[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy].

OBJECTIVE: To evaluate efficacy and safety of injectable extended-release naltrexone (XR-NTX, Vivitrol), an opioid receptor antagonist, in the treatment of opioid dependence, we carried out a 1-year open-label extension study. MATERIAL AND METHODS: The study followed the initial 6-month randomized, double-blind, PBO-controlled investigation of XR-NTX, used in dose 380 mg, as a treatment for opioid dependence. The study was conducted at 13 clinical sites in Russia. The main measurements were monthly urine samples (efficacy) and adverse events (safety). RESULTS AND CONCLUSION: The open-label extension included 114 patients (67 continued on XR-NTX and 47 switched from placebo). Overall, 62.3% (95% CI: 52.7%, 71.2%) of patients completed the extension. Urine testing revealed that 50.9% (41.5%, 60.4%) were abstinent from opioids at all assessments during the 1-year open-label phase. Adverse events were reported by 21.1% of patients. Elevations in liver function tests occurred in 16.7% of patients. No severe adverse events were reported. The data obtained demonstrate the long-term safety and efficacy of XR-NTX in opioid dependent patients.

[Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomized trial].

UNLABELLED: We aimed to assess the efficacy and safety of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. Two hundreds and fifty patients with opioid dependence were enrolled into the double-blind, placebo-controlled, randomized, 24-week trial. Patients aged 18 years or over who had inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX (n=124) or placebo (n=126). Participants also received 12 biweekly counseling sessions. The primary endpoint was the response profile for confirmed abstinence during weeks 5-24 assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid- free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. IN CONCLUSION: XR-NTX represents a new treatment option. XR-NTX in conjunction with psychosocial treatment was more effective for treatment of opioid dependence compare to psychosocial support and placebo.

Impact of psychosocial treatments on associated problems of cocaine-dependent patients.

A previous report from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (P. Crits-Christoph et al., 1999) found relatively superior cocaine and drug use outcomes for individual drug counseling plus group drug counseling compared with other treatments. Using data from that study, the authors examined the relative efficacy of 4 treatments for cocaine dependence on psychosocial and other addiction-associated problems. The 487 patients were randomly assigned to 6 months of treatment with cognitive therapy, supportive-expressive therapy, or individual drug counseling (each with additional group drug counseling), or to group drug counseling alone. Assessments were made at baseline and monthly for 6 months during the acute treatment phase, with follow-up visits at 9 and 12 months. No significant differences between treatments were found on measures of psychiatric symptoms, employment, medical, legal, family-social, interpersonal, or alcohol use problems. The authors concluded that the superiority of individual drug counseling in modifying cocaine use does not extend broadly to other addiction-associated problems.

Patient placement criteria and their relation to access to appropriate level of care and engagement in alcoholism treatment.

Patient placement criteria (PPC) facilitate treatment matching through detailed, standardized assessment of patients' needs. This process affords the alcoholism treatment field an opportunity to address issues that influence access to appropriate level of care by highlighting these issues during the assessment. The American Society of Addiction Medicine Patient Placement Criteria can integrate assessment of social and environmental, institutional and patient issues that affect access to appropriate care and treatment engagement. They can ultimately improve access through an iterative approach: developing a broad consensus on guidelines based on research evidence and expert clinical opinion, making criteria clear and easy to use both for assessment and for teaching purposes, addressing the needs of special populations, and testing and improving the validity of decision rules to achieve optimal access and treatment engagement. Early evidence suggests that PPC are promising but there is much about them that remains to be tested and improved.

Gender differences in cocaine craving among non-treatment-seeking individuals with cocaine dependence.

The purpose of this pilot study was to evaluate potential gender differences in cocaine craving among non-treatment seekers with cocaine dependence. We examined 10 female and 11 male individuals matched by demographic characteristics and severity of drug use; we used a multidimensional questionnaire that assesses various aspects of craving: (a) current intensity, (b) projected intensity, (c) resistance to use cocaine, (d) responsiveness to drug-related conditioned stimuli, and (e) imagined likelihood of use if in a setting with access to drugs. Other instruments utilized were the Hamilton Rating Scale for Depression and Addiction Severity Index. Female subjects had higher total craving scores (p < .05), with post hoc tests showing more present desire to use cocaine and responsivity to drug-conditioned stimuli, along with lower scores on the desire not to use cocaine. In exploratory analyses, we found greater depressive symptomatology (p = .02) and severity of family/social problems (p = .02) in females than their males counterparts. These results suggest that gender may influence different aspects of cocaine craving. As estrogen is purported to modulate craving-related dopaminergic systems, further studies will be needed to confirm these observed gender differences and to investigate their possible mechanisms, particularly estrogen-dopamine interactions and their effect on craving and mood.

Clinical outcomes following cocaine infusion in nontreatment-seeking individuals with cocaine dependence.

BACKGROUND: In this study we explored if laboratory-based cocaine administration to human subjects was associated with long-term adverse outcomes. METHODS: Twenty-one non--reatment seeking individuals with cocaine dependence were evaluated at baseline and again 5 and 10 months following cocaine infusion in a brain imaging study. Outcomes included computer-driven multidimensional clinical assessments and radioimmunoassay of hair. For comparison, identical data were collected from 19 cocaine-dependent subjects who did not receive the infusion. RESULTS: The infused and noninfused groups did not differ on frequency of cocaine use (corroborated by radioimmunoassay of hair), Addiction Severity Index drug composite score, or Hamilton Rating Scale for Depression score at both follow-up time points. In a time-related trend analysis, both groups showed significant reductions in frequency of cocaine use. CONCLUSIONS: Laboratory-based cocaine administration can be a safe paradigm even in individuals who are not engaged in treatment.

Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hormones and clinical outcomes.

This study explored the acute and long-term consequences of ultrarapid opioid detoxification (URD) in individuals with opioid dependence. In an open case series, seven patients underwent URD and subsequent treatment with daily naltrexone. Structured interviews, integrated rehabilitation and hair sampling were employed in the 12-week course of longitudinal follow-up. Cardiac and pulmonary physiology did not change significantly during the anesthesia phase of URD, but plasma ACTH and cortisol levels increased 15- and 13-fold, respectively. Marked withdrawal and tachypnea in all patients and respiratory distress in one patient occurred during the acute post-anesthesia phase. Withdrawal scores were significantly elevated for 3 weeks compared with baseline in the face of minimal self-reported craving for opioids. Anxiety, depression and vegetative symptoms improved gradually. Four patients remained abstinent of opioid use, two reported a brief period of opioid intake and one relapsed into daily opioid consumption. Given its effect on breathing and stress hormones, this procedure should be conducted by experienced anesthesiologists. The fact that URD and subsequent naltrexone treatment appears to cause a dissociation effect in the usual relationship between withdrawal and craving has implications for behavioral pharmacology. Further research is needed on the efficacy, safety, mechanisms and neurobiological sequelae of the procedure.

Predictors of self-help group attendance in cocaine dependent patients.

OBJECTIVE: While referral to self-help groups for patients dependent on drugs other than alcohol has become widespread in the substance abuse treatment field, little is known about the characteristics of people who attend these groups. This study examines particular sociodemographic and clinical characteristics as possible predictors of attendance at self-help groups in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study. METHOD: A multicenter study randomly assigned 487 patients (76.8% men) to one of four psychosocial treatments for cocaine dependence. Patients were treated for 24 weeks. Among other measures, the Weekly Self-Help Questionnaire was administered each week and completed, at least once, by 411 subjects. RESULTS: Approximately two thirds of the patients attended one or more self-help meetings during the 24-week period. Patients initially more likely to attend self-help groups frequently were those who were unemployed, had no religious preference, had more severe baseline drug use and reported treatment for prior substance-related problems. Patients with more severe baseline drug use and those who previously received treatment for substance-related problems were more likely to maintain frequent attendance throughout the study period. Only severity of baseline drug use predicted more frequent attendance during Month 6, although there was a trend in Month 6 favoring more frequent attendance by women. These findings remained significant when treatment condition was added to the models. CONCLUSIONS: Although these findings are consistent with past research on alcohol dependent individuals, they challenge popular clinical notions about the types of people who attend self-help groups. These findings demonstrate that self-help groups can appeal to a wide variety of cocaine dependent patients.

The validity of self-reported drug use in non-treatment seeking individuals with cocaine dependence: correlation with biochemical assays.

Accurate estimate of drug exposure plays an important role in studies of the neurobiology of drug dependence. The validity of self-reported drug use by subjects participating in such studies has not been well established. This study examined the relationship between self-reported drug use and biological markers in 18 non-treatment-seeking cocaine-dependent individuals participating in research on the effects of cocaine on the brain. A significant relationship was found between self-reported frequency of cocaine use and hair cocaine concentration. Frequency of alcohol use correlated significantly with plasma carbohydrate-deficient transferrin and aspartate aminotransferase levels. These results suggest that self-reported substance use in non-treatment seeking research subjects is generally valid.

Self-help group attendance and participation among cocaine dependent patients.

The authors examined frequency and patterns of self-help group attendance and active participation over a 6-month period among 411 patients receiving treatment in the NIDA Collaborative Cocaine Treatment Study. Nearly two-thirds of patients attended at least one self-help group, and nearly all of these actively participated. Alcoholics Anonymous and Narcotics Anonymous meetings were attended most frequently. Statistical analyses included chi square, one-way analyses of variance, and cluster techniques. While patterns of attendance were relatively consistent over time, findings suggest that a treatment emphasizing the importance of self-help groups is likely to encourage more self-help group attendance and participation over time.

Comorbidity, smoking behavior and treatment outcome.

BACKGROUND: A sizeable sector of the population continues to smoke cigarettes despite our efforts to prevent and treat this addiction. We explored the relationships between lifetime comorbidity, psychiatric symptomatology, smoking behavior and treatment outcome to better understand vulnerability to smoking and treatment response. METHODS: One hundred and twenty smokers at two sites were enrolled in a multicenter, double-blind, randomized, 10-week smoking cessation trial with fluoxetine and behavioral treatment. The Structured Clinical Interview for DSM-III-R and Hamilton Depression Rating Scale were administered prior to treatment initiation. Self-report measures were used to assess psychiatric symptoms throughout treatment and during a 6-month follow-up period. RESULTS: Overall 62.3% of our sample were diagnosed with a lifetime mood, anxiety or substance use disorder despite stringent study exclusion criteria. Lifetime comorbidity was shown to be related to higher smoking rates and nicotine dependence, depressed mood and greater self-report of anxiety and stress. Lifetime comorbidity, however, alone or in combination with treatment condition, failed to predict treatment outcome (at posttreatment or follow-up). Baseline depression scores (Beck Depression Inventory, BDI) were related to treatment outcome only for smokers without a positive history of any psychiatric disorder or depression, with lower BDI scores more frequent in those who were abstinent. CONCLUSIONS: High prevalence rates of lifetime psychiatric illness and substance use disorders are reported for chronic smokers. Subsyndromal psychiatric symptoms may play a role in smoking behavior in combination with diagnosable disorders. Clinicians need to carefully assess both psychiatric diagnoses and symptoms in chronic smokers to optimize patient-treatment matching.

The Addiction Severity Index: a field study of internal consistency and validity.

This study investigated whether the use of the Addiction Severity Index (ASI) in a network of inner-city alcohol and drug abuse clinics under nonideal conditions would yield internally consistent and valid data. A sample of 8,984 ASI scores was collected over a 34-month period. Construct validity was examined by computing the internal consistency of all subscales. Convergent and divergent validity of composite scores and of severity ratings were evaluated using correlation matrices. Findings demonstrated that ASI scores were internally consistent and valid, even though the recommended administration protocol may not always have been followed as faithfully as might be desirable. This robustness bodes well for the use of the ASI in on-line clinical environments. Results should be viewed with caution until the reliability of ASI administration is tested under similar nonideal conditions and until permissible deviations from standard protocol can be quantified.

Placement matching: challenges and technical progress.

Although it is highly desirable, standardized placement matching for substance use disorders poses challenges due to variability in settings, services, and syndromes; multidimensionality of clinical problems; multiplicity of outcome constructs; and temporal phenomena in the course of recovery. Despite these obstacles, progress is being made in developing patient placement criteria that are comprehensive with adequate reliability, feasibility, and resolution. With these methodological advances, it has been possible to initiate controlled research with placement criteria. The first such studies provide early evidence supporting such criteria and indicate areas for refinement.

Depressive symptomatology and cocaine-induced pituitary-adrenal axis activation in individuals with cocaine dependence.

The hypothalamic-pituitary-adrenal (HPA) axis plays a role in cocaine dependence and major depressive disorder. The authors examined the correlation between baseline depressive symptomatology and pituitary-adrenal axis activation induced by acute cocaine challenge. Twelve patients with cocaine dependence were administered an iv bolus of cocaine (0.6 mg/kg) and their plasma was assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. Depressive symptomatology was assessed with total Hamilton rating scale for depression (HRSD) scores and its vegetative and cognitive superfactors. Cocaine produced a mean increase from baseline of 261% for ACTH and 73% for cortisol plasma levels. Changes in ACTH (r=0.69) and cortisol (r=0.59) were positively and significantly correlated with total HRSD scores and its vegetative, but not cognitive, factor symptom cluster. These results suggest that the HPA axis may be involved in affective disturbances associated with the use of cocaine. Implications of these data for the pathophysiology of cocaine dependence are discussed.

Feasibility of multidimensional substance abuse treatment matching: automating the ASAM Patient Placement Criteria. American Society of Addiction Medicine.

UNLABELLED: The Patient Placement Criteria published by the American Society of Addiction Medicine (ASAM Criteria) established a non-proprietary standard for matching substance use disorder patients to treatment settings. METHODS: Data from 593 substance dependent adults who were assessed using the first computerized implementation of the ASAM Criteria were analyzed to determine whether the level of care assignments showed significant differences on a variety of clinical measures. RESULTS: The algorithm showed acceptable discrimination between each of three ASAM Levels of Care across numerous clinical subscales. CONCLUSIONS: It is feasible to implement complex, multidimensional criteria for substance abuse treatment that may improve reliability and facilitate validity studies.

Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study.

BACKGROUND: This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients. METHODS: Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month. RESULTS: Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed. CONCLUSION: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.

Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects.

The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.

The Addiction Severity Index as a screen for trauma and posttraumatic stress disorder.

OBJECTIVE: The Addiction Severity Index (ASI) includes items to assess patients' history of trauma (physical or sexual). The goal of this study was to assess the sensitivity and specificity of those questions in relation to the Trauma History Questionnaire (THQ), a more thorough measure of lifetime trauma and, in addition, to an actual posttraumatic stress disorder (PTSD) diagnosis. METHOD: At the start of treatment cocaine dependent outpatients (N = 110, 65.5% male) were assessed on the ASI, the THQ and a PTSD symptom checklist as part of a multisite clinical trial. RESULTS: Specificity of the ASI questions was higher than sensitivity for both sexual trauma (specificity = .96, sensitivity = .46) and physical trauma (specificity = .71, sensitivity = .50), while for PTSD the sensitivity of the ASI (.91) was higher than its specificity (.43). Other findings indicated that patients were more likely to report trauma on the THQ than on the ASI (which may be due to the self-report format of the THQ); that the ASI was better at assessing sexual than assessing physical trauma; and that the higher the number of ASI trauma items endorsed, the more likely was the PTSD diagnosis. Finally, PTSD patients had greater severity than non-PTSD patients on other ASI items (e.g., psychological severity, need for treatment). CONCLUSIONS: The ASI trauma questions show stronger utility as a screen for PTSD than for trauma. Results of the study are discussed in light of ways to modify the ASI to screen more accurately for trauma, clinical implications, and limitations of the study method.