Ivan D. Montoya

Improvement in naltrexone treatment compliance with contingency management

The efficacy of a voucher-based incentive program for improving adherence to outpatient, thrice weekly naltrexone maintenance was tested in a three group, randomized, 12-week clinical trial. Voucher incentives were given as follows: contingent group (n = 19) for each consecutive naltrexone dose ingested; non-contingent group (n = 19) on unpredictable schedule independently of taking naltrexone; no-voucher group (n = 20) none. Vouchers were exchangeable for goods and services. The contingent group had significantly longer treatment retention and ingested significantly more doses of naltrexone (consecutive and total) than either control group. Voucher incentives can significantly increase adherence to naltrexone maintenance in recently detoxified opioid dependent individuals.

Increasing opiate abstinence through voucher-based reinforcement therapy

Heroin dependence remains a serious and costly public health problem, even in patients receiving methadone maintenance treatment. This study used a within-subject reversal design to assess the effectiveness of voucher-based abstinence reinforcement in reducing opiate use in patients receiving methadone maintenance treatment in an inner-city program. Throughout the study subjects received standard methadone maintenance treatment involving methadone, counseling, and urine monitoring (three times per week). Thirteen patients who continued to use opiates regularly during a 5-week baseline period were exposed to a 12-week program in which they received a voucher for each opiate-free urine sample provided: the vouchers had monetary values that increased as the number of consecutive opiate-free urines increased. Subjects continued receiving standard methadone maintenance for 8 weeks after discontinuation of the voucher program (return-to-baseline). Tukeys posthoc contrasts showed that the percentage of urine specimens that were positive for opiates decreased significantly when the voucher program was instituted. (P < or = 0.01) and then increased significantly when the voucher program was discontinued during the return-to-baseline condition (P < or = 0.01). Rates of opiate positive urines in the return-to-baseline condition remained significantly below the rates observed in the initial baseline period (P < or = 0.01). Overall, the study shows that voucher-based reinforcement contingencies can decrease opiate use in heroin dependent patients receiving methadone maintenance treatment.

Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence

Buprenorphine is a partial μ‐opiate agonist and κ‐opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence.

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations

Abstract Terminology related to prescription drug misuse and abuse is inconsistently defined. An expert panel developed consensus classifications and definitions for use in clinical trials. Abstract As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment’s abuse potential.

Treatment of Tobacco Dependence in Mental Health and Addictive Disorders

People with mental health and addictive (MHA) disorders smoke at high rates and require tobacco treatment as a part of their comprehensive psychiatric care. Psychiatric care providers often do not address tobacco use among people with mental illness, possibly owing to the belief that their patients will not be able to quit successfully or that even short-term abstinence will adversely influence psychiatric status. Progress in the development of treatments has been slow in part because smokers with current MHA disorders have been excluded from most smoking cessation trials. There are several smoking cessation treatment options, including psychological and pharmacological interventions, that should be offered to people with an MHA disorder who smoke. Building motivation and readiness to quit smoking is a major challenge, and therefore motivational interventions are essential. We review the treatment options for people with tobacco dependence and MHA disorders, offer recommendations on tobacco assessment and tailored treatment strategies, and provide suggestions for future research. Treatment efficacy could be enhanced through promoting smoking reduction as an initial treatment goal, extending duration of treatment, and delivering it within an integrated care model that also aims to reduce the availability of tobacco in MHA treatment settings and in the community.

Cocaine use early in treatment predicts outcome in a behavioral treatment program.

In this evaluation of baseline drug use as a predictor of treatment outcome, cocaine use during a 5-week baseline was compared in methadone maintenance patients who had < 5 (n = 10) versus > or = 5 (n = 9) weeks of abstinence during an experimental cocaine abstinence reinforcement treatment. Cocaine use was evaluated at the 1st and last visit and the 1st and last week of baseline and as a mean across the 5-week baseline treatment; response was calculated as a mean across 12 weeks of experimental treatment. Those who had successful outcomes (abstainers) used significantly less cocaine in the 5-week baseline than those with less successful outcomes (nonabstainers). Differences in cocaine use were not evident in the 1st baseline visit or week, but the abstainers used significantly less cocaine in the last visit and week of baseline compared with the nonabstainers. Cocaine use during baseline provided critical predictors of response to the experimental treatment.

Psychological treatments for stimulant misuse, comparing and contrasting those for amphetamine dependence and those for cocaine dependence.

Purpose of review The aim is to compare and contrast psychological treatments for amphetamine and cocaine dependence. Recent findings Stimulant dependence, in the form of cocaine or amphetamine/methamphetamine dependence, is prevalent worldwide, and their ratio may vary across different countries and regions of countries. The treatment of stimulant disorders has greatly advanced in recent years, and scientific evaluation of behavioral therapies, using randomized clinical trials designs and a stage-wise approach, have demonstrated the safety and efficacy of interventions. Psychological interventions such as cognitive behavioral therapy and contingency management for cocaine and methamphetamines use disorders are well tolerated and moderately effective in achieving drug abstinence. There is evidence that contingency management interventions can help to improve retention in treatment and, in turn, other treatment outcomes. Although there are important differences in the neuropsychiatric and medical consequences of cocaine and amphetamine use disorders, there is currently no evidence for a differential treatment effect of any psychosocial treatment in the management of these disorders. Summary As there are no Food and Drug Administration-approved medications for the treatment of these disorders, psychological interventions form the basis of their treatment. More research is needed to address the specific psychosocial needs of cocaine and amphetamine-dependent individuals in order to improve their treatment outcomes.

Generalizability of clinical trials for cannabis dependence to community samples.

There is growing concern that results of tightly controlled clinical trials may not generalize to broader community samples. To assess the proportion of community dwelling adults with cannabis dependence who would have been eligible for a typical cannabis dependence treatment study, we applied a standard set of eligibility criteria commonly used in cannabis outcome studies to a large (N=43,093) representative US adult sample interviewed face-to-face, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Approximately 80% of the community sample of adults with a diagnosis of cannabis dependence (N=133) would be excluded from participating in clinical trials by one or more of the common eligibility criteria. Individual study criteria excluded from 0% to 41.0% of the community sample. Legal problems, other illicit drug use disorders, and current use of fewer than 5 joints/week excluded the largest percentage of individuals. These results extend to cannabis dependence concerns that typical clinical trials likely exclude most community dwelling adults with the disorder. The results also support the notion that clinical trials tend to recruit highly selective samples, rather than adults who are representative of typical patients. Clinical trials should carefully evaluate the effects of eligibility criteria on the generalizability of their results. Even in efficacy trials, stringent exclusionary criteria could limit the representativeness of study results.

Double-blind comparison of carbamazepine and placebo for treatment of cocaine dependence

This study was conducted to determine the effectiveness of carbamazepine (CBZ) for treatment of cocaine dependence. Sixty-two (CBZ = 28, placebo = 34) cocaine-dependent (DSM-III-R criteria) volunteers consented to be treated for eight weeks with standardized outpatient individual counseling twice a week plus double-blind CBZ or inactive placebo. During the 8-week trial, both groups showed increased number of urine samples negative for cocaine, significantly (P < 0.01) decreased self-reported cocaine use (money spent and grams used), and decreased Beck Depression Inventory and Symptom Check List-90-Revised (SCL-90-R) total scores. However, there were no significant differences between CBZ and placebo. This study does not support the effectiveness of CBZ for outpatient treatment of cocaine dependence.

A Phase 3 Placebo-Controlled, Double Blind, Multi-Site Trial of the alpha-2-adrenergic Agonist, Lofexidine, for Opioid Withdrawal

CONTEXT Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. OBJECTIVE To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. DESIGN An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11). SUBJECTS Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. MAIN OUTCOME MEASURE Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). RESULTS Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). CONCLUSIONS Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.