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Biomedical subjects

David R Gastfriend

Publications and source records attributed to David R Gastfriend.

At least 19 recordsLinked to original sources
PubMed2006

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.

Acamprosate↗
PubMed2006

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.

Alcohol Deterrents↗
PubMed2005

Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial.

CONTEXT: Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited. OBJECTIVE: To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients. DESIGN, SETTING, AND PARTICIPANTS: A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection. INTERVENTION: An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention. MAIN OUTCOME MEASURE: The event rate of heavy drinking days in the intent-to-treat population. RESULTS: Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups. CONCLUSIONS: Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence.

Adult↗
PubMed2005

The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients.

OBJECTIVE: Although cocaine-dependent patients are frequently referred to 12-step self-help groups, little research has examined the benefits of 12-step group attendance in this population. Moreover, the distinction between attending meetings and actively participating in 12-step activities has not typically been examined. METHOD: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, 487 cocaine-dependent outpatients were recruited at five sites for a randomized controlled trial of 24-week behavioral treatments. Study data were examined to see whether self-help attendance or active participation were related to subsequent drug use. RESULTS: Twelve-step group attendance did not predict subsequent drug use. However, active 12-step participation in a given month predicted less cocaine use in the next month. Moreover, patients who increased their 12-step participation during the first 3 months of treatment had significantly less cocaine use and lower ASI Drug Use Composite scores in the subsequent 3 months. Finally, Individual Drug Counseling, based on a 12-step model, and increasing levels of 12-step participation each offered discrete benefits. CONCLUSIONS: Results suggest that active 12-step participation by cocaine-dependent patients is more important than meeting attendance, and that a combination of Individual Drug Counseling and active 12-step participation is effective for these patients.

Adult↗
PubMed2005

Factorial designs in clinical trials: options for combination treatment studies.

OBJECTIVE: This study reviews the use of factorial designs in clinical trials investigating combinations of therapies. METHOD: Factorial designs may be used when (1) the factors are regarded as being independent or (2) the factors are thought to be complementary and a specific aim is to investigate these interactions. We describe what is meant by a factorial design and the issues that need to be addressed when using such a design. We discuss these issues in general and describe how they have been addressed in various prevention trials and in the COMBINE Study, which is a treatment trial of combinations of therapies for alcohol dependence. RESULTS: Trials of type (1) can provide substantial cost savings in conducting multiple unrelated prevention studies in the same group of participants. Such a factorial trial poses few design challenges beyond those of a standard parallel group trial. Trials of type (2) require consideration of aspects that are intrinsic to the factorial design. CONCLUSIONS: A factorial design is a useful way to examine the effects of combinations of therapies, but it poses challenges that need to be addressed in determining the appropriate sample size and in conducting interim and final statistical analyses.

Alcoholism↗
PubMed2005

Design and analysis of trials of combination therapies.

OBJECTIVE: Combination therapies can have significant advantages over monotherapies. Combinations of therapies can provide additive (or even synergistic) effects on efficacy. They may permit use of lower doses of each component to achieve a given level of efficacy, improving tolerability and reducing adverse effects. A multicomponent treatment may facilitate tailoring of therapy to the needs of individual patients (e.g., treatment augmentation in nonresponders). These characteristics seem highly attractive in developing treatment strategies for alcohol abuse and dependence, because existing monotherapies have shown modest efficacy, at best. METHOD: However, trials of combination therapies present challenges in design, execution and interpretation, including: (1) choice of the treatment combinations to be compared; (2) definition of primary and secondary hypotheses; (3) differences between interventions in the duration of treatment, the time lag from the start of treatment to an observable effect on outcomes and interval for assessment of efficacy; (4) study power/sample size; (5) logistics of treatment delivery, masking and outcome assessment; and (6) attribution of adverse events. RESULTS: Most of these issues arose in the COMBINE project, a sequence of trials intended to explore the use of combinations of behavioral and pharmacological approaches in the treatment of alcohol dependence. The resolution and impact of the challenges above for the COMBINE trial will be described. CONCLUSIONS: Trials of combination therapies address many important clinical questions; however, their level of complexity requires considerable forethought, pilot investigations and organization.

Alcoholism↗
PubMed2005

Developing a baseline assessment battery: balancing patient time burden with essential clinical and research monitoring.

OBJECTIVE: Baseline assessment in a multisite alcohol-dependence treatment study has several purposes: addressing inclusion/exclusion criteria and characterizing participants to illuminate subsequent efficacy and safety patterns of the interventions. Combination pharmacotherapy and behavioral therapy trials, however, require more complex assessments than single-modality studies. Medication trials require measures of initial safety for study drug as well as for subsequent side-effect and adverse-effect monitoring (e.g., physical examination, laboratory markers, somatic symptoms, medical conditions and concomitant medications). Behavioral therapy trials (and in some cases medication trials) warrant baseline measurement of mediators of therapy effect (e.g., prior treatment history, motivation for change, self-efficacy, other psychiatric conditions, treatment expectations and network supports). Measures may be needed to interpret interactions that may be discovered between these modalities. METHOD: The National Institute on Alcohol Abuse and Alcoholism COMBINE Study evaluated the potentially overwhelming number of candidate instruments through an iterative process, using the following sequence to finalize a rational baseline assessment battery: key constructs, representative measures, determination of duration of assessment, risk of assessment reactivity, goal priorities, necessity for measure "pruning" and order of measure presentation. After selecting the draft battery, feasibility was evaluated in a pilot study prior to the main trial. RESULTS: The battery was feasible to administer and avoided unintended selection bias. Dropout was substantial, however, and differences across sites in baseline assessment completion rates reflected a tendency of a central intake model to function as an initial filter of dropouts, compared with a direct recruitment model. CONCLUSIONS: This process holds several potentially useful lessons for investigators.

Alcoholism↗
PubMed2004

Prevalence of physical and sexual abuse among substance abuse patients and impact on treatment outcomes.

More than half of substance abusers entering addiction treatment report a history of physical or sexual abuse. It is unclear if such a history impacts treatment outcomes. This one-year follow-up study of 700 substance abusers sought to clarify the relationship between lifetime physical and/or sexual abuse and addiction treatment outcome to help address the specific needs of this population. To achieve this goal, baseline characteristics, no-show for treatment status, post-treatment clinical outcomes, and treatment history were studied for subjects with lifetime history of abuse (47.3%) versus without. Abused subjects, predominantly women, were significantly more impaired at baseline on clinical dimensions including family/social severity and psychiatric severity as measured by the Addiction Severity Index (ASI), and general level of functioning. The two groups endorsed different drugs as primary, with the abused group less frequently endorsing heroin and cocaine in favor of alcohol and polydrug use. Abused subjects reported more prior medical and psychiatric treatments. Abuse history was not a predictor of no-show for treatment. Over the 1-year follow-up, lifetime physical and/or sexual abuse was significantly associated with worse psychiatric status and more psychiatric hospitalizations and outpatient treatment despite receiving similar intensive addiction treatment.

Adult↗
PubMed2004

Decreased absolute amygdala volume in cocaine addicts.

The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.

Adult↗
PubMed2004

Validation of the Addiction Severity Index (ASI) for internet and automated telephone self-report administration.

This study assesses the convergent validity of Internet (Net) and interactive voice response (IVR) automated telephone self-report versions of the Addiction Severity Index (ASI) relative to the established, clinician-administered (CA) ASI. Eighty-eight subjects were recruited from an addiction treatment program to complete three ASI assessments. The mean correlation between composite scores obtained by Net and IVR and those obtained via clinician interview was.91 (range.81-.95). For History items, the mean correlation was.77 (range.14-1.00) and the mean kappa coefficient was.75 (range.46-1.00). The results demonstrated the validity of these self-report Net and IVR versions of the ASI. Self-report Net and IVR were rated as "very satisfactory" or "extremely satisfactory" by a majority of respondents for ease of use. Automation can reduce the labor costs associated with ASI administration and may facilitate longitudinal tracking of subjects from home.

Adult↗
PubMed2003

The relationship between cocaine craving, psychosocial treatment, and subsequent cocaine use.

OBJECTIVE: Regular measurement of craving during treatment for cocaine dependence can monitor patients' clinical status and potentially assess their risk for drug use in the near future. Effective treatment can reduce the correlation between craving and subsequent drug use by helping patients abstain despite high craving. This study examined the relationship between cocaine craving, psychosocial treatment, and cocaine use in the ensuing week. METHOD: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, which compared four psychosocial treatments for cocaine dependence, a three-item craving questionnaire was administered weekly to 449 patients to see whether it predicted cocaine use in the ensuing week. Cocaine use was assessed with self-reports and urine screening. RESULTS: With control for the previous week's cocaine use, a higher composite score on the craving questionnaire was associated with greater likelihood of cocaine use in the subsequent week; each 1-point increase on the composite score of the craving questionnaire increased the likelihood of cocaine use in the ensuing week by 10%. However, among patients who received individual plus group drug counseling, the treatment condition with the best overall cocaine use outcome, increased craving scores were not associated with greater likelihood of cocaine use in the subsequent week. CONCLUSIONS: A three-item cocaine craving questionnaire predicted the relative likelihood of cocaine use during the subsequent week. Moreover, the relationship between craving and subsequent cocaine use varied by treatment condition, suggesting that the most effective treatment in the study might have weakened the link between craving and subsequent use.

Adult↗
PubMed2003

Determining service variations between and within ASAM levels of care.

The American Society of Addiction Medicine (ASAM) Criteria Validity Study at Massachusetts General Hospital and Harvard Medical School randomized patients between programs in two levels of care. It therefore became critical to determine the extent to which programs met ASAM level of care (LOC) descriptions. Quantitative surveys (checklist) and qualitative case studies (field observation, key informant interviews) documented care variation within and between two ASAM LOCs in 12 substance abuse treatment units. These LOCs were: Level II (Intensive Outpatient Treatment) and Level III (Medically Monitored Residential Treatment). The Level II and Level III programs, as a group, met ASAM LOC criteria, but data showed major within-level variation by hours per day and number and type of skilled treatment services. Observational data suggest considerable within-level variation due to managed care and staff training. In multi-site PPC validity studies, it will be crucial to examine within-LOC variation and take into account payment sources and staff training when assessing patient outcomes.

Ambulatory Care↗
PubMed2003

Reliability of multidimensional substance abuse treatment matching: implementing the ASAM Patient Placement Criteria.

For meaningful adoption, the Patient Placement Criteria (PPC) of the American Society of Addiction Medicine (ASAM) will need adequate interrater reliability. In a decision analysis of the original PPC, we reduced potential sources of unreliability, mapped question items from clinical research instruments to each decision point, and programmed the item map as a computerized structured interview. Then, target videotapes from eight substance dependent adults who had been distributed by the algorithm into three levels of care (LOC) were independently scored by four raters who were blind as to ASAM LOC. The intraclass correlation coefficient for ASAM LOC assignment was .77. For all but two subscales of component instruments, values were above .70 and significant, indicating high interrater reliability. With these methods, excellent reliability is possible for complex decision trees, making it possible to improve the validity of the ASAM Criteria and similar complex hierarchical clinical protocols.

Decision Support Techniques↗
PubMed2003

Predictive validity of the ASAM Patient Placement Criteria for hospital utilization.

We tested the validity of the ASAM Patient Placement Criteria (PPC) using the first complete and reliable computerized implementation of these criteria. Adult U.S. veterans (N = 95) seeking substance abuse treatment were blindly assessed for level of care need according to the PPC but were naturalistically assigned by counselors to residential rehabilitation (Level III) without knowledge of the PPC recommendation. Analyses compared subjects across three levels of recommended care, based on the algorithm, for utilization outcomes of VA hospital admissions and bed days of care. Subjects who were mismatched to lesser level of care than recommended utilized nearly twice as many hospital bed-days over the subsequent year (F (2;92) = 3.88; p < .05); this was unrelated to differential pre-assessment chronicity. The computerized algorithm is a promising new tool for facilitating field trials of the validity of the ASAM Criteria. A comprehensive implementation is an important methodologic requirement. These preliminary results support predictive validity for the ASAM Criteria, in that mismatching may be associated with excessive hospital utilization.

Adult↗
PubMed2003

New constructs and assessments for relapse and continued use potential in the ASAM Patient Placement Criteria.

One area of intensive study in recent years in addiction research is the characterization and prediction of relapse risk. Given the growing list of findings and assessment tools in this area, in preparation for the second edition, revised volume of the Patient Placement Criteria (PPC) of the American Society of Addiction Medicine (ASAM), a workgroup of the Coalition for National Criteria was assigned the task of creating a revised conceptual organization for Dimension 5: Relapse/Continued Use Potential. The workgroup conducted a review of the previous Dimension 5 constructs and criteria, including a decision analysis of the previous Dimension 5 decision rules. Following that analysis, field data from the ASAM Criteria Validity Study at Massachusetts General Hospital and Harvard Medical School were analyzed from a large cohort of public and indigent patients in eastern Massachusetts. After determining the concurrent validity of the Dimension 5 decision rules and their limitations, the decision rules were rewritten to gain improved validity. This exercise revealed techniques that can and should be used to improve the discrimination of levels of care among all Dimensions. Finally, the workgroup expanded and refined the constructs that should comprise a revised Dimension 5. This revised list of constructs is sequential and hierarchical. It offers face validity on several levels of current basic and clinical research knowledge: behavioral pharmacology, behavioral psychology, learning theory and psychopathology. While the Second Edition-Revised volume of the ASAM PPC (PPC-2R) does not go so far as to propose final decision rules for Dimension 5 based on these new constructs, it does recommend pilot adoption of several new assessment tools for this dimension and provides the framework incorporating those constructs and assessments in the next complete PPC edition.

Adaptation, Psychological↗
PubMed2002

Retention in psychosocial treatment of cocaine dependence: predictors and impact on outcome.

This report describes retention in treatment in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (CCTS), a multi-site trial of four psychosocial treatments for 487 cocaine dependent patients. Younger, African-American, and unemployed patients were retained in treatment for fewer days than their counterparts. African-American patients who lived with a partner were retained in treatment for less time than if they lived alone. Higher psychiatric severity kept men in treatment longer but put women at risk for dropping out sooner. Patients who completed the full treatment used drugs less often than patients who dropped out, but outcome did not differ at each month. Patients in the drug counseling condition stayed in treatment for fewer days than patients in psychotherapy, but they were more likely to be abstinent after dropout. Patients with higher psychiatric severity were more at risk for continuing to use drugs after dropout.

Adult↗