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National Institute on Drug Abuse

Director's Report to the National Advisory Council on Drug Abuse

February, 1999

Research Findings

Clinical and Services Research

Open Trial of Bupropion to Treat ADHD in Adolescents with Substance Use Disorders and Conduct Disorder.

Dr. Riggs and colleagues at the University of Colorado School of Medicine assessed the efficacy of bupropion to treat attention deficit hyperactivity disorder (ADHD) in adolescent males diagnosed with comorbid conduct and substance use disorders. The primary aim was to treat the ADHD and thereby indirectly reduce drug use and other behavior problems. Preliminary data indicate a reduction in ADHD symptomatology, antisocial behavior and level of drug abuse. Riggs, P.D., Leon, S.L., Mikulich, S.K. and Pottle, L.C. J. Am. Acad. Child Adolesc. Psychiatry, 37(12), pp. 1271-1278, 1998.

Fluoxetine Treatment of Depressive Disorders in Methadone Maintained Opioid Addicts

Drs. Petrakis, Carroll, Kosten, and Rounsaville at Yale University in Connecticut evaluated the efficacy of fluoxetine as a treatment for depression in a population of methadone maintained opioid addicts. Forty-four methadone maintained opioid addicts with depression received either fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use was unchanged from pre-treatment to endpoint. Data analyses were conducted on a subsample of subjects with the most severe depression but there was no medication effect on either the depressive symptoms or on cocaine use. The findings suggest that fluoxetine is not effective in treating depression or cocaine use in this population. Drug and Alcohol Dependence, 50(3), pp. 221-226, 1998.

Superior Efficacy of Cognitive-Behavioral Therapy for Urban Crack Cocaine Users When Compared to 12 Step Facilitation: Main and Matching Effects

Drs. Maude-Griffin, Hohenstein, Humfleet, Reilly, Tusel, and Hall at the University of California and the San Francisco Veterans Affairs Medical Center evaluated the efficacy of manualized cognitive-behavioral therapy (CBT) and 12-step facilitation (12SF) in treating cocaine abuse by randomly assigning 128 subjects (126 males and 2 females; 80% African American; 84% unemployed; 75% homeless; 82% had a comorbid psychiatric disorder) to one of the two treatment conditions. In each treatment condition, subjects attended 3 group therapy sessions and one individual counseling session each week for 12 weeks. Patient-treatment matching effects such as depression history, abstract reasoning ability, religious beliefs, drug use severity, and disease model beliefs, were evaluated. The study showed that the CBT participants were more likely to achieve 4 consecutive weeks of abstinence from cocaine than participants in the 12SF group (44% vs. 32%) verified through urine toxicology. Patients with depression and those with high abstract reasoning scores were more likely to benefit from the CBT than the 12SF. Drug use severity and belief in a disease model did not interact significantly with treatment condition to predict continuous abstinence. In this study African Americans with strong religious beliefs appeared to benefit more from 12SF than the CBT in achieving cocaine abstinence. This study is the first to demonstrate the superior efficacy of CBT for cocaine abuse when compared to another active psychotherapy. In addition, this study provides support for patient-treatment matching since the results suggest that both CBT and 12SF may be differentially effective for different subgroups of cocaine abusing patients. J. of Counseling and Clinical Psychology, 66(5), pp. 832-837, 1998.

Group Cognitive-Behavior Therapy For Dual-Diagnosis Women

Dr. Lisa Najavits developed a manualized treatment specifically adapted to the clinical needs of women with comorbid post-traumatic stress disorder (PTSD) and substance use disorder. No effective treatment has been identified for this substantial subpopulation of female drug abusers who also experience PTSD (33-59%). Outcome results on 17 women who completed the protocol treatment showed significant improvements in substance use, trauma-related symptoms, suicide risk, suicidal thoughts, social adjustment, family functioning, problem solving, depression, cognitions about substance use, and didactic knowledge related to the treatment. Results were based on assessments at pre-treatment, during treatment, post-treatment, and 3-month follow-up. The data suggest that women substance abusers with PTSD are highly responsive and able to show marked improvements when provided with a treatment that is adapted to their needs. Najavits, L.M., Weiss, R.D., Shaw, S.R., and Muenz, L.R. "Seeking Safety": Outcome of a New Cognitive-Behavioral Psychotherapy for Women with Posttraumatic Stress Disorder and Substance Dependence. Journal of Traumatic Stress, 11, pp. 437-56, 1998.

Cotinine: Effects with and Without Nicotine

The purpose of this study was to examine the effects of the metabolite of nicotine, cotinine, in comparison to the effects of the nicotine patch, and a combination thereof during cigarette abstinence. More specifically, this study examined the effects of cotinine on physiological measures, subjective measures assessing craving, withdrawal symptoms and mood, and performance measures. A between-subject, 2 x 2 factorial design was used, with the daily administration of a 15-mg nicotine patch (Nicotrol) versus placebo patch as one factor and 80 mg of oral cotinine fumarate versus placebo drug as the other factor. Baseline measures were obtained while the subjects smoked cigarettes on an ad lib basis for 1 week. Subjects (n=106) were then randomly assigned to one of four treatment conditions and for the next 14 days were required to be abstinent from cigarettes and take the study drugs. Cotinine administration, with or without nicotine patch, produced serum cotinine concentrations 3-4 times higher than during ad lib smoking. Results showed a reduction of self-reported tobacco withdrawal symptoms using the nicotine patch alone. Cotinine alone had no effect on withdrawal symptoms. However, when nicotine patch was combined with cotinine, the beneficial effect of the nicotine patch on withdrawal symptoms was absent. Therefore, cotinine appears to antagonize the effects of nicotine in the alleviation of withdrawal symptoms at concentrations higher than that attained from normal smoking. This effect does not appear to be mediated by changes in nicotine disposition. (author abstract) Hatsukami, D., Pentel, P.R., Jensen, J., Nelson, D., Allen, S.S., Goldman, A. and Raphael, D. Cotinine: Effects with and Without Nicotine. Psychopharmacology, 135, pp. 141-150, 1998.

Methylphenidate Treatment for Cocaine Abusers with Adult Attention-Deficit/ Hyperactivity Disorder: A Pilot Study

Attention-deficit/hyperactivity disorder (ADHD) is common among cocaine abusers seeking treatment. This open trial was carried out to assess the efficacy of sustained-release methylphenidate for the treatment of cocaine abuse among individuals with ADHD. Twelve patients who met DSM-IV diagnostic criteria for adult ADHD and cocaine dependence were entered into a 12-week trial of divided daily doses of sustained-release methylphenidate ranging from 40 to 80 mg. In addition to the pharmaco-therapy, patients also received individual weekly relapse prevention therapy. Individuals were assessed weekly for ADHD symptoms; vital signs and urine toxicologies were obtained 3 times a week. Of the 12 patients entered, 10 completed at least 8 weeks of the study and 8 completed the entire study. Using both a semistructured clinical interview and a self-report assessment, patients reported reductions in attention difficulties, hyperactivity, and impulsivity. Self-reported cocaine use and craving decreased significantly. More importantly, cocaine use, confirmed by urine toxicologies, also decreased significantly. These preliminary data suggest that under close supervision, the combined intervention of sustained-release methylphenidate and relapse prevention therapy may be effective in treating individuals with both adult ADHD and cocaine dependence. (author abstract) Levin, F.R., Evans, S.M., McDowell, D.M., and Kleber, H.D. Methylphenidate Treatment for Cocaine Abusers with Adult Attention-Deficit/Hyperactivity Disorder: A Pilot Study. Journal of Clinical Psychiatry, 59, pp. 300-305, 1998.

Chronic Disulfiram Treatment Effects on Intranasal Cocaine Administration: Initial Results

Simultaneous abuse of cocaine and alcohol is common. Alcohol decreases negative stimulant effects and potentiates "high." Disulfiram (Antabuse) is being studied in outpatient trials as a cocaine pharmacotherapy with the rationale that inability to modulate cocaine effects with alcohol may decrease cocaine use. Authors examined the interaction of disulfiram and cocaine in a randomized, double-blind, placebo-controlled study where subjects were chronically treated with disulfiram and then participated in intranasal cocaine administration studies. Disulfiram 250 mg/day treatment significantly increased plasma cocaine concentrations (p = .013), heart rate (cocaine 1 mg/kg, p = .046), and systolic (cocaine 2 mg/kg p = .003) and diastolic (cocaine 2 mg/kg, p = .022) blood pressure. "High" and "nervous" ratings were nonsignificantly increased. The combination of "high" with increased anxiety in the context of inability to lessen negative effects with alcohol may be an effective treatment in selected patients. The significant pharmacokinetic interaction must be considered in the decision regarding use of disulfiram. (author abstract) McCance-Katz, E.F., Kosten, T.R., Jatlow, P. Chronic Disulfiram Treatment Effects on Intranasal Cocaine Administration: Initial Results. Biological Psychiatry, 43, pp. 540-543, 1998.

Amantadine Hydrochloride is Effective Treatment for Cocaine Dependence

Amantadine hydrochloride, a dopamine agonist, seems conceptually suitable as a candidate for cocaine dependence treatment. Authors report on a 16-week double-blind, randomized, placebo-controlled rapid evaluation of amantadine (100 mg bid) trial with 69 cocaine dependent subjects (34 amantadine, 35 placebo) in a community-based clinic in LA. Matrix Model counseling served as the psychosocial base for the trial. Subjects attended clinic 3 times per week (M,W,F) to provide data (urine samples, questionnaires) and to receive counseling (90 minute groups). Dependent variables were urine toxicology results as compiled by the Treatment Effectiveness Score (i.e., the number of "clean" urines for each subject) and Joint Probability at 8 and 16 weeks (i.e., number of subjects providing "clean" urines divided by number of subjects in that condition at that point). Though TES analyses fall just short of significance for amantadine (MA=16.0 "cleans"; MP=10.9 "cleans"; P<.08), significantly fewer amantadine subjects used cocaine at weeks 8 (A=13/34 subjects (0.38); P=5/35 subjects (0.14); z=2.27, p=.01) and 16 (A=9/34 subjects (0.27); P=3/35 subjects (0.09); z=2.27, p=0.01). Authors conclude that amantadine is sufficiently promising in efficacy to warrant further evaluation with large scale clinical trials. (author abstract) Shoptaw, S., Ling, W., Kintaudi, K., Rawson, R.A. Amantadine Hydrochloride is Effective Treatment for Cocaine Dependence. College on Problems of Drug Dependence, 60th Annual Scientific Meeting, Scottsdale, AZ , p. 132, 1998.

Several 'Endophenotypes' Have Been Described as Possible Markers for Drug Abuse Vulnerability

William G. Iacono and colleagues at the University of Minnesota have reported psychophysiological measures associated with increased risk for drug abuse. One example is based on "preception" -- ability to take advantage of the predictability of an aversive event to diminish its psychological impact; the second, on "antisaccades" -- the ability to generate a saccade in the direction opposite to an abrupt movement of tracking target. In the preception experiment, subjects watched the sweep hand of a clock and were told that a loud, unpleasant noise would be heard at infrequent times. Sometimes these blasts would be predictable by appearance of a warning stimulus; other times there would be no warning. Skin Conductance Responses (SCRs) and Heart Rates (HRs) were measures of how well the subjects made use of the warning information. Results showed that poor modulators -- individuals whose SCRs were higher for the predictable loud noises and whose HRs did not differentiate predictable from non-predictable -- had significantly more symptoms of alcohol and nicotine dependence. These results were interpreted as biologically based support for the theory that individuals at risk for substance dependence have poor inhibitory control related to a dysfunctional Behavioral Inhibition System (BIS). Taylor, J., Carlson, S.R., Iacono, W.G., Lykken, D.T., and McGue, M. Individual Differences in Electrodermal Responsivity to Predictable Aversive Stimuli and Substance Dependence. Psychophysiology, 36, pp. 1-6, 1998. In the antisaccade experiment, subjects are required to make an eye movement in the direction opposite to a moving target which is contrary to natural tendency. Those who are less successful are said to have a more faulty control on inhibitory mechanisms. The results showed a higher error rate in this task among "high risk" 17 year-old boys compared to "low risk" boys. (High and low risk are defined as to whether fathers did or did not have a diagnosis of illicit drug abuse or dependence with co-morbid antisocial personality disorder). Additionally MZ twins discordant for drug abuse/dependence were nevertheless concordant for high error rates, suggesting a genetically based susceptibility for this deficit independent of diagnosis. Iacono, W. G. Identifying Psychophysiolgical Risk for Psychopathology: Examples from Substance Abuse and Schizophrenia Research. Psychophysiology, 35, pp.1-17, 1998.

Lowered P300 Electrical Evoked Responses were Associated with Drug Abuse Vulnerability

Iacono and colleagues demonstrated that the commonly reported electrical evoked response potentials (ERP) --P300-- to rare stimuli had a major genetic component because the amplitude was correlated by as much as .87 between one hemisphere of a monozygotic twin to the other hemisphere of the co-twin. Several studies in Iacono's lab showed that a reduced amplitude of this ERP was found in individuals with substance abuse problems or those at risk. In one study, there were significantly more cases of alcohol, illicit drug, and nicotine dependence among individuals with small P300 amplitudes than among the group with large amplitudes. Secondly, lower P300 amplitudes were reported in men who had alcohol abuse either alone or co-morbid with antisocial personality disorder, drug dependence, or both (smallest amplitude). Lower amplitudes were also reported in 17 year-old boys whose fathers had these diagnoses. Finally, there were lower P300 amplitudes in 17 year-old boys who subsequently (3 years later) developed an illicit drug abuse/dependence or nicotine dependence. Iacono, W.G. Identifying Psychophysiolgical Risk for Psychopathology: Examples from Substance Abuse and Schizophrenia Research. Psychophysiology, 35, pp.1-17, 1998.

Group Counseling Versus Individualized Relapse Prevention Aftercare Following Intensive Outpatient Treatment for Cocaine Dependence: Initial Results

Ninety-eight male cocaine-dependent patients who completed an intensive outpatient program were randomly assigned to either standard group counseling (STND) or individualized relapse prevention (RP) aftercare. Heavier cocaine and alcohol use and low self-efficacy predicted more cocaine use during the intensive outpatient treatment phase of the study, whereas lifetime diagnoses of alcohol dependence, major depression, and anxiety disorder predicted less cocaine use. Rates of complete abstinence during the 6-month study period were higher in STND than RP, whereas RP was more effective in limiting the extent of cocaine use in those who used during Months 1-3. Matching analyses indicated patients who failed to achieve remission from cocaine use during intensive outpatient treatment and those with a strong commitment to abstinence did better in RP than in STND, whereas patients less committed to abstinence did better in STND than RP. McKay, J.R., Alterman, A.I., Cacciola, J.S., Rutherford, M.J., O_Brien, C.P., and Koppenhaver, J. Journal of Counseling and Clinical Psychology, 66(5), pp. 778-788, 1997.

Predictors of Participation in Aftercare Sessions and Self-Help Groups Following Completion of Intensive Outpatient Treatment for Substance Abuse

The goals of this study were to identify predictors of greater participation in aftercare treatment sessions and self-help groups during the first 3 months following completion of a 4-week intensive outpatient rehabilitation (IOP) program. The subjects were 138 male veterans who a) met DSM-III-R criteria for lifetime diagnoses of both alcohol and cocaine dependence (n=67), alcohol dependence only (n=48) or cocaine dependence only (n=23); b) completed an IOP program; and c) expressed a desire to enter a formal aftercare program. Analyses examined relationships between predictor variables from five different domains and number of aftercare sessions and self-help groups attended in the last week of each month of the follow-up period. Of the predictor variables that were examined, only remission from cocaine and alcohol dependence during IOP and higher AIDS risk behavior scores in the prior 6 months contributed independently to the prediction of greater participation in aftercare. Further analyses identified several variables that were differential predictors of participation in individualized relapse prevention aftercare versus standard 12-step focused group aftercare. More years of cocaine use, greater current legal problems, and a lack of current alcohol dependence predicted greater self-help participation at the level of a trend. Remission from substance use dependence during IOP may be an important criterion for moving to the next level of care. However, the results of this study also look at factors present during the course of aftercare. McKay, J.R., McLellan, A.T., Alterman, A.I., Cacciola, J.S., Rutherford, M.J., and O_Brien, C.P. J. Stud. Alcohol, 59, pp.152-162, 1998.

Using State Information Systems for Drug Abuse Services Research

Political and social demands for effective and cost-effective drug and alcohol treatments challenge public policy makers and services researchers to assess provider performance, monitor patient outcomes, and document effectiveness and cost-effectiveness of care. The information systems built and maintained by public health authorities are an under used source of data on provider performance, patient characteristics, treatment completion, readmission rates, treatment outcomes, and costs of care. The Maine, Massachusetts, and Ohio substance abuse information systems were used to demonstrate the benefits and pitfalls of state substance abuse databases to study the organization, costs, and cost-effectiveness of publicly funded treatment services. McCarty, D., McGuire, T.G., Harwood, H.J. and Field, T. American Behavioral Scientist, 41(8), pp. 1090-1106, 1998.

Service-level Costing of Drug Abuse Treatment

A methodology is developed for estimating the cost of delivering specific substance abuse treatment services. Based on data from 13 programs, it was estimated that the average cost of residential treatment is $2,773 per patient per month and outpatient treatment costs an average of $636 per patient per month. Data are presented on the cost per patient per month for individual treatment and nontreatment services, average number of services, costs per unit of service, and intensity of services. In addition to their applications to insurance benefit cost estimation and as an aid in the design of cost-effective treatment, these data illustrate the costing of best practice adolescent treatment consistent with a Center for Substance Abuse Treatment (CSAT) Treatment Improvement Protocol. Anderson, D.W., Bowland, B.J., Cartwright, W.S. and Bassin, G. Journal of Substance Abuse Treatment, 15(3), pp. 201-211, 1998.

Mapping-Enhanced Drug Abuse Counseling Urinalysis Results in the First Year of Methadone Treatment

Urinalysis (UA) tests for opiates and cocaine were obtained over a 12-month period for a total of 155 long-term patients who participated in treatment in one of three urban methadone centers. At admission, patients were randomly assigned to "node-link mapping" (n=82) or "standard" (n=73) counseling treatment. Node-link mapping is a strategy for visually representing interrelationships between patients' ideas, feelings, and experiences. These multirelational maps are developed (usually by counselors) during individual and group counseling sessions to clarify patients' issues and problems. The results revealed that (a) mapping patients had significantly fewer opiate-positive UAs during months 2-6 of treatment and (b) session attendance was a significant predictor of cocaine-positive UAs over months 2-12 for mapping patients. The findings suggest that mapping-enhanced counseling is an effective method for improving outcomes during the first six months of treatment. Dees, S.M., Dansereau, D.F., and Simpson, D.D. Journal of Substance Abuse Treatment, 14(1), pp. 45-54, 1997.

Current Approaches to Drug Treatment for Women Offenders

Treatment approaches at eight corrections- and community-based programs in New York City and Portland, Oregon are reviewed. Data were obtained from life history interviews conducted with 60 women and from observation of treatment. Drug abuse treatment programs for women offenders employ a range of therapeutic interventions to address drug use and criminality. Recently, programs have begun to address victimization experiences as an integral if not central feature of women's drug use and participation in illegal activities. Programs have tailored treatment approaches for women offenders by offering incest and domestic violence survivor groups, assigning therapeutic rather than punitive sanctions, and training corrections staff to support treatment goals. Welle, D., Falkin, G.P., Jainchill, N. Journal of Substance Abuse Treatment, 15(2), pp. 151-163, 1998.

Predicting Drug Treatment Entry Among Treatment-Seeking Individuals

This study examines factors contributing to treatment entry in a sample of 276 drug abusers who actively sought referral to drug treatment. At 6 months after referral to a treatment program, about 62% had entered treatment. Treatment-entry and non-entry subjects did not differ in socio-demographics (age, gender, race/ethnicity, education), type of drug use, or years of use. Legal coercion was found to be an effective factor promoting treatment entry. Those having prior successful treatment experience were also more likely to re-enter treatment. However, those with more severe problems (drug related and other) seemed less likely to enter treatment, suggesting that psychological distress and family problems may undermine motivation to follow through on treatment referral. The findings also indicate that attention is needed to improve treatment access and to address related issues such as eligibility criteria, waiting list alternatives, and transportation. Hser, Y.I., Maglione, M., Polinsky, M.L., and Anglin, M.D. Journal of Substance Abuse Treatment, 15(3), pp. 213-220, 1998.

Management of Adults Recovering From Alcohol or Other Drug Problems

This study offers a practical approach to relapse prevention in the primary care setting for physicians who encounter relapse to drug or alcohol use in patients recovering from drug disorders. Working within a supportive patient-physician relationship, the primary care physician can help recovering patients decrease their susceptibility to relapse by employing strategies based on effective drug abuse treatment. Drawing on the therapeutic relationship and skills they already possess, primary care physicians can have an important, productive, and satisfying role in the long-term management of patients in recovery from alcohol or other drug problems. Friedmann, P.D., Saitz, R., and Samet, J.H. JAMA, 279, pp. 1227-1231, 1998.

Organizational Correlates of Access to Primary Care and Mental Health Services in Drug Abuse Treatment Units

Organizational factors were found to be associated with access to primary care and mental health services in drug abuse treatment. Findings were based on a national probability survey of 618 outpatient drug abuse treatment programs in 1995. It was found that publicly-funded programs, programs with more human resources, and methadone programs delivered more primary care services. Greater access to mental health services was found in publicly-funded programs, Joint Commission on Accreditation of Health Care Organizations-accredited programs, nonmethadone programs, and programs with more staff psychiatrists or psychologists delivered more mental health services. Friedmann, P.D., Alexander, J.A. and D'Aunno, T.A. Elsevier Science Inc., 1998.

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