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Director's Report to the National Advisory Council on Drug Abuse - February, 2005

Research Findings - Research on Behavioral and Combined Treatments for Drug Abuse

Extended Nortriptyline and Psychological Treatment for Cigarette Smoking

Dr. Hall and colleagues at the University of California, San Francisco, conducted a study to determine the effects of long-term antidepressant and psychological treatment for cigarette smoking. One hundred sixty smokers were randomly assigned to one of four treatment conditions in a 2 x 2 (nortriptyline vs. placebo by brief vs. extended treatment) design. All subjects received 8 weeks of a transdermal nicotine patch, five group counseling sessions, and active or placebo treatment. Interventions for subjects in brief treatment ended at this point. Subjects in extended treatment continued taking medication or placebo to week 52 and received an additional 9 monthly counseling sessions, with checkup telephone calls midway through each session. At week 52, point-prevalence abstinence rates with missing subjects imputed as smokers were 30% for placebo brief treatment, 42% for placebo extended treatment, 18% for active brief treatment, and 50% for active extended treatment. With missing subjects omitted, these rates were 32%, 57%, 21%, and 56%, respectively. Comprehensive extended treatments that combine medication and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature. Hall, S.M., Humfleet, G.L., Reus, V.I., Munoz, R.F. and Cullen, J. American Journal of Psychiatry, 161, pp. 2100-2107, 2004.

Utilizing Virtual Reality to Standardize Nicotine Craving Research: A Pilot Study

Traditional cue reactivity provides a methodology for examining drug triggers and stimuli in laboratory and clinical settings. However, current techniques lack standardization and generalization across research settings, i.e., the cues may lack ecological validity, tend to be presented out of context, and lack standardization across setting that limit the application of cue exposure practices. Improved methodologies using virtual reality (VR) cue reactivity extend previous research standardizing exposure to stimuli and exploring reactions to drug cues in a controlled VR setting. Improved methodologies include more complex cues involving combinations of social interactions, affective experiences, and physical cues to improve treatment generalization. In a controlled pilot trial, a VR cue exposure system with nicotine-dependent cigarette smokers was tested. It was hypothesized that VR-based smoking cues would elicit increased craving compared to VR neutral cues. Thirteen nicotine-dependent participants were allowed to smoke ad libitum then exposed to VR smoking and VR neutral cues and compared on craving intensity. VR smoking cues significantly increased craving compared to VR neutral cues. On average, craving intensity increased 118% during exposure to VR smoking cues. Implications for substance abuse research and treatment using VR to assess cessation and anticraving medications are discussed. Bordnick, P.S., Graap, K.M., Copp, H., Brooks, J., Ferrer, M. and Logue, B. Addictive Behaviors, 29, pp. 1889-1894, 2004.

Review of the Validity and Significance of Cannabis Withdrawal Syndrome

The authors review the literature examining the validity and significance of cannabis withdrawal syndrome. Converging evidence from basic laboratory and clinical studies indicates that a withdrawal syndrome reliably follows discontinuation of chronic heavy use of cannabis. Common symptoms are primarily emotional and behavioral, although appetite change, weight loss, and physical discomfort are also frequently reported. The onset and time course of these symptoms appear similar to those of other substance withdrawal syndromes. The magnitude and severity of these symptoms appear substantial, and these findings suggest that the syndrome has clinical importance. Diagnostic criteria for cannabis withdrawal syndrome are proposed. Budney, A.J., Hughes, J.R., Moore, B.A., and Vandrey, R. American Journal of Psychiatry, 161, pp. 1967-1977, 2004.

Motivational Interviewing With Personalized Feedback: A Brief Intervention for Motivating Smokers With Schizophrenia to Seek Treatment for Tobacco Dependence

This study examined whether motivational interviewing is effective in motivating smokers with schizophrenia or schizoaffective disorder to seek tobacco dependence treatment. Participants (N=78) were randomly assigned to receive a 1-session motivational interviewing intervention (MI), standard psychoeducational counseling (1-session), or brief advice only (5 min.). As hypothesized, a greater proportion of participants receiving the MI intervention contacted a tobacco dependence treatment provider (32%, 11%, and 0%, respectively) and attended the first session of counseling (28%, 9%, and 0%) by the one month follow-up compared with those receiving comparison interventions. Steinberg, M.L., Ziedonis, D.M., Krejci, J.A. and Brandon, T.H. Journal of Consulting and Clinical Psychology, 72, pp. 723-728, 2004.

The Marijuana Check-up: Reaching Users Who Are Ambivalent about Change

A brief intervention called the Marijuana Check-up (MCU) was designed to attract adult marijuana users who were experiencing adverse consequences, but who were ambivalent about change and would be unlikely to seek treatment. The objective of this study was to determine whether the MCU would reach the target population. Comparisons were made between those who enrolled in the MCU vs. those who were screened but failed to enroll based on demographic, drug use and stage of change variables. Comparisons were also made between participants in the MCU and participants in a concurrently offered treatment project that targeted users who wanted to quit. The MCU attracted and enrolled daily users of marijuana who experienced negative consequences but were ambivalent about making changes. The efficacy of the MCU in reducing marijuana use and associated consequences over the 12 months following the feedback sessions will be addressed in future papers. However, this study shows that marketing check-up interventions for marijuana users may help reduce barriers to engagement in drug abuse treatment. This low-burden modality may hold potential for attracting users, screening for problem use, resolving ambivalence and providing information on self-change and treatment options. Stephens, R.S., Roffman, R.A., Fearer, S.A., Willimas, C., Picciano, J.F. and Burke, R.S. Addiction, 99, pp. 1323-1332, 2004.

Improving Contingency Mangement Program for Addiction

Dr. Lamb and colleagues examined whether the effectiveness of contingency management interventions improves when contingencies are arranged in ways that improve the likelihood of all participants experiencing the available reward. In Study 1, smokers not planning to quit, were paid $0, 1, 3, 10, or 30 each day for 5 days for delivery of breath CO levels either < 4 ppm or below half the median of their baseline levels. Higher payment amounts and the easier target criterion resulted in a higher likelihood of participants meeting criterion. Once participants met the 4 ppm criterion, however, they often maintained this behavior even in the absence of payments for reduced breath CO levels. Study 2 examined the effectiveness of percentile schedules at shaping reduced breath CO levels. Percentile schedules shaped lower breath CO levels. The effectiveness of percentile schedules in shaping abstinence was tested in treatment seekers, and percentile schedules were found to be effective in shaping abstinence. Lamb, R.J., Kirby, K.C., Morral, A.R., Galbicka, G. and Iguchi, M.Y. Addictive Behaviors, 29, pp. 507-523, 2004.

Motivational Enhancement Therapy for Nicotine Dependence in Methadone-Maintained Pregnant Women

In this study, Dr. Haug and colleagues compared motivational enhancement therapy (MET) to standard-care practitioner advice for reducing smoking during pregnancy in a 2-group randomized design. Participants were 63 pregnant opioid-dependent smokers seeking substance abuse treatment, methadone maintenance, and prenatal care. At a 10-week follow-up, self-report and biological measures indicated no differences in smoking between the MET and standard-care groups. However, MET participants were more likely to have moved forward on the stage of change continuum than those in standard care. Intensive treatment for nicotine dependence, environmental interventions, and innovative harm reduction strategies are recommended to address the barriers to quitting observed in this population of pregnant women. Haug, N.A., Svikis, D.S. and Diclemente, C. Psychol Addict Behav. 18, pp. 289-292, 2004.

Correlates of Motivation to Quit Smoking in Methadone-Maintained Smokers Enrolled in a Smoking Cessation Trial

Investigators examined factors that may be associated with motivation to quit smoking in methadone-maintained persons. A sample of 255 smokers, enrolled in a smoking cessation research protocol, completed measures of their smoking motivation, smoking habit, quitting history, and intent to quit in the future. Analyses indicated that only number of cigarettes smoked per day and expectancies for success with smoking cessation were associated significantly with motivation to quit smoking. These results have implications for understanding motivational processes among methadone-maintained smokers and may help in the design of interventions that will assist this population with quitting smoking. Shadel, W.G., Stein, M.D., Anderson, B.J., Herman, D.S., Bishop, S., Lassor, J.A., Weinstock, M., Anthony, J.L. and Niaura, R. Addictive Behaviors, 20, pp. 295-300, 2005.

Treatment of Tobacco Use in an Inpatient Psychiatric Setting

This study examined delivery of tobacco cessation services in a smoke-free inpatient psychiatric setting. Medical records of 250 psychiatric inpatients were randomly selected and systematically reviewed. A total of 105 patients were identified as current smokers. Smokers evidenced statistically greater agitation and irritability compared with nonsmokers. None of the smokers received a diagnosis of nicotine dependence or withdrawal, and smoking status was not included in treatment planning for any patient. Nicotine replacement therapy was prescribed for 59 smokers. Smokers who were not given a prescription for nicotine replacement therapy were more than twice as likely as nonsmokers and smokers who were given a prescription for this therapy to be discharged from the hospital against medical advice. Only one smoker was encouraged to quit smoking. Psychiatric inpatients smoke at high rates, yet interventions to treat this deadly addiction are rare. Furthermore, not addressing nicotine withdrawal may compromise psychiatric care. Prochaska, J.J., Gill, P. and Hall, S.M., Psychiatric Services, 55, pp. 1265-1270, 2004.

Brief Motivational Intervention at a Medical Clinic Visit Reduces Cocaine and Heroin Use

Dr. Bernstein and colleagues at Boston University examined the effectiveness of a single, structured brief motivational intervention targeting cessation of drug use, conducted between peer educators and out-of-treatment cocaine and heroin users screened in the context of a routine medical visit. A randomized, controlled clinical trial was conducted in inner-city teaching hospital outpatient clinics with 3- and 6-month follow-up by blinded observers. Among the 23, 669 patients screened from 5/98-11/00, 1232 (5%) were eligible, and 1175 enrolled. Enrollees (mean age 38 years) were 29% female, 62% non-Hispanic black, 23% Hispanic, 46% homeless. Among those with drug positive hair at entry, the follow-up rate was 82%. The intervention group was more likely to be abstinent than the control group for cocaine alone (22.3% versus 16.9%), heroin alone (40.2% versus 30.6%), and both drugs (17.4% versus 12.8%), with adjusted OR of 1.51-1.57. Cocaine levels in hair were reduced by 29% for the intervention group and only 4% for the control group. Reductions in opiate levels were similar (29% versus 25%). This study shows that a brief motivational intervention in the medical clinic setting can reduce heroin and cocaine use. Peer interventionist may play an important role as physician extenders in a busy clinical environment, and this approach may enhance the screening, intervention, and referral of patients who use cocaine, heroin, and other drugs. Bernstein, J., Bernstein, E., Tassiopoulos, K., Heeren, T., Levenson, S. and Hingson, R. Drug and Alcohol Dependence, 77, pp. 49-59, 2005.

Computerized Drug Abuse Problem Assessment Helps Screen Older Adults in Primary Care

Dr. Nemes and her colleagues at Danya International, Inc., Silver Spring, Maryland, examined differences in responses of older adults (age 55 and above) and younger adults (ages 18-54) to the Drug Abuse Problem Assessment for Primary Care, (DAPA-PC), a computerized drug and alcohol screening instrument developed for primary care settings. Data were collected from a diverse population of 327 adults presenting for care at the George Washington University Medical Faculty Associates Clinic in Washington, D.C. Results indicated that rates of drug and alcohol abuse were similar in both groups. However, older adults were less likely than younger adults to perceive their drug use as problematic. This finding has serious implications for older adults, who tend to be underrepresented in treatment programs. There is a need for screening older adults and identifying those who may be at risk for substance abuse problems. Differences in responses to alcohol and drug assessments by age should be taken into consideration when designing screening instruments. The results of this study suggest that the DAPA-PC would provide a useful instrument for screening older adults in a primary care setting. Nemes, S., Rao, P.A., Zeiler, C., Munly, K., Holtz, K.D. and Hoffman, J. American Journal of Drug and Alcohol Abuse, 30(3), pp. 627-642, 2004.

Substance Use Histories in Patients Seeking Treatment for Controlled-Release Oxycodone Dependence

Drs. Potter, Weiss and colleagues at Harvard University, reviewed the medical records of 48 patients abusing Controlled Release oxycodone admitted consecutively to an inpatient detoxification unit to better understand the characteristics of treatment-seeking patients with problematic use of this medication. Patients were categorized according to the manner in which they initially received the drug: illicitly or by prescription legitimately for a medical condition. Fifteen of the 48 patients (31%) initially obtained a CR oxycodone prescription legitimately for a medical condition. While none of these 15 patients had a history of prior opioid misuse, they were more likely than illicit CR oxycodone users to report prior detoxifications as well as lower mean age of first alcohol use and first illicit drug use. These findings support the importance of comprehensive screening for all substance related disorders when opioid therapy for pain is considered. Potter, J.S., Hennessy, G., Borrow, J.A., Greenfield, S.F. and Weiss, R.D. Drug and Alcohol Dependence, 76, pp. 213-215, 2004.

Suicidal Behavior, Drug Use, and Depressive Symptoms

This 2-year prospective study of 470 patients following inpatient detoxification, examined factors associated with drug-related suicidal behavior using multivariable regression analyses. Suicidal behavior included suicidal ideation (SI) and suicide attempt (SA). Lifetime prevalence for SI was 28.5%, and for SA, 21.9%. During the 2-year follow-up, 19.9% of the sample endorsed suicidal ideation, and 6.9% reported a suicide attempt. Correlates of lifetime suicidal behavior included younger age, female, Hispanic, greater depressive symptoms, past sexual abuse, and problem sedative or alcohol use. Factors associated with suicidal behavior at follow-up included past suicidal behavior, more depressive symptoms, and more frequent benzodiazepine and alcohol abuse. These findings highlight the importance of addressing the recurrent suicide risk of patients with substance related disorder and frequent monitoring for changes in depressive symptoms and drug use. Wines, J.D., Saitz, R., Horton, N. J., Lloyd-Travaglini, C. and Samet, J. H. Drug and Alcohol Dependence, 76S, S21-S29, 2004.

Abstinent Unemployed Drug Abusers Taught Work Skills Via Computer That May Translate Into Better Paying Jobs

Participants in the therapeutic workplace program are taught typing and keypad data entry via a computerized self-paced learning program. Most began with few or no computer skills. Overall the eight participants who completed the training had a mean reading level of 9.4 grade years, had been heroin (100%) dependent and 75% also were alcohol and or cocaine dependent (75%). During the past three years 75% had been unemployed. Participants were required to submit a drug free urine test to enter the training program each day. Overall they took 51.48 training hours to acquire typing skills and 31.73 hours to learn keypad typing. Training occurred in one-minute trial blocks and participants were reinforced with pay for correct trials. These findings illustrate that even drug abusers with long histories of employment difficulties and less reading proficiency than a high school graduate could learn skills that could improve their "hireability" through this self-paced program. Dillon, E.M., Wong, C.J, Sylvest, C.E., Crone-Todd, D.E and Silverman, K. Substance Use and Misuse, 39, pp. 2325-2353, 2004.

New Stepped Care Methadone Treatment Combined with Behavioral Reinforcement Improves Employment Outcomes: Preliminary Findings

A new treatment that reinforces participants in methadone treatment for opiate dependence for treatment plan related behaviors including job seeking and job acquisition and which tapers them off methadone and discharges them from the clinic when they fail to engage in job seeking, shows promise for increasing job seeking behavior. Of those judged capable of working (not disabled), 93% achieved some form of employment (75% full time) during the times when the program was in effect. As this is not a randomized trial, care must be taken in interpreting these findings, but this study suggests that integrating tangible incentives for employment goals may improve employment outcomes in some drug abusers. Kidorf, M., Neufeld, K. and Brooner, R.K. Substance Use and Misuse, 39, pp. 2615-2238, 2004.

New Customized Employment Support Vocational Model Improves Employment Outcomes for Drug Abusers

A new vocational rehabilitation model that pairs drug abusers with a counselor for intense job placement and post-placement support with the goal of rapidly involving them in employment was preliminarily tested in 121 opiate users at two methadone programs. When compared with usual vocational counseling, participants were more likely to be in competitive employment or to have found any employment at all. These preliminary findings suggest this may be a promising new method for moving drug abusers into competitive employment. Staines, G.L., Blankertz, L., Magura, S., Bali, P., Madison, E.M., Spinelli, M., Horowitz, E., Guarino, H., Grandy, A., Fong, C., Gomez, A., Dimun, A. and Friedman, E. Substance Use and Misuse, 39, pp. 2261-2285, 2004.

Behavioral Therapies Can Be Effective in Treating Co-morbid Substance Abuse and Mood Disorders

Dr. Kathleen Carroll of Yale University reviewed the treatment literature regarding two classes of disorders that often co-occur: substance abuse and mood disorders. Focusing on three types of behavioral therapies—motivational interviewing, cognitive-behavioral therapies, and contingency management—Dr. Carroll evaluated the evidence for these therapies supporting treatment engagement, reduction in substance use, adherence to medications, and relapse prevention. She concludes that while these therapies have not been extensively tested among patients with co-morbid substance abuse and mood disorders, the preliminary evidence suggests that behavioral therapies can effectively treat this co-morbidity. Further, the evidence suggests that certain therapies may be better suited for different points in the treatment process. Given the high rate of co-morbid mood disorders among substance abusers, the positive preliminary results of behavioral treatments should inspire further development and testing of behavioral therapies targeting both disorders. Carroll, K.M. Behavioral Therapies for Co-occurring Substance Use and Mood Disorders. Biological Psychiatry, 56, pp. 778-784, November 2004.

Bipolar Disorder and Substance Abuse

Substance use disorders are over-represented in individuals with bipolar and bipolar spectrum disorders. Although awareness of this phenomenon has increased over the past 20 years, few empirically based treatment strategies have been developed for this challenging patient population. This review examines the relationship between bipolar and substance use disorders and treatment options that have been studied in this patient population. First, to examine the high prevalence rates of substance use disorders in individuals diagnosed with bipolar disorder, the common problems associated with establishing a bipolar disorder diagnosis in individuals who abuse substances, the possible explanations for the frequent coexistence of bipolar and substance use disorders, and the negative effect of substance abuse on the course of and treatment outcomes for bipolar disorder. The review then focuses on treatment approaches for this patient population, including integrated group therapy for co-occurring bipolar and substance use disorders and pharmacotherapies that target both disorders. Finally, it presents suggestions for medications that might be tested for their efficacy in treating both disorders in specific subgroups of patients with bipolar and substance use disorders. Levin, F.R. and Hennessy, G. Bipolar Disorder and Substance Abuse. Biol. Psychiatry, 56, pp. 738-748, 2004.

Treatment of Depression in Patients with Opiate Dependence

Depression is common among opiate-dependent patients and has been associated with worse prognosis. This article reviews the literature on treatment of depressive disorders and symptoms among patients with opiate dependence. Depression bears a complex relationship to opiate dependence and may represent an independent disorder or may be engendered by psychosocial stress or toxic and withdrawal effects of drugs. Primary treatments for opiate dependence (e.g., methadone or buprenorphine maintenance or residential treatment) are associated with substantial improvements in depression. Studies of antidepressant medications have produced mixed results, some positive but more negative. It is not clear what accounts for these differences, and more research is needed to determine how to select opiate-dependent patients most likely to benefit from antidepressants. Fewer studies have examined psychosocial or behavioral interventions, but some of these also show promise. The data suggest a stepped model of care in which depression is evaluated and observed during the outset of treatment for opiate dependence and if it does not improve, specific psychosocial interventions or antidepressant medications tried. Research is needed on such integrated models of care and treatment algorithms to determine their efficacy and cost effectiveness. Nunes, E.V., Sullivan, M.A. and Levin, F.R. Treatment of Depression in Patients with Opiate Dependence. Biol. Psychiatry, 56, pp. 793-802, 2004.

Treatment of Cocaine-alcohol Dependence with Naltrexone and Relapse Prevention Therapy

This study evaluates whether patients with cocaine-alcohol dependence might benefit from naltrexone (NTX) pharmacotherapy when delivered in conjunction with psychotherapy. Eighty outpatients meeting DSM-IV criteria for alcohol and cocaine dependence were randomly assigned to receive NTX (placebo or 50 mg/d) combined with psychotherapy (Relapse Prevention [RP] or Drug Counseling [DC]) for twelve weeks. It was hypothesized that the skills training focus of RP therapy, in combination with NTX 50 mg/d, would produce greater reductions in cocaine and alcohol use. Outcome measures included self- and objective reports of substance use, treatment retention, medication compliance, and adverse effects. During the first four weeks of treatment, the percentage of cocaine-positive urine screens was significantly lower for those receiving RP therapy (22%) than those receiving DC (47%); however, this difference subsequently diminished. No medication effects were found. All groups reported less alcohol use at the end of treatment. Treatment retention was the same among the groups, with about 33% of the subjects completing all twelve weeks of treatment. The active medication group showed better medication compliance, while the number of adverse events was low overall and not significantly different by group. NTX at 50 mg/d did not reduce cocaine or alcohol use. These findings stand in contrast to previously reported positive findings for NTX and RP in patients with a single diagnosis of cocaine dependence. Schmitz, J.M., Stotts, A.L., Sayre, S.L., DeLaune, K.A. and Grabowski, J. Treatment of Cocaine-alcohol Dependence with Naltrexone and Relapse Prevention Therapy. Am. J Addict, 13, pp. 333-341, 2004.


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