Randomized trial of web-based training to promote counselor use of cognitive behavioral therapy skills in client sessions.

BACKGROUND AND METHODS: The authors designed and delivered an innovative Web course on cognitive behavioral therapy (CBT), a specific empirically based treatment, to a diverse group of addiction counselors and supervisors in 54 addiction units across the country, and conducted a randomized controlled trial of its effectiveness with 127 counselors. The primary focus of the trial was to assess "adequate adherence to CBT practice" after training as judged by raters blinded to training condition who listened to audiotapes of actual client sessions. Counselors who passed were judged to satisfy 2 criteria: (a) low pass or greater on at least 1 of 3 "CBT-generic skills" assessing session structure; and (b) low pass or greater on at least 1 of 3 "CBT-specific skills" related to use of functional analysis, cognitive skills practice, or behavioral skills practice. RESULTS: Although the counselors' use of CBT skills in sessions increased after Web course training, it was not statistically significant and not larger than the gain of control-group counselors trained with a written CBT manual.

Alcohol treatment effects on secondary nondrinking outcomes and quality of life: the COMBINE study.

OBJECTIVE: To evaluate the full range of alcohol treatment effectiveness, it is important to assess secondary nondrinking outcome dimensions in addition to primary alcohol consumption outcomes. METHOD: We used a large sample (n=1,226) of alcohol-dependent participants entering the National Institute on Alcohol Abuse and Alcoholism-sponsored COMBINE (Combining Medications and Behavioral Interventions) Study, a multisite clinical trial of pharmacological (naltrexone [ReVia] and acamprosate [Campral]) and behavioral interventions, to examine the effects of specific treatment combinations on nondrinking functional outcomes. We assessed the outcomes at baseline and at the end of 16 weeks of alcohol treatment and again at the 26-week and/or 52-week postrandomization follow-ups. RESULTS: (1) Drinking and secondary outcomes were significantly related, especially at the follow-up periods. A higher percentage of heavy drinking days, more drinks per drinking day, and lower percentage of days abstinent were associated with lower quality-of-life measures. (2) All nondrinking outcomes showed improvement at the end of 16 weeks of treatment and most maintained improvement over the 26-week and 52-week follow-ups. Only two measures returned to pretreatment levels at 52 weeks: percentage of days paid for work and physical health. Improvements of nondrinking outcomes remained even after adjusting for posttreatment heavy drinking status. (3) Although nondrinking outcomes showed overall improvement, specific pharmacological and behavioral treatment combinations were not differentially effective on specific secondary outcomes. CONCLUSIONS: In the current study, changes that resulted from treatment were multidimensional, and improvements in nondrinking outcomes reflected the overall significant improvement in drinking but they were not differentiated between treatment combination groups. Findings from this study support the importance of including secondary nondrinking outcomes in clinical alcohol-treatment trials.

Do patients with alcohol dependence respond to placebo? Results from the COMBINE Study.

OBJECTIVE: The purpose of this study was to examine the nature of the effect of placebo medication plus accompanying medical management in the treatment of alcohol dependence. METHOD: The National Institute on Alcohol Abuse and Alcoholism COMBINE (Combining Medications and Behavioral Interventions) study, a randomized controlled double-blind trial of 1,383 alcohol-dependent patients, compared combinations of medications (acamprosate [Campral] and naltrexone [ReVia]) and behavioral therapy (medical management and specialist-delivered behavioral therapy) for alcohol dependence. This report focuses on a subset of that study population (n = 466) receiving (1) specialized behavioral therapy alone (without pills), (2) specialized behavioral therapy + placebo medication + medical management, or (3) placebo + medical management. RESULTS: During 16 weeks of treatment, participants receiving behavioral therapy alone had a lower percentage of days abstinent (66.6%) than did the participants receiving placebo and medical management (73.1%) or those receiving specialized behavioral therapy + placebo + medical management (79.4%). The group receiving behavioral therapy alone relapsed to heavy drinking more often (79.0%) than those receiving behavioral therapy + placebo + medical management (71.2%). This report focuses on potential explanations for this finding. The two groups of participants receiving placebo + medical management were more likely to attend Alcoholics Anonymous meetings during treatment (32.7% and 32.0% vs 20.4%) and were less likely to withdraw from treatment (14.1% and 22.9% vs 29.3%). CONCLUSIONS: There appeared to be a significant "placebo effect" in the COMBINE Study, consisting of pill taking and seeing a health care professional. Contributing factors to the placebo response may have included pill taking itself, the benefits of meeting with a medical professional, repeated advice to attend Alcoholics Anonymous, and optimism about a medication effect.

Characteristics of first-time alcohol treatment seekers: the COMBINE Study.

OBJECTIVE: The current study compared alcoholics who entered treatment for the first time with those who had reported one or more prior treatment experiences using a large sample (N = 1,362) of alcoholics who entered the National Institute on Alcohol Abuse and Alcoholism-sponsored COMBINE (Combining Medications and Behavioral Interventions) Study of pharmacological and behavioral treatment efficacy. METHOD: Participants were categorized into three prior-treatment groups: (1) treatment naive (n = 691, 50.73%), (2) one to two prior treatments (n = 380, 27.90%), or (3) three or more prior treatments (n = 291, 21.37%). Groups were compared at baseline on multiple drinking and psychosocial variables. RESULTS: The treatment-naive group was more likely to be female, educated, married, and employed. They reported the lowest levels of drinks per drinking day, average drinks per day, alcohol dependence, craving, and alcohol-related consequences; but, they had the oldest age at onset of alcohol problems. Both the treatment-naive group and the one-to-two prior-treatment group had lower percentage days abstinent within the prior 30 days, compared with the three-or-more group (22% and 25% vs 32%, respectively). The treatment-naive group reported the least commitment to an abstinence goal (43% vs 70% and 80%, respectively) and the lowest mean number of Alcoholics Anonymous meetings attended (0.86 vs 3.10 vs 6.91, respectively). They also reported fewer psychological symptoms, less distress, and higher levels of quality of life on physical, emotional, and environmental domains, as well as social relationships. CONCLUSIONS: Results suggest that a greater understanding of treatment-naive versus treatment-experienced clients may provide a better profile of help-seeking behavior and may suggest different approaches to treatment.

Quetiapine versus trazodone in reducing rehospitalization for alcohol dependence: a large data-base study.

Clinicians commonly use nonindicated (or "off-label") medications for the treatment of alcoholism, although there is no clear evidence to support this practice. Quetiapine and trazodone are 2 medications frequently used in this manner, especially to treat sleep disturbance associated with alcohol withdrawal. Using national administrative data from the Department of Veterans Affairs, we compared the differences among these medications in time to rehospitalization after discharge from an index hospitalization for alcohol dependence. Our outcome measure was the difference in time (weeks) to rehospitalization for patients given medications in 1 of 4 groups: quetiapine alone (median, 6.1 weeks); trazodone alone (median, 10.1 weeks); quetiapine combined (median, 7.1 weeks); and trazodone combined (median, 10.3 weeks) with other frequently used psychotropic drugs. Differences between groups were examined with Cox's proportional hazards regression using trazodone in combination with other medications as the reference category. Crude hazard ratios were determined first and then adjusted for covariates. There was no difference in the risk of rehospitalization when patients using quetiapine in combination were compared with the reference category (hazard ratio [HR] = 1.08; confidence interval [CI], 0.99-1.17; P < 0.0936). In contrast, when quetiapine was used alone there was a significantly higher risk of rehospitalization (HR = 1.22; CI = 1.06-1.41; P < 0.005). When trazodone was used alone there was no difference in risk in the unadjusted analysis (HR = 1.05; CI = 0.96-1.14; P < 0.3076); however, the HR increased to a significant level after adjusting for covariates (HR, 1.14; CI = 1.05-1.24; P < 0.0029) and for those with 2+ previous discharges (HR = 1.25; CI = 1.14-1.37; P < 0.0001). These findings suggest the need for additional studies to better understand what symptoms of alcoholism benefit from the use of these medications, at what dose levels, and with what other medication combinations.

Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.

CONTEXT: Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. OBJECTIVES: To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS: Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. MAIN OUTCOME MEASURES: Percent days abstinent from alcohol and time to first heavy drinking day. RESULTS: All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. CONCLUSIONS: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006206.

When worlds collide: blending the divergent traditions of pharmacotherapy and-psychotherapy outcome research.

OBJECTIVE: The multisite COMBINE Study brought together a team of alcoholism investigators who varied in whether their expertise was primarily in pharmacotherapy research or in studying psychotherapy. The process of designing a single trial that tested combinations of psychotherapy and pharmacotherapy highlighted the differences in these two research traditions and necessitated a number of compromises that are the focus of this article. METHOD: The COMBINE trial was designed to investigate the efficacy, separately and in combination, of two medications (i.e., naltrexone, acamprosate) with Medical Management and a state-of-the-art psychotherapy, known as the Combined Behavioral Intervention. RESULTS: Pharmacotherapy researchers favored studying outcome during the treatment period when medications were administered, viewing behavioral intervention as a means for minimizing variance during treatment and providing ethical care in placebo-controlled studies. In contrast, psychotherapy researchers focused on assessment of outcomes after treatment, regarding the behavioral intervention as a source of long-lasting change, necessitating careful training and monitoring of its implementation. The two traditions also differed on variables of interest in studying treatment process and secondary outcomes and methods of data collection and analysis. Some of the solutions reached by the COMBINE Study Research Group included studying both the short-term and long-term effects of treatment and selective inclusion of measures designed to evaluate processes specific to medications and to behavioral interventions. CONCLUSIONS: The successful compromises reached by the COMBINE Study Research Group may be helpful to other transdisciplinary research teams undertaking a combined evaluation of promising medications and behavioral interventions for alcoholism.

Use of a "psychotherapy with no pills" treatment condition as part of a combined pharmacotherapy-psychotherapy research study of alcohol dependence.

OBJECTIVE: The purpose of this article is to review issues related to the use of placebo medication in a study examining combined pharmacotherapy and psychotherapy for alcohol dependence. METHOD: Little is known about the strength of the placebo effect in alcohol-dependent patients. One way to study this is to compare placebo to no pharmacological treatment. The multisite National Institute on Alcohol Abuse and Alcoholism COMBINE Study is examining optimal combinations of two medications (acamprosate and naltrexone) and two behavioral treatments (a moderate-intensity treatment called Combined Behavioral Intervention [CBI] and a low-intensity treatment called Medical Management [MM]) for alcohol-dependent patients. The study initially included a 2 x 2 x 2 eight-cell design. This article relates our experience adding a ninth treatment condition (Cell 9), consisting of CBI alone, with no pills or MM. By comparing patients receiving CBI alone to patients receiving two placebos, MM and CBI, we can examine the strength of the placebo effect for these two medications in alcohol-dependent patients. Moreover, we can study CBI in the context in which it is frequently delivered clinically, that is, in the absence of pharmacotherapy and certainly in the absence of placebo medication. RESULTS: This article explains the background and rationale behind the decision to include Cell 9 in COMBINE. Recruitment challenges faced as a result of adding this condition are reviewed, as is the experience implementing this condition in a pilot feasibility study. CONCLUSIONS: The use of a "psychotherapy with no pills" treatment condition as part of a combined pharmacotherapy-psychotherapy study of alcohol dependence is feasible and can help enrich the results of this research.

Origins, issues and options in the development of the combined behavioral intervention.

OBJECTIVE: The aim of the investigators was to develop a moderate intensity comprehensive behavioral treatment based on the principles of motivational interviewing and Cognitive Behavioral Therapy that, within the confines of a standardized abstinence-oriented treatment, would provide a broad spectrum of modules to assist those seeking treatment to achieve reduction of problematic drinking. METHOD: The core issue of how to deliver a flexible therapy tailored to the needs of individual clients while at the same time providing a standardized treatment protocol for a randomized clinical trial provided the dilemma out of which this unique standardized protocol arose. By using a single decision tree, client choice, combined with limited options, we were able to reconcile these conflicting demands. RESULTS: Key decisions that were made in developing the treatment protocol and the thinking leading to these decisions are described. CONCLUSIONS: Understanding these key issues and the factors that led to the decisions made will assist would-be users in their own clinical and/or clinical research needs.

A relaxation response randomized trial on patients with chronic heart failure.

PURPOSE: Patients with various medical conditions benefit from eliciting the relaxation response (RR), using a variety of techniques, but few studies have focused on chronic heart failure (CHF). We evaluated the efficacy of an RR intervention program on the quality of life (QOL) and exercise capacity of CHF patients by conducting a single-blind, 3-arm, randomized, controlled trial. METHODS: Between April 2000 and June 2002, we enrolled 95 patients with moderate severity CHF from the Veterans Affairs Boston Healthcare System. Patients in the study intervention group attended a weekly RR group for 15 weeks and were requested to practice the techniques at home twice a day. A 15-week cardiac education (EDU) program was used as an alternative intervention, and usual care (UC) was the control group. The QOL questionnaires and a bicycle test were administered at baseline and after intervention or 15 to 19 weeks. RESULTS: Eighty-three (87%) of the 95 enrolled patients completed both baseline and post-intervention QOL measures (31 RR, 24 EDU, and 28 UC). No dropout bias was observed. The RR group had significantly better QOL change scores in peace-spiritual scales than did the UC group (P = .02), adjusting for baseline scores, time between assessments, age, education, diet, and medication, whereas no significant difference was observed between the EDU and UC groups. A similar trend was observed in emotional QOL (RR and UC group comparison, P = .07). No statistically significant intervention effect on physical QOL or exercise capacity was observed. CONCLUSIONS: A short RR intervention can improve some aspects of QOL in CHF patients.

Relaxation response for Veterans Affairs patients with congestive heart failure: results from a qualitative study within a clinical trial.

Fifty-seven veterans with congestive heart failure were interviewed about their experiences and changes after participating in a three-armed randomized trial: relaxation response (RR) training, cardiac education, and usual care. The interviews were tape-recorded, transcribed, and analyzed. Half of the 20 RR group interviewees reported physical improvements, and 13 reported emotional improvements. These improvements went beyond disease management to lifestyle changes and improved family/friends relationships. Five of 16 cardiac education group interviewees reported physical improvements, and eight reported emotional improvements. These improvements consisted of a better understanding of the disease and resulted in feeling more at ease. None of the usual care group interviewees reported any improvement from study participation. Although group support contributed to the benefits reported by RR and cardiac education groups, the use of the RR techniques seems to be the factor that distinguished the improvements. The value of the RR in congestive heart failure health care is suggested by the results.

Patient recruitment to a randomized clinical trial of behavioral therapy for chronic heart failure.

BACKGROUND: Patient recruitment is one of the most difficult aspects of clinical trials, especially for research involving elderly subjects. In this paper, we describe our experience with patient recruitment for the behavioral intervention randomized trial, "The relaxation response intervention for chronic heart failure (RRCHF)." Particularly, we identify factors that, according to patient reports, motivated study participation. METHODS: The RRCHF was a three-armed, randomized controlled trial designed to evaluate the efficacy and cost of a 15-week relaxation response intervention on veterans with chronic heart failure. Patients from the Veterans Affairs (VA) Boston Healthcare System in the United States were recruited in the clinic and by telephone. Patients' reasons for rejecting the study participation were recorded during the screening. A qualitative sub-study in the trial consisted of telephone interviews of participating patients about their experiences in the study. The qualitative study included the first 57 patients who completed the intervention and/or the first follow-up outcome measures. Factors that distinguished patients who consented from those who refused study participation were identified using a t-test or a chi-square test. The reason for study participation was abstracted from the qualitative interview. RESULTS: We successfully consented 134 patients, slightly more than our target number, in 27 months. Ninety-five of the consented patients enrolled in the study. The enrollment rate among the patients approached was 18% through clinic and 6% through telephone recruitment. The most commonly cited reason for declining study participation given by patients recruited in the clinic was 'Lives Too Far Away'; for patients recruited by telephone it was 'Not Interested in the Study'. One factor that significantly distinguished patients who consented from patients who declined was the distance between their residence and the study site (t-test: p <.001). The most frequently reported reason for study participation was some benefit to the patient him/herself. Other reasons included helping others, being grateful to the VA, positive comments by trusted professionals, certain characteristics of the recruiter, and monetary compensation. CONCLUSIONS: The enrollment rate was low primarily because of travel considerations, but we were able to identify and highlight valuable information for planning recruitment for future similar studies.