Research Findings - Research on Behavioral and Combined Treatments for Drug Abuse
Self-Efficacy and Depression as Mediators of the Relationship between Pain and Antiretroviral Adherence
The goals of this study were to examine the association between pain and antiretroviral adherence and to estimate the mediating effect of adherence self-efficacy and depression symptom severity. Surveys using audio computer-assisted self-interview were conducted among 70 HIV-infected current and former drug users enrolled in a methadone program. Researchers assessed antiretroviral adherence, adherence self-efficacy, depression symptoms, and pain. Participants reporting pain were 87% less likely to be classified as adherent compared to those without pain. Results indicated that neither adherence self-efficacy nor depression symptom severity fully mediated the relationship between pain and adherence. HIV providers should recognize the potential impact of pain on antiretroviral adherence among current and former drug users. Berg KM, Cooperman NA, Newville H, Arnsten JH. Self-efficacy and depression as mediators of the relationship between pain and antiretroviral adherence. AIDS Care. 2009;21(2):244-8.
A Deposit Contract Method to Deliver Abstinence Reinforcement for Cigarette Smoking
Dr. Jesse Dallery and colleagues from the University of Florida conducted this pilot study to test the feasibility and effects of a potentially cost-effective method to deliver an abstinence-reinforcement intervention for smoking cessation. Eight smokers were randomly assigned to a deposit contact of $50.00 or to a no-deposit group. Using a reversal design, participants could recoup their deposit (deposit group) or earn vouchers (no-deposit group) for smoking reductions and abstinence during treatment phases. Treatment was delivered via a novel Internet-based method to monitor smoking status. There were no clear differences in rates of abstinence between the deposit and no-deposit groups. In the deposit group, 65% of the samples were negative, and in the no-deposit group, 63% of the samples were negative. Although equivalent decreases in breath CO and abstinence were observed during treatment in both groups, $178.50 in vouchers were distributed to participants in the no-deposit group, whereas a small surplus remained in the deposit group. The authors conclude that a deposit contract method may represent a cost-effective model to deliver abstinence reinforcement for cigarette smoking, however, this method should be tested with a larger sample. Dallery J, Meredith S, Glenn IM. A deposit contract method to deliver abstinence reinforcement for cigarette smoking. Journal of Applied Behavior Analysis, 2008;41(4):609-15.
Lack of an Inverse Relationship between Duration of Untreated Psychosis and Cognitive Function in First Episode Schizophrenia
This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. Researchers discovered that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. The results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable. Goldberg TE, Burdick KE, McCormack J, Napolitano B, Patel RC, Sevy SM, Goldman R, Lencz T, Malhotra AK, Kane JM, Robinson DG. Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia. Schizophr Res. 2009;107(2-3):262-6. Epub 2008 Nov 29.
Persistence of Virological Benefits Following Directly Administered Antiretroviral Therapy among Drug Users: Results from a Randomized Controlled Trial
Although directly administered antiretroviral therapy (DAART) has demonstrated impressive biological benefits compared with self-administered therapy (SAT) among drug users, the persistence of DAART after transition to SAT has not been examined. The authors conducted a community-based, prospective, randomized controlled trial of 6 months of DAART compared with SAT. The primary outcome was the proportion of subjects who achieved virological success at 6 months post-intervention (defined as either a 1.0 log10 reduction from baseline or HIV-1 RNA <400 copies per milliliter). Secondary outcomes included the change from baseline in HIV-1 RNA and CD4 lymphocyte count. Results suggest that the DAART (n = 88) and SAT (n = 53) arms did not differ on virological success (DAART 58.0% vs. SAT 56.6%, P = 0.64), mean reduction in log10 HIV-1 RNA (-0.79 vs. -0.31 log10 copies/mL, P = 0.53), or mean change in CD4 lymphocyte count (+60.2 vs. -15.4 cells/mL, P = 0.12). In the multivariate analysis, only high levels of social support significantly predicted virological success. These data, the first emerging from a randomized controlled trial of DAART among active drug users, are interesting in that they fail to show the persistence of the DAART intervention at improving virological outcomes. Additional strategies are needed to ensure that treatment benefits persist following the cessation of DAART. Maru DS, Bruce RD, Walton M, Springer SA, Altice FL. Persistence of virological benefits following directly administered antiretroviral therapy among drug users: results from a randomized controlled trial. J Acquir Immune Defic Syndr. 2009;50(2):176-81.
The Role of Anxiety Sensitivity and Difficulties in Emotion Regulation in Posttraumatic Stress Disorder among Crack/Cocaine Dependent Patients in Residential Substance Abuse Treatment
Current research suggests the importance of anxiety sensitivity (AS) in the risk for posttraumatic stress disorder (PTSD), and a growing body of research has demonstrated that difficulties in emotion regulation may also play a role. This study examined the unique relationships between AS dimensions, difficulties in emotion regulation, and a probable PTSD diagnosis among a sample of inner-city crack/cocaine dependent patients in residential substance abuse treatment. Probable PTSD participants exhibited higher levels of the AS dimension of social concerns and emotion regulation difficulties. In addition, difficulties in emotion regulation reliably distinguished probable PTSD participants from non-PTSD participants above and beyond both anxiety symptom severity and the AS dimension of social concerns. Further, social concerns did not account for unique variance when difficulties in emotion regulation were entered into the model. Results provide support for the central role of difficulties in emotion regulation relative to AS dimensions in the prediction of PTSD within a crack/cocaine dependent population. McDermott MJ, Tull MT, Gratz KL, Daughters SB, Lejuez CW. The role of anxiety sensitivity and difficulties in emotion regulation in posttraumatic stress disorder among crack/cocaine dependent patients in residential substance abuse treatment. J Anxiety Disord. 2009; Jan 20; [Epub ahead of print].
Adolescent Change Language Within a Brief Motivational Intervention and Substance Use Outcomes
Homeless adolescents who used alcohol or illicit substances but were not seeking treatment (n = 54) were recorded during brief motivational interventions. Adolescent language during sessions was coded on the basis of motivational interviewing concepts (global ratings of engagement and affect, counts of commitment to change, statements about reasons for change, and statements about desire or ability to change), and ratings were tested as predictors of rates of substance use over time. Results indicate that statements about desire or ability against change were strongly and negatively predictive of changes in substance use rates (days of abstinence over the prior month) at both 1- and 3-month post-baseline assessment. Statements about reasons for change were associated with greater reductions in days of substance use at 1-month assessment. Commitment to change language was not associated with outcomes. The investigators conclude that specific aspects of adolescent speech in brief interventions may be important in the prediction of change in substance use behaviors, and that these relationships should be examined within larger samples and other clinical contexts. Baer JS, Beadnell B, Garrett SB, Hartzler B, Wells EA, Peterson PL. Adolescent change language within a brief motivational intervention and substance se outcomes. Psychology Addict Behav. 2008; 22(4):570-5.
A Randomized Controlled Trial of Multidimensional Family Therapy for Young Adolescent Substance Abuse: Twelve-Month Outcomes
Research has established the dangers of early onset substance use for young adolescents and its links to a host of developmental problems. Specialized interventions that target known risk and protective factors during this critical developmental period are needed. This controlled trial (n = 83) provided an experimental test comparing multidimensional family therapy (MDFT) and a peer group intervention with young teens. Participants were clinically referred, of low income, and mostly ethnic minority adolescents (average age = 13.73 years). Treatments were manual guided, lasted 4 months, and were delivered by community agency therapists. Adolescents and parent assessments took place at intake, 6-weeks post-intake, discharge, and 6 and 12 months following treatment intake. Latent growth curve modeling analyses demonstrated the superior effectiveness of MDFT over the 12-month follow-up in reducing substance use (effect size: substance use frequency, d = 0.77; substance use problems, d = 0.74), delinquency (d = 0.31), and internalized distress (d = 0.54), and in reducing risk in family, peer, and school domains (d = 0.27, 0.67, and 0.35, respectively) among young adolescents. Liddle HA, Rowe CL, Henderson CE, Dakof GA, Greenbaum PE. Multidimensional family therapy for young adolescent substance abuse: twelve-month outcomes of a randomized controlled trial. J Consult Clin Psychol. 2009;77(1):12-25.
Computer-Assisted Delivery of Cognitive-Behavioral Therapy for Addiction Has Enduring Effects
A unique feature of Cognitive Behavioral Therapy (CBT) for drug addiction developed by Dr. Kathleen Carroll and colleagues at Yale University is the fact that effects of treatment appear to endure long after treatment ends. Research has suggested that this may be a result of patients practicing and improving at implementing CBT skills over time. During a recent randomized clinical trial in an outpatient community treatment setting patients were randomly assigned to either standard treatment or standard treatment with biweekly access to computer-based training in CBT (CBT4CBT) skills. For those assigned to CBT4CBT the number of CBT modules initiated had a significant relationships to abstinence during follow-up (r=49, p=.02). Additionally results show that during the follow-up period CBT patients tended to demonstrate increases in abstinence while usual care patients increased drug use. Effects were evident up to the six month follow-up point. These data suggest that CBT4CBT is an effective adjunct to standard outpatient treatment for substance dependence. The computerized version appears similar to the in-person version in that it effects endure after therapy ends. This is significant because the disseminability of CBT via this platform holds potential for making this empirically validated treatment more broadly available than in-person treatment which requires skilled highly trained therapists for in person implementation. Carroll KM, Ball SA, Martino S, Nich C, Babuscio TA, Rounsaville BJ. Enduring effects of a computer-assisted training program for cognitive behavioral therapy: a 6-month follow-up of CBT4CBT. Drug Alcohol Depend. 2009; 100(1-2):178-81.
Group Contingency Management Is Feasible and Improves Attendance Rates
Dr. Kirby and colleagues at the Treatment Research Institute implemented a novel contingency management treatment program in which the behavior of a single, randomly selected, anonymous individual determined reinforcement delivery for the entire group. In traditional contingency management, rewards or sanctions are typically given following the behavior of an individual. This approach has shown to be efficacious for improving abstinence rates in drug treatment settings. However, this approach is not necessarily compatible with methadone treatment which tends to be conducted in a group treatment format. In this study contingencies placed only on cocaine abstinence (CA) were compared to contingencies on one of four behaviors (CA, treatment attendance, group CM attendance, and methadone compliance) selected randomly at each drawing. A goal of this research was to leverage the power of the group to assist group members who might initially struggle with achieving treatment goals. A second goal was to incorporate contingencies on behaviors other than abstinence which methadone counselors felt would be helpful for producing long term treatment success. Two groups of 22 cocaine-dependent community-based methadone patients were exposed to both CA and multiple behavior (MB) conditions in a reversal design counterbalanced across groups. The group CM intervention was feasible and appeared safe such that participants did not report experiencing coercion from other group members. Additionally, the MB condition improved group CM meeting attendance relative to the CA condition. This is significant because it demonstrates implementation of CM in a group format is possible in community treatment programs and shows that Multiple Behavior targeting approach has an advantage over a traditional abstinence based CM with respect to treatment attendance outcomes. Kirby KC, Kerwin ME, Carpenedo CM, Rosenwasser BJ, Gardner RS. Interdependent group contingency management for cocaine-dependent methadone maintenance patients. J Appl Behav Anal. 2008; 41(4):579-95.
Regular Exercise as a Protective Factor in Relapse following Smoking Cessation Treatment
Dr. Abrantes and colleagues at Butler Hospital and The Miriam Hospital conducted this study to determine if smokers who regularly exercised varied from those who did not on a number of baseline characteristics prior to initiating a smoking cessation intervention, as well as smoking cessation outcomes during the year after treatment. Baseline characteristics were examined for a sample of 524 smokers who participated in 12-week 2 x 2 clinical trial comparing standard smoking cessation treatment (ST) plus bupropion (BUP); ST plus placebo; ST plus cognitive behavioral therapy CBT for depression plus BUP; and ST plus CBT for depression plus placebo. Participants identified themselves as regular exercisers versus those who reported not exercising regularly. At baseline, exercisers were more likely to be female, have lower body mass index, report smoking fewer cigarettes per day, report lower smoking urges and have lower levels of depressive symptoms. At the end of treatment, abstinence rates were significantly higher for participants who took bupropion (42.7%) compared to placebo (27.1%), but these rates converged by the 12-month follow-up. Similarly, at the end of treatment, those who exercised regularly, independent of treatment condition, had significantly higher abstinence rates (40.1%) compared to non-exercisers (32.9%) but again abstinence rates converge at follow-up. Lastly, although rates of abstinence at the end of treatment were similar for exercisers (43.1%) and non-exercisers (42.4%) receiving bupropion, among smokers receiving placebo, abstinence rates were significantly higher for participants who exercised (36.9%) versus those who did not (24.1%). The authors suggest that regular exercise may be an important protective factor in smoking relapse and should continue to be explored as an adjunct to smoking cessation interventions. Abrantes AM, Strong, DR, Lloyd-Richardson, EE, Niaura, R, Kahler, CW, Brown, RA. Regular exercise as a protective factor in relapse following smoking cessation treatment. American Journal on Addictions. 2009;18(1):100-1.
Pain and Substance-Related Pain-Reduction Behaviors among Opioid Dependent Individuals Seeking Methadone Maintenance Treatment
Pain management in methadone maintenance treatment (MMT) represents an important clinical challenge. Prevalence estimates for chronic pain in MMT range from 37% with chronic severe pain to more than 60% with chronic pain of any intensity. Dr. Barry and colleagues from Yale University surveyed 293 opioid dependent individuals seeking MMT about their pain experiences and substance-related pain reduction behaviors. Among the 213 respondents reporting recent pain of at least moderate typical pain intensity, two-thirds had a lifetime history of chronic pain. In comparison to those without a lifetime history of chronic pain, those with a lifetime history were older, reported higher pain frequency, were more likely to endorse accident or surgery and less likely to endorse "don't know" as the genesis of their recent pain reduction behaviors. These findings may have implications for resources and program planning in MMT programs. Barry DT, Beitel M, Joshi D, Schottenfeld RS, Fiellin DA. Pain and substance-related pain-reduction behaviors among opioid dependent individuals seeking methadone maintenance treatment. Am J Addict. 2009;18(2):117-21.
Betting on Change: Modeling Transitional Probabilities to Guide Therapy Development for Opioid Dependence
What does change look like during treatment? Who is more likely to demonstrate it? And how can the process of change guide clinical decisions? The answers to these questions are relevant for understanding the effects of specific treatment procedures, identifying factors that can moderate specific intervening efforts, and developing therapy programs that are responsive to the ongoing process of change. Carpenter and others at Columbia University investigated the process of change by modeling transitions among four clinical states encountered in 64 detoxified opiate-dependent individuals treated with daily oral naltrexone: no opiate use, blocked opiate use (i.e., opiate use while adhering to oral naltrexone), unblocked opiate use (i.e., opiate use after having discontinued oral naltrexone), and treatment dropout. The effects of baseline characteristics and two psychosocial interventions of differing intensity, behavioral naltrexone therapy (BNT) and compliance enhancement (CE), on these transitions were studied. Participants using greater quantities of opiates were more likely than other participants to be retained in BNT relative to CE. Markov modeling indicated a transition from abstinence to treatment dropout was approximately 3.56 times greater among participants in CE relative to participants in BNT, indicating the more comprehensive psychosocial intervention kept participants engaged in treatment longer. Transitions to stopping treatment were more likely to occur after unblocked opiate use in both treatments. Continued opiate use while being blocked accounted for a relatively low proportion of transitions to abstinence and may have more deleterious effects later in a treatment episode. Carpenter KM, Jiang H, Sullivan MA, Bisaga A, Comer SD, Raby WN, Brooks AC, Nunes EV. Betting on change: modeling transitional probabilities to guide therapy development for opioid dependence. Psychol Addict Behav. 2009;23(1):47-55.
Cost Analysis of Clinic and Office-Based Treatment of Opioid Dependence: Results with Methadone and Buprenorphine in Clinically Stable Patients
The cost of providing and receiving treatment for opioid dependence can determine its adoption. Dr. Jones and others at Yale University School of Medicine sought to compare the cost of clinic-based methadone (MC, n=23), office-based methadone (MO, n=21), and office-based buprenorphine (BO, n=34) treatment and patient costs over 6 months of maintenance in patients who had previously been stabilized for at least 1 year. Results suggest the cost of providing 1 month of treatment per patient was $147 (MC), $220 (MO) and $336 (BO) (p<0.001). Mean monthly medication cost was $93 (MC), $86 (MO) and $257 (BO) (p<0.001). The cost to patients was $92 (MC), $63 (MO) and $38 (BO) (p=0.102). Sensitivity analyses, varying cost estimates and clinical contact, result in total monthly costs of $117 to $183 (MC), $149 to $279 (MO), $292 to $499 (BO). Monthly patient costs were $84 to $133 (MC), $55 to $105 (MO) and $34 to $65 (BO). The findings suggest that providing clinic-based methadone is least expensive, and the price of buprenorphine accounts for a major portion of the difference in costs. For patients, however, office-based treatment may be less expensive. Jones ES, Moore BA, Sindelar JL, O'Connor PG, Schottenfeld RS, Fiellin DA. Cost analysis of clinic and office-based treatment of opioid dependence: Results with methadone and buprenorphine in clinically stable patients. Drug Alcohol Depend. 2009;99(1-3):132-40.
Effects of Parent Skills Training with Behavioral Couples Therapy for Alcoholism on Children: A Randomized Clinical Pilot Trial
It has been widely documented that children living with an alcohol-abusing parent are more likely than their peers to exhibit behavioral problems that encompass both internalizing and externalizing symptoms. Although many factors contribute to these problems, inadequate parenting has been strongly linked to increased risks for children living with an alcohol-abusing parent. Drs. Lam, Fals-Stewart, and Kelley conducted this pilot study to examine preliminary effects of Parent Skills Training with Behavioral Couples Therapy on Children's behavioral functioning. Participants were men (N = 30) entering outpatient alcohol treatment, their female partners, and a custodial child between 8 and 12 years of age. Couples were randomly assigned to one of three equally intensive conditions: (1) Parent Skills with Behavioral Couples Therapy (PSBCT), (2) BCT (without parent training), or (3) Individual-Based Treatment (IBT; without couples-based or parent skills interventions). Parents completed measures of child externalizing and internalizing behaviors at pre-treatment, post-treatment, 6- and 12-month follow up; children completed self-reports of internalizing symptoms at each assessment. Only PSBCT participants reported significant effects on all child measures throughout the 12-month follow up. PSBCT showed medium to large effects in child functioning relative to IBT, and small to medium effects relative to BCT from baseline through follow up. Effect sizes suggest clinically meaningful differences between PSBCT and both BCT and IBT that warrant further empirical evaluation of BCT with parent training for alcohol-abusing men and their partners. Lam WK, Fals-Stewart, Kelly ML. Effects of parent skills training with behavioral couples therapy for alcoholism on children: a randomized clinical pilot trial. Addict Behav. 2008;33(8):1076-80.
Changing Network Support for Drinking: Network Support Project 2-Year Follow-Up
It has often been noted that the most significant problem related to treatment of alcohol dependence is not the attainment of initial abstinence but relapse following treatment. Given that an estimated one third of treated individuals relapse in the first 90 days after completion of treatment, Dr. Litt and colleagues at the University of Connecticut examined the role of changing network support in treatment. In this study, the Network Support Project was designed to determine whether a treatment could lead patients to change their social network from one that supports drinking to one that supports sobriety, with a focus on 2-years post-treatment. Alcohol-dependent men and women (N = 210) were randomly assigned to 1 of 3 outpatient treatment conditions: network support (NS), network support + contingency management (NS + CM), or case management (CaseM, a control condition). Analysis of drinking rates indicated that the NS condition yielded up to 20% more days abstinent than the other conditions at 2 years post-treatment. NS treatment also resulted in greater increases at 15 months in social network support for abstinence, as well as in Alcoholics Anonymous (AA) attendance and AA involvement than did the other conditions. Findings also suggested that social network changes were accompanied by increases in self-efficacy and coping that were strongly predictive of long-term drinking outcomes. These data indicate that a network support treatment can effect long-term adaptive changes in drinkers' social networks and that these changes contribute to improved drinking outcomes in the long term. Litt MD, Kadden RM, Kabela-Corimer E, Petry NM. Changing network support for drinking: network support project 2-year follow-up. J Consult Clin Psychol. 2009;77(2):229-42.
Coping Skills Training and Contingency Management Treatments for Marijuana Dependence: Exploring Mechanisms of Behavior Change
Achieving abstinence in the treatment of marijuana dependence has been difficult. To date the most successful treatments have included combinations of motivation enhancement treatment (MET) plus cognitive-behavioral coping skills training (CBT) and/or contingency management (ContM) approaches. Although these treatment approaches are theoretically based, their mechanisms of action have not been explored fully. Drs. Litt, Kadden, Kabela-Corimer, and Petry used a dismantling study design to investigate the mechanisms of behavior change from a marijuana treatment trial in which CBT and ContM were evaluated separately and in combination. Participants were 240 adult marijuana smokers, meeting criteria for cannabis dependence in an outpatient treatment research facility located in a university medical center. Participants were assigned to one of four 9-week treatment conditions: a case management control condition, MET/CBT coping skills training, ContM and MET/CBT + ContM. Outcome measures were total 90-day abstinence, recorded every 90 days for 12 months post-treatment. Regardless of treatment condition, abstinence in near-term follow-ups was predicted most clearly by abstinence during treatment, but long-term abstinence was predicted by use of coping skills and especially by post-treatment self-efficacy for abstinence. These findings suggest that the most efficacious treatments for marijuana dependence are likely to be those that increase self-efficacy. Litt MD, Kadden RM, Kabela-Corimer E, Petry NM. Coping skills training and contingency management treatment for marijuana dependence: exploring mechanisms of behavior change. Addiction. 2008;103(4):638-48.
Maintenance Treatment with Buprenorphine and Naltrexone for Heroin Dependence in Malaysia: A Randomized, Double-Blind, Placebo-Controlled Trial
Expansion of access to effective treatments for heroin dependence is a worldwide health priority that has the potential to reduce HIV transmission. Drs. Schottenfeld, Chawarski, and Mazlan compared the efficacy of naltrexone, buprenorphine, and no additional treatment in patients receiving detoxification and subsequent drug counseling for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviors. Specifically, 126 detoxified heroin-dependent patients, from an outpatient research clinic and detoxification program in Malaysia, were randomly assigned to 24 weeks of manual-guided drug counseling and maintenance with naltrexone (n=43), buprenorphine (n=44), or placebo (n=39). Primary outcomes, assessed by urine testing three times per week, were days to first heroin use, days to heroin relapse (three consecutive opioid-positive urine tests), maximum consecutive days of heroin abstinence, and reductions in HIV risk behaviors over 6 months. The study was terminated after 22 months of enrollment because buprenorphine was shown to have greater efficacy in an interim safety analysis. The findings highlight the importance of the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence. Schottenfeld RS, Chawarski MC, Mazlan M. Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomized, double-blind, placebo-controlled trial. Lancet. 2008;28;371(9631):2192-2200.
Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence
Despite the promising results of large clinical trials of high-dose naltrexone treatment for cocaine- and alcohol-dependent (CAD) patients, the gender disparity in response to high-dose naltrexone raises important clinical issues, including potential gender differences in naltrexone-associated adverse events and treatment non-adherence. In line with this central question, Dr. Suh and colleagues examined whether there are gender-specific differences in predictors of treatment attrition between CAD men and women who received a high-dose of naltrexone versus placebo, with one of two types of psychosocial therapies. Variables affecting differential outcome or attrition for men and women, including experience of nausea, substance use and severity of psychiatric problems were considered. Additionally, six variables to predict treatment attrition for men and women were: 1) randomized medication treatment condition (high-dose naltrexone or placebo); 2) randomized psychosocial treatment condition (cognitive behavioral therapy) or a medical management treatment model; 3) psychiatric severity prior to treatment, as women present with more severe psychiatric problems than men prior to substance use treatment, leading to treatment attrition; 4) experience of nausea, which is the most common adverse effect associated with the standard dose and high-dosage naltrexone, and a more frequently reported adverse event in women than men in naltrexone treatment; 5) alcohol use during treatment; and 6) cocaine use during treatment. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems or nausea while in treatment. These findings suggest the need for research delineating how outcomes may be affected by gender differences in pre-treatment characteristics as well as potential pharmacokinetic-differential effects of high-dose naltrexone. Suh JJ, Pettinati HM, Kampman KM, O'Brien CP. Gender differences in predictors of treatment attrition with high dose naltrexone in cocaine and alcohol dependence. Am J Addict. 2008;17(6):463-8.