veterans compared with male veterans in the justice system. Research Design:Retrospective cohort study using national Veterans Health Administration clinical/administrative data from veterans seen by Veterans Justice Outreach Specialists in fiscal years 2010–2012. Subjects:A total of 1535 females and 30,478 male veterans were included. Measures:Demographic characteristics (eg, sex, age, residence, homeless status), mental health disorders (eg, depression, post-traumatic stress disorder), substance use disorders (eg, alcohol and opioid use disorders), and treatment entry (eg, outpatient, residential, pharmacotherapy). Results:Among female veterans, prevalence of mental health and substance use disorders was 88% and 58%, respectively, compared with 76% and 72% among male veterans. Women had higher odds of being diagnosed with a mental health disorder [adjusted odds ratio (AOR)=1.98; 95% confidence interval (CI), 1.68–2.34] and lower odds of being diagnosed with a substance use disorder (AOR=0.50; 95% CI, 0.45–0.56) compared with men. Women had lower odds of entering mental health residential treatment (AOR=0.69; 95% CI, 0.57–0.83). Conclusions:Female veterans involved in the justice system have a high burden of mental health disorders (88%) and more than half have substance use disorders (58%). Entry to mental health residential treatment for women is an important quality improvement target.

The Declining Efficacy of Naltrexone Pharmacotherapy for Alcohol Use Disorders Over Time: A Multivariate Meta-Analysis

BACKGROUND Oral naltrexone is an FDA-approved medication for treating alcohol use disorders. Although its efficacy has been supported in multiple clinical trials, an earlier review found that its effect sizes (ESs) on relapse to heavy drinking and, to a lesser extent, percent days drinking were smaller in more recent trials and in multicenter than in single-site studies. We examined whether these findings held when studies from 2004 to 2009 were taken into account, and whether single-site versus multicenter trials, the use of placebo run-in periods, and placebo group improvement accounted for variation in naltrexone effects and decreasing effects over time. METHODS A multivariate meta-analysis of naltrexone pharmacotherapy trials for alcohol use disorders was conducted. All analyses simultaneously modeled ESs on outcomes of percent days abstinent and relapse to heavy drinking. Potential moderators of medication effects that were examined included publication year, multicenter design (vs. single site), placebo run-in period, and placebo group improvement. RESULTS Statistically significant between-group differences on percent days abstinent (the inverse of percent days drinking) and relapse to heavy drinking favored naltrexone over placebo. Year of publication was a significant moderator for both outcomes, with more recent trials having smaller ESs. Neither multi- versus single-site study, the interaction between multi- versus single-site study and year of publication, nor placebo run-in period was a significant moderator of naltrexone effects. Although placebo group improvement was modestly associated with smaller between-group naltrexone versus placebo ESs, only 21 studies provided usable information on placebo group improvement. Within those studies, there was no relationship between naltrexone ESs and time, so placebo group improvement was not examined as a moderator of that relationship. CONCLUSIONS Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.