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ABSTRACT: The clinical use of naltrexone (NTX) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes. In particular, the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear. The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes.
In an open-label naturalistic design, 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms: clonidine extended treatment (CET) (clonidine + psychosocial treatment), or enhanced extended treatment (EET) (oral NTX [1-10 mg/d] + CET) for 21 days. The primary outcome measure was retention in treatment. Secondary outcomes included abstinence from opioids, dropouts, and adherence to postdischarge care.
One hundred sixty-two patients (37.2%) accepted EET. Subjects receiving EET stayed longer in the program (F = 64.4; P = 0.000), were less likely to drop out, used less opioids, and followed through with referral to long-term outpatient treatment in a higher number, compared with patients in the CET arm (P = 0.000 in each case). The NTX + clonidine combination was safe and well tolerated.
This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients. Randomized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence.
Journal of Clinical Psychopharmacology 11/2007; 27(5):468-74. · 4.10 Impact Factor
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ABSTRACT: Incorporation of smoking cessation into cocaine treatment programs remains a challenge. A major concern is that cocaine abusers may tend to substitute one drug for the other. If this is true, successful treatment of cocaine abuse should lead to an increase in tobacco smoking. We compared tobacco smoking at admission, end of treatment and 9-month follow up for 168 crack cocaine dependent patients entering a 12-week outpatient treatment program for substance abuse. Smoking cessation was not a part of treatment. As expected cocaine patients improved with treatment and showed significant reduction in scores on the Addiction Severity Index (ASI). There were no significant changes in number of cigarettes smoked per day or scores on the Fagerstrom Test for Nicotine dependence (FTND) from baseline to end of treatment or follow-up. Also, there were no differences in the proportions of nonsmokers and smokers who changed their smoking habits over the treatment and follow up period. At follow up subjects who were abstinent as well as those using cocaine showed no changes in tobacco smoking. There is no evidence that reduction in crack cocaine smoking following treatment is accompanied by an increase in tobacco smoking. It appears that concerns over tobacco being substituted for cocaine may be unfounded in this population.
The American Journal of Drug and Alcohol Abuse 02/2006; 32(2):135-48. · 1.55 Impact Factor
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ABSTRACT: The serotonin transporter (5-HTT) regulates serotonin transmission and modulates behavioral effects of drug of abuse. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) yielding a short (S) and long (L) allele has been associated with severity of substance abuse. The aims of the study were to investigate whether 5-HTTLPR genotypes differed in their response to treatment in cocaine- and alcohol-abusing patients. Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism was performed in 141 African American cocaine-dependent patients with concurrent alcohol use who were entering a 12-week behaviorally oriented outpatient treatment program. In treatment, end of treatment and 6-month follow-up outcome measures included changes in Addiction Severity Index (ASI) scores, urine drug screens, days in treatment, individual/group sessions, dropout and completion rates. As expected, there was a reduction in substance abuse by the end of treatment and follow-up (F = 5.15, p = 0.000). However, there were no differences in the reduction in cocaine use across the LL, LS and SS genotypes. Interestingly, individuals with the S allele showed greater severity of alcohol use at admission (F = 4.84, p = 0.03), and the SS genotype showed less improvement in alcohol measures than the LL at follow-up (F = 3.68, p = 0.03), after controlling for baseline variables. While we found no association of the 5-HTTLPR variants with severity of cocaine abuse or any cocaine-related outcome measures, the data suggested that the 5-HTTLPR polymorphism may distinguish responders from non-responders to behavioral treatment in terms of alcohol use. Further investigations are required to determine the role of the 5-HTTLPR polymorphism in influencing treatment - outcome among substance abusers.
Addiction Biology 10/2005; 10(3):261-8. · 4.83 Impact Factor
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ABSTRACT: We investigated whether measures of impulsivity, aggression and sensation seeking differed between cocaine-dependent subjects and controls, and whether these measures were related to treatment-outcome for cocaine patients. Pre-treatment assessments of impulsivity (Barratt Impulsivity Scale [BIS]), aggression (Buss-Durkee Hostility Inventory [BDHI]) and sensation seeking (Zuckerman Sensation Seeking Scale [SSS]) were obtained for 141 African-American cocaine-dependent patients entering a 12-week, intensive outpatient treatment program and 60 controls. The outcome measures were number of negative urine drug screens, days in treatment, dropout rates and number of treatment sessions. Cocaine patients reported significantly higher scores on the SSS, the BIS and the BDHI than controls. Furthermore, the SSS scores showed a significantly negative correlation with days in treatment and negative urines, and a significant positive correlation with the dropout rate. The BIS and the BDHI scores were significantly associated with days in treatment and dropout rates respectively. A combination of the three variables contributed significantly toward predicting retention and abstinence. Higher levels of pretreatment impulsivity and aggression and sensation seeking seem to associated with poor treatment outcome for cocaine dependent patients receiving intensive outpatient treatment. Combining these behavioral measures with other clinical predictors may help in early identification of 'poor responders' who may benefit from additional or alternative treatment approaches.
Journal of Addictive Diseases 02/2004; 23(2):109-22. · 1.46 Impact Factor
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ABSTRACT: We investigated whether pretreatment measures of sensation seeking, impulsivity, and aggression were related to severity of cocaine use. Assessments of sensation seeking (SSS), impulsivity (BIS), and aggression (BDHI) were obtained for 140 African-American cocaine-dependent individuals entering outpatient treatment. We explored whether these variables were associated with addiction severity measures including quantity, frequency, and duration of cocaine use, scores on the Addiction Severity Index (ASI), and the admission urine drug screen status. A significant positive association was found between the total BDHI score and duration and frequency of cocaine use. Furthermore, SSS scores showed a significant positive correlation with frequency of cocaine use and cocaine positive admission urines. The BIS scores were significantly associated with 2 of the 7 ASI scales. Multiple regression analyses showed that the 3 measures contributed significantly toward predicting severity of cocaine use, but the contribution to the overall variance was modest. Measures of aggression and sensation seeking seem to be of clinical value in the assessment of cocaine abusers. However, these measures may need to be combined with other clinical and behavioral variables to accurately predict the severity of cocaine use.
Several lines of evidence support an association between traits of aggression, sensation seeking, and impulsivity, and substance abuse. First, high rates of substance abuse have been reported in clinical disorders such as bipolar disorders 1 and antisocial personality disorders 2 that are characterized by aggression and impulsivity. Lifetime prevalence rates of substance abuse have been reported to be over 90% among selected populations such as impulsive offenders. 3 Second, substance abusers have been found to exhibit significantly increased rates of impulse control disorders and violent behaviors compared with controls. 4-6 Third, studies employing psychometric assessments have found that cocaine abusers scored higher on measures of aggression and impulsivity compared with controls. 7,8 Fourth, childhood disorders associated with aggression and impulsivity such as conduct disorders and attention deficit disorders are consistently related to development of substance abuse in adolescence and adulthood. 9,10 It has been suggested that aggressive and impulsive individuals frequently experience negative emotional states such as irritability, anxiety, and dysphoria, and that substance use may be an attempt to alleviate the internal negative emotions. 11 Biologic studies also tend to support a link between aggression, impulsivity, and cocaine use. Cocaine has potent effects on cortical and subcortical dopamine systems that mediate initiation and control of behavior. 12 Chronic cocaine use has also been reported to impair serotonergic activity 13,14; serotonergic deficits have been linked to aggressive and impulsive behaviors. 15,16 These traits seem to be clinically important. Increased levels of aggression and impulsivity have been found to predict reduced retention and abstinence for cocaine abusers in treatment. 17,18 More disturbingly, self-destructive behavior, in particular violent suicide attempts, seem to be related to impulsive and aggressive traits among substance abusing patients. 16
Over the past decade, studies have examined several variables that may be associated with severity of drug use among cocaine abusers. Severity of cocaine use has been found to be related to demographic factors such as age and employment status, 19,20 anxiety and depressive symptoms, 20,21 polysubstance use, 22 antisocial personality, 23 and social stress. 24,25 Recent studies have also implicated biologic, possibly genetic factors, in determining severity of cocaine use. 26 Surprisingly, few studies have specifically studied the relationship between traits of aggression, sensation seeking, and impulsivity, and cocaine use, and the data is not consistent. In a study of 50 cocaine outpatients, Moeller et al 17 found that impulsivity was significantly correlated with severity of self-reported cocaine use and severity of cocaine withdrawal. Similarly, measures of aggression have been reported to be associated with substance abuse. 5 In contrast, Kasabrada et al 27 found no significant consistent relationship between sensation seeking and severity of cocaine use. Consistent with the literature, we had previously found that cocaine-dependent patients exhibit higher levels of aggression, sensation seeking, and impulsivity compared with controls. 28 The objective of this study was to examine whether measures of aggression, sensation seeking, and impulsivity are related to severity of cocaine use.
Addictive Disorders & Their Treatment 11/2003; 2(4):113-121.
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ABSTRACT: We studied whether pretreatment levels of learned helplessness (LH) were related to outcomes for substance-dependent individuals receiving high-structure, behaviorally oriented (HSB) or low-structure, facilitative (LSF) treatment. The subjects were 120 substance-dependent patients randomly assigned to the HSB or the LSF treatment style for up to 12 weeks of weekly individual counseling. The two groups were compared across pretreatment characteristics as well as in-treatment, end-of- treatment, and 9-month postadmission follow-up outcome measures. Outcomes reflected reduction in problem severity, abstinence, retention, dropout rate, and ratings of treatment benefit. Significant and comparable reductions in symptoms occurred for the HSB and LSF patients both during treatment and at follow-up. Comparisons of other outcomes also did not consistently favor either treatment style. However, significant and consistent interactions were observed between LH and treatment styles with respect to several outcome measures, and these effects were independent of pretreatment levels of depression, addiction severity, and readiness for treatment. Specifically, the more "helpless" patients did significantly better in HSB treatment, whereas the less "helpless" patients had better outcomes in LSF treatment. A matching approach that assigns patients to high- and low-structure treatments based on pretreatment levels of LH might improve treatment outcomes for substance-dependent patients.
The American Journal of Drug and Alcohol Abuse 09/2003; 29(3):567-84. · 1.55 Impact Factor
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ABSTRACT: Despite a close association between tobacco and cocaine use, few studies have systematically examined whether smoking predicts an adverse outcome for cocaine-dependent patients. We investigated whether severity of nicotine dependence was related to treatment outcome for cocaine-dependent individuals. Standardized assessments of nicotine dependence (Fagerström Test for Nicotine Dependence; FTND), cocaine use, and personality were obtained for 105 African American cocaine-dependent outpatients. Outcome measures included negative urine drug screens, days in treatment, dropout, and number of treatment sessions attended. The sample was stratified into cocaine-positive and cocaine-negative groups based on admission urine drug screens, and relationships between nicotine dependence and outcome measures were examined in each group. In the cocaine-negative group, higher FTND scores were negatively correlated with number of negative urine drug screens during treatment even after controlling for other predictors, whereas FTND scores were not correlated to outcome in the cocaine-positive group. It seems that severity of tobacco use predicts poor outcome for cocaine-dependent patients who are cocaine free at the time of admission into outpatient treatment.
Nicotine & Tobacco Research 07/2003; 5(3):411-8. · 2.58 Impact Factor
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ABSTRACT: Although seasonal fluctuations in several indices of serotonin function have been described, little is known about seasonality and serotonergic activity in substance abusers. We investigated whether there were seasonal differences in platelet serotonin transporter sites among cocaine dependent patients and controls. Platelet [(3)H]paroxetine binding, a measure of serotonin transporter sites, was assayed in 141 African-American cocaine-dependent subjects and in 60 race matched healthy volunteers who served as the control group. B(max) (density of serotonin transporter) and K(d) (affinity constant) values of [(3)H]paroxetine binding were compared during spring, summer, fall and winter. Consistent with our previous findings B(max) values were significantly lower in cocaine patients (639 +/- 234) than in controls (906 +/- 225) (t = 7.12, p < 0.001). Moreover, B(max) values showed a significant seasonal variation in controls with the highest values in summer and spring compared with fall and winter (F = 4.47, p < 0.01). However, there were no significant seasonal differences in B(max) values in cocaine patients. K(d) values did not show any seasonal changes in either group. There were no effects of age or gender on seasonal variations in B(max). The study demonstrates a seasonal effect on platelet serotonin uptake in healthy African-American volunteers. The lack of seasonal differences in transporter availability in cocaine patients indicates that the normal seasonal rhythm of serotonergic activity may be disturbed in cocaine abusers. Biological studies that employ platelet serotonin transporter sites as a marker of serotonin function should consider seasonal variations in these markers as a potential source of variance.
Human Psychopharmacology Clinical and Experimental 03/2003; 18(2):103-11. · 2.48 Impact Factor
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ABSTRACT: Despite substantial preclinical evidence that supports the involvement of noradrenergic (NA) and serotonergic (5-HT) mechanisms in alcohol withdrawal, human data remain inconsistent. We examined whether plasma levels of NA and 5-HT were altered during alcohol withdrawal and whether these measures were related to craving. We also explored whether alterations in NA and 5-HT activity differ between type I and type II alcohol-dependent patients during withdrawal.
Plasma measurements of NA and 5-HT and assessments of craving were performed longitudinally in 26 Caucasian alcohol-dependent men who were hospitalized for detoxification, at baseline (day 0), and on the 1st, 7th and 14th days of withdrawal. These measures were compared with NA and 5-HT levels obtained in 28 controls.
During withdrawal, NA levels declined significantly from day 1 through day 14, whereas 5-HT levels and craving declined significantly from day 0 through day 14. The NA levels on days 0 and 1 of withdrawal were significantly higher than those in controls; however, by day 7 the NA levels were similar to the control values. In contrast, the 5-HT levels on day 0 of withdrawal resembled control values; however, the 5-HT concentrations on days 1, 7 and 14 were significantly lower than those in controls. There were no significant correlations between NA and 5-HT levels or between craving and the biological measures during withdrawal. Type I and type II patients did not differ in NA or 5-HT levels during withdrawal.
These findings indicate that both plasma NA and 5-HT levels change during withdrawal; however, the pattern of change is different for the two measures. Also, while alterations in NA activity appear to normalize by late withdrawal, 5-HT changes seem to be more persistent. Neither craving nor subtypes of alcoholism seem to be related to alterations in NA or 5-HT during withdrawal.
Alcohol and Alcoholism 38(3):224-31. · 2.95 Impact Factor
