Maria A. Sullivan

Treatment of depression in patients with opiate dependence

Depression is common among opiate-dependent patients and has been associated with worse prognosis. This article reviews the literature on treatment of depressive disorders and symptoms among patients with opiate dependence. Depression bears a complex relationship to opiate dependence and may represent an independent disorder or may be engendered by psychosocial stress or toxic and withdrawal effects of drugs. Primary treatments for opiate dependence (e.g., methadone or buprenorphine maintenance or residential treatment) are associated with substantial improvements in depression. Studies of antidepressant medications have produced mixed results, some positive but more negative. It is not clear what accounts for these differences, and more research is needed to determine how to select opiate-dependent patients most likely to benefit from antidepressants. Fewer studies have examined psychosocial or behavioral interventions, but some of these also show promise. The data suggest a stepped model of care in which depression is evaluated and observed during the outset of treatment for opiate dependence and if it does not improve, specific psychosocial interventions or antidepressant medications tried. Research is needed on such integrated models of care and treatment algorithms to determine their efficacy and cost effectiveness.

Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers.

Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as ‘I feel a good drug effect’ and ‘I like the drug.’ In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine⩾heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of ‘I feel a bad drug effect’ and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

Advances in Non-Nicotine Pharmacotherapy for Smoking Cessation

Progress in understanding the pharmacological nature of tobacco addiction, along with the modest success rates achieved by the nicotine replacement therapies, has provided the major impetus for the development of non-nicotine drugs as smoking cessation aids. This article reviews evidence from controlled trials of several non-nicotine medications for the treatment of nicotine dependence.Clonidine was the first non-nicotine medication to show efficacy for smoking cessation in multiple studies, but its effect was found to be limited at best. Positive results across several trials have been consistently demonstrated for amfebutamone (bupropion). Encouraging results have also been observed for nortriptyline and moclobemide. Studies of combined treatments using non-nicotine medications (amfebutamone, mecamylamine, oral dextrose) with nicotine replacement therapy suggest increased efficacy relative to treatments using one or the other treatment strategy alone.Thus, available evidence indicates that non-nicotine drug treatments offer a promising panoply of therapeutic strategies for the addicted smoker.

Behavioral naltrexone therapy: An integrated treatment for opiate dependence

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.

Uses of Coercion in Addiction Treatment: Clinical Aspects

Coerced or involuntary treatment comprises an integral, often positive component of treatment for addictive disorders. By the same token, coercion in health care raises numerous ethical, clinical, legal, political, cultural, and philosophical issues. In order to apply coerced care effectively, health care professionals should appreciate the indications, methods, advantages, and liabilities associated with this important clinical modality. An expert panel, consisting of the Addiction Committee of the Group for the Advancement of Psychiatry, listed the issues to be considered by clinicians in considering coerced treatment. In undertaking this task, they searched the literature using Pubmed from 1985 to 2005 using the following search terms: addiction, alcohol, coercion, compulsory, involuntary, substance, and treatment. In addition, they utilized relevant literature from published reports. In the treatment of addictions, coercive techniques can be effective and may be warranted in some circumstances. Various dimensions of coercive treatment are reviewed, including interventions to initiate treatment; contingency contracting and urine testing in the context of psychotherapy; and pharmacological methods of coercion such as disulfiram, naltrexone, and the use of a cocaine vaccine. The philosophical, historical, and societal aspects of coerced treatment are considered.

Behavioral Therapy to Augment Oral Naltrexone for Opioid Dependence: A Ceiling on Effectiveness?

The effectiveness of antagonist maintenance with oral naltrexone for opioid dependence has been limited by high dropout rates. Behavioral Naltrexone Therapy (BNT) was developed to improve retention on oral naltrexone by integrating voucher incentives, Motivational and Cognitive Behavioral therapies, and a significant other for monitoring medication adherence. In a 6-month, randomized, controlled trial in heroin dependent patients, BNT (N = 36) improved retention in treatment compared to a standard treatment control (Compliance Enhancement (CE); N = 33) (log rank = 4.28; p = .04). Most patients retained beyond 3 months achieved abstinence from opioids, but retention at 6 months was only 22% on BNT and 9% on CE. A systematic review of related controlled trials revealed similar effect sizes in the small to medium range, and substantial dropout. There may be a limit on the extent to which behavioral therapy can overcome poor adherence to oral naltrexone. Future research should consider combinations of behavioral methods with new long-acting injectable or implantable naltrexone formulations.

Predictors of Retention in Naltrexone Maintenance for Opioid Dependence: Analysis of a Stage I Trial

Behavioral naltrexone therapy (BNT) was developed to address the shortcomings of naltrexone maintenance for opiate dependence and improve compliance by integrating several empirically validated methods, including the use of a significant other to monitor compliance, voucher incentives, and motivational techniques. An uncontrolled Stage I pilot trial (N = 47) of BNT was conducted. Baseline demographic and clinical variables were evaluated as predictors of retention with univariate tests. Significant predictors were entered together into a multiple regression model. Poorer (shorter) retention in treatment was associated with methadone use and higher average bags per day of heroin. Other variables that became non-significant in multiple regression analysis included older age and depressive symptoms. Individuals with greater physiologic dependence and/or dependence on longer-acting opiates are at higher risk to drop out from naltrexone maintenance and may require a more gradual detoxification and more intensive behavioral therapy aimed at enhancing initial compliance.

Prescription Drug Abuse: Epidemiology, Regulatory Issues, Chronic Pain Management with Narcotic Analgesics

The epidemic of prescription drug abuse has reached a critical level, which has received national attention. This article provides insight into the epidemiology of prescription drug abuse, explains regulatory issues, and provides guidelines for the assessment and management of pain, particularly with long-term opioid therapy. Using informed consent forms, treatment agreements, and risk documentation tools and regularly monitoring the 4 As help to educate patients and guide management based on treatment goals. By using universal precautions, and being aware of aberrant behaviors, physicians may feel more confident in identifying and addressing problematic behaviors.

A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders.

AIM To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. DESIGN This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. SETTINGS The trial was conducted at two university research centers in the United States. PARTICIPANTS One hundred and three cannabis-dependent adults participated in the trial. MEASUREMENTS The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. FINDINGS The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P < 0.01; odds ratio = 4.51, 95% confidence interval: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F1,179  = 30.49, P < 0.01), but not the VEN-XR group (F1,186  = 0.02, P = 0.89). CONCLUSIONS For depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use.

Sex differences and hormonal influences on response to mechanical pressure pain in humans.

UNLABELLED Previous studies have demonstrated that sex differences in pain responsivity can be detected using various models of experimentally induced pain. The present study employed the mechanical pressure test in order to examine potential differences in pain report among men, normally menstruating women (NMW), and women taking monophasic oral contraceptives (OCW). Testing occurred during 5 phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) and all participants completed 10 sessions (2 sessions per phase). Menstrual-cycle phase was estimated for OCW based on their first day of menses. Men were tested at time points that roughly corresponded to the intervals during which the different phases occurred in NMW. During the mechanical pressure test, 4 different weights were placed on the fingers, one at a time, and ratings of pain were recorded for 30 seconds. The statistical decision-making model and a forced-choice procedure were used to analyze the response data. Two variables, based on signal detection theory, were thus generated: P(A), a measure of sensory pain, and B, a measure of response bias. P(A) is believed to be a measure of pain sensitivity while B measures stoicism. NMW tended to report lower P(A) values, indicating reduced ability to discriminate among different stimulus intensities, during the menstrual and late luteal phases compared to the luteal phase. OCW reported lower B values, indicating less stoicism, during the menstrual compared to the follicular and ovulatory phases. Men tended to have significantly lower B values than OCW, but not NMW. These results demonstrate subtle menstrual-cycle effects in NMW and OCW. Sex differences were few, with more group differences and trends emerging between OCW and men, as opposed to men and NMW. PERSPECTIVE The lack of consistent differences between men and NMW underscores the subtle impact of sex and hormonal changes in pain report. In addition, the data obtained in NMW support the notion that changes in hormone levels during the menstrual cycle can lead to changes in pain responsivity as NMW had trends for better discrimination in menstrual phases when estradiol levels were highest.