Outcome predictors in cocaine dependence treatment trials

Finding the predictors of outcome in outpatient cocaine dependence treatment trials may be useful for the development of both psychosocial as well as pharmacological treatments for cocaine dependence. Among the most powerful predictors of response to psychosocial treatment are cocaine withdrawal symptom severity and the results of a urine drug screen (UDS) collected at study entry. The present trial seeks to extend these findings by examining outcome predictors in a large number of subjects participating in a series of outpatient cocaine pharmacotherapy trials while selecting three separate criteria to define successful outcome. The ability of several baseline variables were tested to predict treatment outcome in a series of cocaine medication trials that included 402 cocaine-dependent subjects. Predictor variables included results from the baseline Addiction Severity Index (ASI), initial UDS results, and cocaine withdrawal symptom severity at treatment entry, as measured by scores on the Cocaine Selective Severity Assessment (CSSA). Outcome measures included UDS results obtained during the trials and results from the ASI gathered at the end of the trials. Baseline variables that most consistently predicted treatment outcome were the initial UDS results and initial CSSA scores. These findings indicate that baseline UDS results and CSSA scores are powerful predictors of outcome and should be used as stratifying variables in outpatient cocaine medication trials.     

Cocaine withdrawal symptoms identify "Type B" cocaine-dependent patients

Recent studies of substance dependence typologies briefly show that multivariate systems originally developed for identifying subtypes of alcoholics, such as Babor's Type A and B system, may also be valid in abusers of other substances, such as cocaine. Type B patients are characterized by an earlier onset of addiction and more severe symptoms of their addiction, psychopathology, and impulsivity. The Type B classification has also been associated with deficits in serotonergic function. We have found that patients who exhibit more severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), have poor treatment outcome and share many characteristics with "Type B" patients. In this paper, we review baseline characteristics of cocaine-dependent patients from several recently completed outpatient cocaine dependence treatment trials to assess the association of cocaine withdrawal symptom severity and the Type B profile. Identifying subtypes of cocaine-dependent patients may improve our ability to treat cocaine dependence by targeting treatments for specific subtypes of patients. We examined the ability of the CSSA scores to capture Type B characteristics in cocaine dependence by analyzing a series of cocaine medication trials that included 255 cocaine-dependent subjects. High CSSA scores at baseline were associated with a history of violent behavior, a family history of substance abuse, antisocial personality disorder, higher addiction severity, and co-morbid psychiatric diseases. Patients with high CSSA scores are also more likely to meet criteria for Type B (Type II) cocaine dependence. Identifying Type B cocaine-dependent patients may help to develop targeted psychosocial or pharmacological treatments for these difficult-to-treat patients.     

Alcohol use affects the outcome of treatment for cocaine abuse

This study investigated whether alcohol use affects baseline characteristics and treatment outcome in 128 adults who participated in a randomized trial of cognitive behavioral vs. 12-step treatment for crack cocaine abuse. Assessments were taken at baseline and weeks 4, 8, 12, and 26 on biologically-verified cocaine abstinence and psychometric measures. Alcohol use was measured at intake and subsequent assessments using the Addiction Severity Index (ASI) and self-reported frequency of alcohol consumption. Results indicate alcohol use at baseline was associated with increased baseline cocaine use and ASI drug severity but was not associated with ASI psychiatric severity, psychiatric diagnoses, or other baseline variables. Alcohol use at baseline did not predict worse treatment outcome for cocaine abstinence. However, alcohol use after four weeks of treatment did predict ability to achieve cocaine abstinence at assessment points during and after treatment.     

Prediction of Treatment Outcome by Baseline Urine Cocaine Results and Self‐Reported Cocaine Use for Cocaine and Opioid Dependence

This study examined the usefulness of baseline cocaine urine toxicology results and self‐reported days of cocaine use in predicting treatment response in cocaine‐ and opioid‐dependent subjects. Ninety‐nine male and 52 female subjects, maintained on buprenorphine, participated in a 24‐week, randomized, double‐blind, four‐cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had cocaine‐positive and 49 (32%) cocaine‐negative urines at the beginning of treatment. For the previous 30 days before study participation, 91 (60%) subjects reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%) subjects reported more than 15 days (high baseline cocaine use). By using the treatment effectiveness score (TES) as the outcome measure, a negative urine for cocaine at baseline predicted a better outcome during a 24‐week trial for cocaine and opioid use. There also was a significant interaction between baseline cocaine urine results and desipramine response with the urine cocaine‐negative group showing greater desipramine response than placebo for opioid and cocaine use. Self‐reported cocaine use at baseline did not show significant predictive power for TES scores during the clinical trial. These results suggest that baseline cocaine urine results should be considered as stratifying variables in clinical trials for cocaine dependence.     

Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes

Aim To examine whether withdrawal after abstinence and cue‐elicited craving were associated with polymorphisms within two genes involved in regulating the endocannabinoid system, cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH). Two single nucleotide polymorphisms (SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers. Participants Participants were 105 students at the University of Colorado, Boulder between the ages of 18 and 25 years who reported smoking marijuana daily. Measurements Participants were assessed once at baseline and again after 5 days of abstinence, during which they were exposed to a cue‐elicited craving paradigm. Outcome measures were withdrawal and craving collected using self‐reported questionnaires. In addition, urine samples were collected at baseline and on day 5 for the purposes of 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THC–COOH) metabolite analysis. Findings Between the two sessions, THC–COOH metabolite levels decreased significantly, while measures of withdrawal and craving increased significantly. The CNR1 SNP displayed a significant abstinence × genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence × genotype interaction on craving. Conclusions These genetic findings may have both etiological and treatment implications. However, longitudinal studies will be needed to clarify whether these genetic variations influence the trajectory of marijuana use/dependence. The identification of underlying genetic differences in phenotypes such as craving and withdrawal may aid genetically targeted approaches to the treatment of cannabis dependence.     

Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial

Aims Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double‐blind, placebo‐controlled out‐patient trial tested topiramate for treating methamphetamine addiction. Design Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 50 mg/day to the target maintenance of 200 mg/day in weeks 6–12 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. Setting The trial was conducted at eight medical centers in the United States. Participants One hundred and forty methamphetamine‐dependent adults took part in the trial. Measurements The primary outcome was abstinence from methamphetamine during weeks 6–12. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables. Findings In the intent‐to‐treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 6–12. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer‐rated severity of dependence scores significantly. Subjects with negative urine before randomization (n = 26) had significantly greater abstinence on topiramate versus placebo during study weeks 6–12. Topiramate was safe and well tolerated. Conclusions Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent.     

Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol

This study compared the effects of alcohol and cocaine dependence severity on the outcome of outpatient detoxification from alcohol and cocaine. Subjects included 84 subjects with both alcohol and cocaine dependence admitted for outpatient detoxification. Fifty-three of the 84 subjects (63%) completed detoxification. Baseline cocaine use, cocaine craving, and cocaine withdrawal symptoms predicted detoxification outcome, whereas alcohol use, alcohol craving, and alcohol withdrawal symptoms did not. Among cocaine- and alcohol-dependent subjects, cocaine dependence severity appears to be a more important predictor of detoxification success than alcohol dependence severity.     

Effectiveness of Motivational Incentives in Stimulant Abusing Outpatients with Different Treatment Histories

Objective: To determine if prize-based abstinence incentives will differentially affect substance abuse outcomes in patients with different treatment histories. Design: Treatment seeking outpatients with more or less prior treatment episodes were randomized to receive either prize-based incentives plus treatment as usual (TAU) or TAU alone. Outcome variables included longest sustained period of abstinence, number of negative urine drug screens (UDS), and retention in treatment. Results: Treatment experienced participants were older, more likely to be female, African American, unemployed, and with more severe cocaine and psychiatric problems. The effectiveness of incentives did not differ significantly between the two treatment history groups with regard to the outcome measures.     

Can Cocaine Craving Be a Medication Development Outcome?

Craving, which ranges from a sustained desire for drugs persisting for weeks to an acute desire passing within minutes, has been described as an important clinical precipitant of relapse in cocaine and opioid abusers and may be a useful surrogate outcome for developing new drug abuse pharmacotherapies. Whereas craving for opioids frequently has been conceptualized as the negative reinforcer of protracted withdrawal or “drug hunger,” craving for cocaine has been conceptualized as the positive reinforcer of remembered euphoria. Medications can reduce both sustained cocaine craving and acute craving induced by a single dose of cocaine, and reductions in both types of craving are correlated with reductions in cocaine use. Furthermore, high levels of craving during treatment or during cue-induced challenges predict poor treatment response and later relapse to cocaine abuse in those who have attained abstinence.     

Effectiveness of motivational incentives in stimulant abusing outpatients with different treatment histories

OBJECTIVE: To determine if prize-based abstinence incentives will differentially affect substance abuse outcomes in patients with different treatment histories. DESIGN: Treatment seeking outpatients with more or less prior treatment episodes were randomized to receive either prize-based incentives plus treatment as usual (TAU) or TAU alone. Outcome variables included longest sustained period of abstinence, number of negative urine drug screens (UDS), and retention in treatment. RESULTS: Treatment experienced participants were older, more likely to be female, African American, unemployed, and with more severe cocaine and psychiatric problems. The effectiveness of incentives did not differ significantly between the two treatment history groups with regard to the outcome measures.     

Pre-treatment characteristics, program philosophy and level of ancillary services as predictors of methadone maintenance treatment outcome

Predictors of methadone maintenance treatment outcome have not been extensively studied as they relate to variations in program philosophy, nor have such predictors received much examination among recently treated, older cohorts of opioid addicts for whom drug use patterns have changed. Predictors of outcome were examined at 18 months post-treatment entry for 353 admissions to methadone maintenance who received random assignment to one of three counseling conditions: (1) medication only, (2) standard counseling and (3) enhanced services; and one of two contingency conditions: (1) no contingencies, and (2) contingency contracting in a six-cell 3x2 design. Subjects in contingency contracting conditions were placed on contingency contracts for positive urine toxicology results and ultimately discharged for unremitting drug use. All subjects completed the Addiction Severity Index (ASI) and provided weekly urine specimens. Predictors of urinalysis results and treatment retention were determined using bivariate and multivariate techniques. Interactions between subject characteristics by experimental condition assignment were also examined as predictors. Higher rates of total positive urine specimens were predicted by younger age, greater pre-treatment frequency of smoking cocaine, lower ASI psychiatric composite scores, and higher ASI legal composite scores. Higher rates of opiate positive specimens were predicted by younger age, lower pre-treatment frequency of alcohol intoxication, higher ASI legal and lower ASI employment and psychiatric composite scores, and assignment to medication only/no contingencies condition. Higher rates of cocaine positives were predicted by younger age, black race, lower ASI psychiatric composite score, greater pre-treatment frequency of intravenous and smoked cocaine use, less pre-treatment frequency of marijuana use, and lower methadone dose level. Assignment to enhanced/contingency contracting predicted lower rates of cocaine positives. Treatment retention was predicted by older age, non-black race, lower ASI legal composite score, higher methadone dose level and assignment to non-contingent conditions. While subject variables over which treatment providers have little control were, thus, related to outcome, type of treatment provided and methadone dose also influenced outcome.     

Treatment outcome predictors for cocaine dependence

Over the past decade, a large number of potential medications have been examined in clinical trials for cocaine dependence. Unfortunately, no effective pharmacotherapies for cocaine dependence have been found to date. Although effective treatments for cocaine dependence are still being investigated, a few variables have been found to significantly predict cocaine treatment response. These variables include cocaine use variables, such as days of cocaine use in the month before treatment, baseline urine cocaine results, and cocaine withdrawal symptoms. Comorbid depression and alcohol use have also been shown to be risk factors for relapse. Among personality variables, impulsivity and similar personality traits may predict treatment response. Initial promising findings with genetic polymorphism, brain activation, and stress response have also been found and need to be replicated in future studies.     

Treatment Outcome Predictors for Cocaine Dependence

Over the past decade, a large number of potential medications have been examined in clinical trials for cocaine dependence. Unfortunately, no effective pharmacotherapies for cocaine dependence have been found to date. Although effective treatments for cocaine dependence are still being investigated, a few variables have been found to significantly predict cocaine treatment response. These variables include cocaine use variables, such as days of cocaine use in the month before treatment, baseline urine cocaine results, and cocaine withdrawal symptoms. Comorbid depression and alcohol use have also been shown to be risk factors for relapse. Among personality variables, impulsivity and similar personality traits may predict treatment response. Initial promising findings with genetic polymorphism, brain activation, and stress response have also been found and need to be replicated in future studies.     

Short-term outcomes after brief ambulatory opioid detoxification with buprenorphine in young heroin users

Aims This study examines the outcomes at 1, 3 and 6 months after a very brief outpatient detoxification with buprenorphine in 18–25‐year‐old heroin users. Design Prospective follow‐up study. Setting Outpatient drug treatment clinic, providing brief detoxification in downtown Baltimore, Maryland, USA. Participants One hundred and twenty‐three subjects between 18 and 25 years old; 56% male; 95% Caucasian; seeking detoxification; living in Baltimore City and five surrounding counties. Intervention Detoxification with buprenorphine over 3 days. Follow‐up at 1, 3 and 6 months. Measurements Drug use history, the Addiction Severity Index at baseline and follow‐up, urine drug screens, evaluation of the detoxification experience. Findings By self‐report, 37% of the total sample were not currently using heroin at 1 month, 32% at 3 months and 29% at 6 months, and 6.7%, 10.1% and 11.8% had an opioid negative urine test at 1, 3 and 6 months, respectively. There was a significant reduction from the baseline in mean Addiction Severity Index drug use composite score, as well as the mean number of days of heroin and cocaine use during past 30 days, that was sustained over the three follow‐up points. Engagement in aftercare was generally poor. Conclusions The findings show a reduced frequency and intensity of drug use, suggesting a possible role for brief outpatient detoxification in reducing the severity of dependence for some younger heroin users who may not yet be ready to engage in long‐term abstinence‐oriented or opioid substitution treatments.     

Olanzapine in Cocaine Dependence: A Double‐Blind,Placebo‐Controlled Trial

Preclinical and uncontrolled human studies have suggested the possible efficacy of second‐generation antipsychotics, particularly olanzapine, in treating cocaine dependence. We conducted a randomized, double‐blind, placebo‐controlled trial in which 48 cocaine‐dependent subjects received olanzapine or identical‐appearing placebo for 16 weeks. The primary outcome measure was the proportion of cocaine‐negative weekly urine screens during treatment. Secondary measures included scores on a Craving Questionnaire, Addiction Severity Index subscales, and extrapyramidal symptom scales. Olanzapine and placebo did not differ on any outcome measure. Both olanzapine and placebo subjects frequently reported side effects, but no unexpected ones. We conclude that olanzapine appears ineffective for cocaine dependence.     

Withdrawal symptoms do not predict relapse among subjects treated for cannabis dependence

This is the first follow-up study on the association between cannabis withdrawal symptoms and risk of relapse to cannabis use. Withdrawal symptoms were assessed in 36 subjects seeking treatment for cannabis dependence. All were free of other substance use or alcohol abuse in the month before abstinence from cannabis. Follow-up was performed 26+/-4 months later, and at this point, the withdrawal symptoms were re-assessed. The following symptoms were significantly elevated after abstinence compared with follow-up: irritability, anger, depression, restlessness, craving, sleep problems, strange dreams, increased appetite, violent outbursts, sweating, hot flashes, chills, and shakiness. This offers further validation of a cannabis withdrawal syndrome. Average withdrawal scores at baseline did not differ with gender, age, treatment type, extent of cannabis use, or a lifetime history of anxiety or affective disorders. Withdrawal scores at baseline did not predict relapse during follow-up.     

Withdrawal symptoms in abstinent methamphetamine‐dependent subjects

Aims Withdrawal symptoms have been linked to a propensity for relapse to drug abuse. Inasmuch as this association applies to methamphetamine (MA) abuse, an understanding of the course of MA withdrawal symptoms may help to direct treatment for MA dependence. Previous studies of symptoms manifested during abstinence from MA have been limited in size and scope. We asked (i) whether debilitating psychological and/or physical symptoms appear during the first several weeks of MA abstinence, (ii) how craving for MA evolves and (iii) whether psychiatric symptoms (e.g. depression, psychosis) persist beyond a month of abstinence. Design A study of MA‐dependent participants, who initiated and maintained abstinence from the drug for up to 5 weeks, compared to a matched healthy comparison group. Setting In‐patient research hospital ward (MA‐dependent subjects) and out‐patient (comparison subjects). Participants Fifty‐six MA‐dependent and eighty‐nine comparison subjects. Measurements Rater‐assessed MA withdrawal questionnaire and self‐report assessment of craving (MA‐dependent subjects) and self‐report assessment of psychiatric symptoms (both groups). Findings At study entry, MA‐dependent subjects exhibited a wide range in severity of depressive symptoms, with the average score at a mild–moderate level of severity. Symptoms of psychosis were also prevalent. While depressive and psychotic symptoms largely resolved within a week of abstinence, craving did not decrease significantly from the time of initiating abstinence until the second week, and then continued at a reduced level to the fifth week. Conclusions Depressive and psychotic symptoms accompany acute withdrawal from methamphetamine but resolve within 1 week. Craving is also present and lasts at least 5 weeks.     

Six- and Twelve-Month Abstinence Rates in Inpatient Alcoholics Treated with Aversion Therapy Compared with Matched Inpatients from a Treatment Registry

Two hundred forty-nine patients who were treated for alcoholism in an inpatient multimodal treatment program that included aversion therapy were matched post hoc on 17 baseline variables with patients from a national treatment outcome registry. The latter patients received inpatient treatment that emphasized individual and group counseling as the primary therapeutic elements but did not include aversion therapy for alcohol. Six- and 12-month abstinence rates from alcohol and all mood-altering chemicals are reported. The patients treated with aversion therapy for alcohol had higher alcohol abstinence rates at 6 and 12 months (p less than 0.01). The abstinence rates from all mood-altering chemicals were higher in the aversion group at 6 months (p less than 0.05) but not at 12 months. The largest differences between treatment groups in 6-month alcohol abstinence rates were noted for males (p less than 0.001), those over 35 (p less than 0.001), daily drinkers (p less than 0.001), and those with alcohol-related work performance problems (p less than 0.05).     

Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence.

We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic.     

Prediction of treatment outcome by baseline urine cocaine results and self-reported cocaine use for cocaine and opioid dependence

This study examined the usefulness of baseline cocaine urine toxicology results and self-reported days of cocaine use in predicting treatment response in cocaine- and opioid-dependent subjects. Ninety-nine male and 52 female subjects, maintained on buprenorphine, participated in a 24-week, randomized, double-blind, four-cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had cocaine-positive and 49 (32%) cocaine-negative urines at the beginning of treatment. For the previous 30 days before study participation, 91 (60%) subjects reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%) subjects reported more than 15 days (high baseline cocaine use). By using the treatment effectiveness score (TES) as the outcome measure, a negative urine for cocaine at baseline predicted a better outcome during a 24-week trial for cocaine and opioid use. There also was a significant interaction between baseline cocaine urine results and desipramine response with the urine cocaine-negative group showing greater desipramine response than placebo for opioid and cocaine use. Self-reported cocaine use at baseline did not show significant predictive power for TES scores during the clinical trial. These results suggest that baseline cocaine urine results should be considered as stratifying variables in clinical trials for cocaine dependence.