Abstracts for Substance Abuse: Diagnosis and Treatment

Martell BA, O'Connor PG, Kerns RD, Becker WC, Morales KH, Kosten TR, Fiellin DA

Background: The prevalence, efficacy, and risk for addiction for persons receiving opioids for chronic back pain are unclear. Purpose: To determine the prevalence of opioid treatment, whether opioid medications are effective, and the prevalence of substance use disorders among patients receiving opioid medications for chronic back pain. Data Sources: English-language studies from MEDLINE (1966–March 2005), EMBASE (1966–March 2005), Cochrane Central Register of Controlled Clinical Trials (to 4th quarter 2004), PsychInfo (1966–March 2005), and retrieved references. Study Selection: Articles that studied an adult, nonobstetric sample; used oral, topical, or transdermal opioids; and focused on treatment for chronic back pain. Data Extraction: Two investigators independently extracted data and determined study quality. Data Synthesis: Opioid prescribing varied by treatment setting (range, 3% to 66%). Meta-analysis of the 4 studies assessing the efficacy of opioids compared with placebo or a nonopioid control did not show reduced pain with opioids (g, −0.199 composite standardized mean difference [95% CI, −0.49 to 0.11]; P = 0.136). Meta-analysis of the 5 studies directly comparing the efficacy of different opioids demonstrated a nonsignificant reduction in pain from baseline (g, −0.93 composite standardized mean difference [Cl, −1.89 to −0.03]; P = 0.055). The prevalence of lifetime substance use disorders ranged from 36% to 56%, and the estimates of the prevalence of current substance use disorders were as high as 43%. Aberrant medication-taking behaviors ranged from 5% to 24%. Limitations: Retrieval and publication biases and poor study quality. No trial evaluating the efficacy of opioids was longer than 16 weeks. Conclusions: Opioids are commonly prescribed for chronic back pain and may be efficacious for short-term pain relief. Long-term efficacy (> or = 16 weeks) is unclear. Substance use disorders are common in patients taking opioids for back pain, and aberrant medication-taking behaviors occur in up to 24% of cases.

Oslin DW, Berrettini WH, O'Brien CP

Alcohol dependence is one of the leading causes of morbidity worldwide, yet only a minority of those afflicted engages in treatment. While increasing access to treatment is an important public health approach, increasing the success of treatment is also likely to lead to greater engagement. However, alcohol dependence is a complex disorder likely to consist of several biological subtypes. Recent evidence from a number of different studies has suggested that genetic variation in the mu-opioid receptor has a significant influence on clinical presentation of alcohol problems and response to treatment with an opioid antagonist. Most notably, the A118G polymorphism of the mu-receptor gene has been demonstrated to predict clinical response to naltrexone in alcohol-dependent individuals. This article reviews the biological correlates and outlines a scientific agenda for better understanding the role of opioid neurotransmission in the etiology, maintenance and treatment of alcohol dependence.

Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A; COMBINE Study Research Group.

Context: Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. Objectives: To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. Design, Setting, and Participants: Randomized controlled trial conducted January 2001–January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. Interventions: Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. Main Outcome Measures: Percent days abstinent from alcohol and time to first heavy drinking day. Results: All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone × behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53–0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. Conclusions: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. Trial Registration: clinicaltrials.gov Identifier: NCT00006206.

Fals-Stewart W, Klostermann K, Yates BT, O'Farrell TJ, Birchler GR

The purpose of this study was to examine the clinical efficacy and cost effectiveness of brief relationship therapy (BRT), a shortened version of standard behavioral couples therapy (S-BCT), with alcoholic male patients (N = 100) and their nonsubstance-abusing female partners. Participants were randomly assigned to 1 of 4 treatment conditions: (a) BRT, (b) S-BCT, (c) individual-based treatment (IBT), or (d) psychoeducational attention control treatment (PACT). Equivalency testing revealed that, compared with those assigned to S-BCT, participants who were randomly assigned to BRT had equivalent posttreatment and 12-month follow-up heavy drinking outcomes. Moreover, at 12-month follow-up, heavy drinking and dyadic adjustment outcomes for patients who received BRT were superior to those of patients who received IBT or PACT. BRT was significantly more cost effective than the S-BCT, IBT, or PACT.

McKay JR, Lynch KG, Shepard DS, Pettinati HM

Context: Telephone-based disease management protocols have shown promise in improving outcomes in a number of medical and psychiatric disorders, but this approach to continuing care has received little study in alcohol- and drug-dependent individuals. Objective: To compare telephone-based continuing care with 2 more intensive face-to-face continuing care interventions. Design: A randomized 3-group clinical trial with a 2-year follow-up. SETTING: Two outpatient substance abuse treatment programs, one community-based and the other at a Veterans Affairs medical center facility. Patients: Alcohol- and/or cocaine-dependent patients (N = 359) who had completed 4-week intensive outpatient programs. Interventions: Three 12-week continuing care treatments: weekly telephone-based monitoring and brief counseling contacts combined with weekly supportive group sessions in the first 4 weeks (TEL), twice-weekly cognitive-behavioral relapse prevention (RP), and twice-weekly standard group counseling (STND). Main Outcome Measures: Percentage of days abstinent from alcohol and cocaine, total abstinence from alcohol and cocaine, negative consequences of substance use, cocaine urine toxicological results, and gamma-glutamyltransferase. Results: Participants in TEL had higher rates of total abstinence over the follow-up than those in STND (P<.05). In alcohol-dependent participants, 24-month gamma-glutamyltransferase levels were lower in TEL than in RP (P = .005). In cocaine-dependent participants, there was a significant group × time interaction (P = .03) in which the rate of cocaine-positive urine samples increased more rapidly in RP as compared with TEL. On percentage of days abstinent or negative consequences of substance use, TEL did not differ from RP or STND. Participants with high scores on a composite risk indicator, based on co-occurring alcohol and cocaine dependence and poor progress toward achieving intensive outpatient program goals, had better total abstinence outcomes up to 21 months if they received STND rather than TEL, whereas those with lower scores had higher abstinence rates in TEL than in STND (P = .04). Conclusions: Telephone-based continuing care appears to be an effective form of step-down treatment for most patients with alcohol and cocaine dependence who complete an initial stabilization treatment, compared with more intensive face-to-face interventions. However, high-risk patients may have better outcomes if they first receive group counseling continuing care after completing intensive outpatient programs.

Dackis CA, Kampman KM, Lynch KG, Pettinati HM, O'Brien CP

Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions, and the current study assessed whether modafinil would improve clinical outcome in cocaine-dependent patients receiving standardized psychosocial treatment. This was a randomized, double-blind, placebo-controlled trial conducted at a university outpatient center (from 2002 to 2003) on a consecutive sample of 62 (predominantly African American) cocaine-dependent patients (aged 25–63) free of significant medical and psychiatric conditions. After screening, eligible patients were randomized to a single morning dose of modafinil (400 mg), or matching placebo tablets, for 8 weeks while receiving manual-guided, twice-weekly cognitive behavioral therapy. The primary efficacy measure was cocaine abstinence based on urine benzoylecgonine levels. Secondary measures were craving, cocaine withdrawal, retention, and adverse events. Modafinil-treated patients provided significantly more BE-negative urine samples (p=0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (> or =3 weeks) of cocaine abstinence (p=0.05). There were no serious adverse events, and none of the patients failed to complete the study as a result of adverse events. This study provides preliminary evidence, which should be confirmed by a larger study, that modafinil improves clinical outcome when combined with psychosocial treatment for cocaine dependence.

Trenton AJ, Currier GW.

The use of anabolic androgenic steroids (AAS) for gains in strength and muscle mass is relatively common among certain subpopulations, including athletes, bodybuilders, adolescents and young adults. Adverse physical effects associated with steroid abuse are well documented, but more recently, increased attention has been given to the adverse psychiatric effects of these compounds. Steroids may be used in oral, 17alpha-alkylated, or intramuscular, 17beta-esterified, preparations. Commonly, steroid users employ these agents at levels 10- to 100-fold in excess of therapeutic doses and use multiple steroids simultaneously, a practice known as ‘stacking’. Significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse. Long-term steroid abusers may develop symptoms of dependence and withdrawal on discontinuation of AAS. Treatment of AAS abusers should address both acute physical and behavioural symptoms as well as long-term abstinence and recovery. To date, limited information is available regarding specific pharmacological treatments for individuals recovering from steroid abuse. This paper reviews the published literature concerning the recognition and treatment of behavioural manifestations of AAS abuse.

Gendel MH.

There is a broad range of forensic issues in addiction psychiatry. For many psychiatrists, what is most challenging about addressing these issues is their origin in the law, which is a system and a way of thinking that may feel foreign to the medical practitioner. To address forensic issues, addiction psychiatrists should learn and understand the specific legal questions that arise in each forensic context. They should become familiar with the relevant definitions, criteria, and legal requirements that apply in each specific area of their practice, rather than assume that clinical definitions and reasoning will carry them. If they perform forensic evaluations, addiction psychiatrists must distance themselves from the wish to help the examinee, focusing on the role of neutral examiner. Comfort and effectiveness with forensic issues require familiarity with, knowledge of, and ultimately respect for the forensic contexts of addiction psychiatric practice.

Galanter M, Dermatis H, Glickman L, Maslansky R, Sellers MB, Neumann E, Rahman-Dujarric C

Network therapy (NT) employs family members and/or friends to support compliance with an addiction treatment carried out in office practice. This study was designed to ascertain whether NT is a useful psychosocial adjunct, relative to a control treatment, for achieving diminished illicit heroin use for patients on buprenorphine maintenance. Patients agreeing to randomization to either NT (N = 33) or medication management (MM, N = 33) were inducted onto short-term buprenorphine maintenance and then tapered to zero dose. NT resulted in significantly more urine toxicologies negative for opioids than MM (65% vs. 45%) and more NT than MM patients (50% vs. 23%) experienced a positive outcome relative to secondary heroin use by the end of treatment. The use of NT in office practice may therefore improve the effectiveness of eliminating secondary heroin use during buprenorphine maintenance. It may also be useful in enhancing compliance with an addiction treatment regimen in other contexts.

DiClemente CC, Schlundt D, Gemmell L

Understanding the role of personal motivation in addiction treatment changed with the advent of the Transtheoretical Model of intentional behavior change, a better understanding of relapse, and a shift in focus from denial to readiness. Motivation is a complex concept that covers many diverse aspects of the process of intentional behavior change. This review examines current perspectives on readiness and the stages of change, criticisms and measurement issues, and clinical applications and future research in this area. Although significant challenges remain, properly incorporating the concepts of readiness and the stages of change into addiction treatment enables providers to address the diverse needs of substance abusers and treatment seekers, supports more proactive interventions, creates a concentration on motivational enhancement, and helps researchers understand the larger process of change where addict and treatment provider meet. Better measurement, more frequent assessments, and a better understanding of the stage subtasks and how they relate to readiness and successful change are needed to deepen our understanding of motivation and its role in the treatment of addiction.

Carroll KM, Fenton LR, Ball SA, Nich C, Frankforter TL, Shi J, Rounsaville BJ

Context: Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users. Objectives: To compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies-cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)-in reducing cocaine use. Design: Randomized, placebo-controlled, double-masked (for medication condition), factorial (2 × 2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT. Setting: A community-based outpatient substance abuse treatment program. Patients: A total of 121 individuals meeting the criteria for current cocaine dependence. Interventions: Patients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks. Main Outcome Measures: Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens. Results: Participants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo. Conclusions: Disulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.

Carmen B, Angeles M, Muñoz A, María AJ

Aims: To ascertain the efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence. Methods: Systematic review of the literature (1990–2002) and meta-analysis of full published randomized and controlled clinical trials assessing acamprosate or naltrexone therapy in alcohol dependence. Estimates of effect were calculated according to the fixed-effects model. Measurements: Relapse and abstinence rates, cumulative abstinence duration and treatment compliance were considered as primary outcomes. Findings: Thirty-three studies met the inclusion criteria. Acamprosate was associated with a significant improvement in abstinence rate [odds ratio (OR): 1.88 (1.57, 2.25), P < 0.001] and days of cumulative abstinence [WMD: 26.55 (17.56, 36.54]. Short-term administration of naltrexone reduced the relapse rate significantly [OR: 0.62 (0.52, 0.75), P < 0.001], but was not associated with a significant modification in the abstinence rate [OR: 1.26 (0.97, 1.64), P = 0.08]. There were insufficient data to ascertain naltrexone's efficacy over more prolonged periods. Acamprosate had a good safety pattern and was associated with a significant improvement in treatment compliance [OR: 1.29 (1.13, 1.47), P < 0.001]. Naltrexone's side effects were more numerous, yet the drug was nevertheless tolerated acceptably without being associated with a lower adherence to treatment (OR: 0.94 (0.80, 1.1), P = 0.5). However, overall compliance was relatively low with both medications. Conclusions: Both acamprosate and naltrexone are effective as adjuvant therapies for alcohol dependence in adults. Acamprosate appears to be especially useful in a therapeutic approach targeted at achieving abstinence, whereas naltrexone seems more indicated in programmes geared to controlled consumption. Both drugs are safe and acceptably tolerated but issues of compliance need to be addressed adequately to assure their usefulness in clinical practice.