Annie Umbricht

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.

Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Therapeutic drug monitoring in methadone maintenance: choosing a matrix.

Abstract Methadone maintenance is the premier pharmacological treatment for opioid addiction, but it is rarely informed by evidence-based practice guidelines for dosage monitoring and adjustment. Such guidelines are crucial because the pharmacokinetics of methadone vary greatly among patients, and this variation may account for differences in treatment outcome. We review the pharmacokinetics of methadone and factors that may alter it (including drug interactions, disease states, and idiosyncratic differences among patients). Also reviewed are prospects for therapeutic drug monitoring (TDM) of methadone in plasma, urine, sweat, and saliva. Due to its ease of collection and its presumed representation of the bioavailable free-fraction of methadone, saliva may be a promising matrix. However, saliva methadone concentrations are influenced by salivary pH, and future studies are needed to determine how to control for that. Administrative, medical, and social implications of methadone TDM are briefly discussed.

Abstinence reinforcement maintenance contingency and one-year follow-up.

BACKGROUND Relapse to drug use is often seen when contingencies designed to reduce drug use are discontinued. This paper reports on a stepdown maintenance contingency and 1-year follow-up in 110 patients who were maintained on methadone (50 or 70 mg/day) and who had completed a contingency management trial targeted to decreasing their opiate use. In the prior study (induction phase, 8 weeks) participants received vouchers for each opiate-negative urine screen or noncontingently. METHODS In this study (maintenance phase, 12 weeks), participants were rerandomized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens (N=55) or noncontingently (N=55). Since participants had been rerandomized from induction-phase contingencies, most study data were analyzed as if from a 2 x 2 (inductionxmaintenance) design. Follow-up interviews were conducted at 3, 6, and 12 months after study participation. RESULTS Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial. Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study. Significantly more participants in the maintenance contingency group transferred directly to another methadone program. CONCLUSION These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance.

Family history influence on drug abuse severity and treatment outcome

Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment.

A laboratory study of hydromorphone and cyclazocine on smoking behavior in residential polydrug users

The effects of cyclazocine and hydromorphone on spontaneous and laboratory cigarette smoking were compared in a double-blind, placebo-controlled, crossover study. Participants (seven men, one woman) received oral doses of placebo, cyclazocine (0.2, 0.4, and 0.8 mg) and hydromorphone (5 and 15 mg) in a randomized order on experimental days. Spontaneous smoking was recorded during two intervals on the experimental days: a 3-h period 5-8 h after drug administration (Interval 1), and the rest of the day (Interval 2). Measures of smoking topography and subjective and physiologic effects of a single cigarette were obtained on the experimental days. Neither hydromorphone nor cyclazocine significantly changed spontaneous smoking when compared to the placebo condition; however, compared to hydromorphone (5 mg), cyclazocine (0.4 and 0.8 mg) decreased spontaneous smoking during Interval 1. Hydromorphone (5 and 15 mg) and cyclazocine (0.4 and 0.8 mg) diminished smoking-induced increases in heart rate. Compared to the placebo condition, cyclazocine (0.2 and 0.4 mg) reduced exhaled carbon monoxide (CO) boost, a measure of smoke exposure. Further studies of the effects of kappa opioid agonists on smoking behavior may lead to a better understanding of the role of opiates in smoking behavior.

Do noncontingent vouchers increase drug use

Data from 2 contingency management trials, targeting opiate or cocaine use, were used to investigate whether noncontingent vouchers inadvertently reinforce drug use. The control group in each trial received noncontingent vouchers matched in value and frequency to those received by experimental groups, but independent of urinalysis. Vouchers were offered thrice weekly for 8 weeks (opiates) or 12 weeks (cocaine). Both dose-response and temporal associations of noncontingent voucher receipt with drug-positive urines were assessed. Drug use was unrelated to frequency of noncontingent voucher delivery and noncontingent voucher receipt when being drug positive was unassociated with risk of subsequent drug use, with one exception: cocaine use in the cocaine study (relative risk = 1.05, 95% confidence interval: 1.01-1.09). Overall, results do not indicate a causal relationship between noncontingent voucher receipt and increased drug use.

Gender Differences in Indices of Opioid Dependency and Medical Comorbidity in a Population of Hospitalized HIV-Infected African-Americans

We examined gender differences in drug use patterns and in medical presentation among 520 hospitalized, HIV-infected African-Americans. Substance abuse history was self-reported, and medical data were obtained by chart review. Overall, 321 (65%) reported ever having used heroin, with equivalent rates in men and women. Women were more likely to report current use, to have sought treatment, and tended to feel more dependent on heroin than men. Among heroin users, women were more likely to be admitted for conditions related to drug use, rather than AIDS, and to have CD4 counts > 200/mm3. These gender differences in opioid dependency and medical comorbidity may indicate a need for alternative treatment approaches for men and women.

Buprenorphine for Human Immunovirus-Positive Opiate-Dependent Patients

To the Editor: Buprenorphine is a semisynthetic opioid agonist/antagonist under research for treatment of opiate and opiate plus cocaine dependence. It is safe, has low abuse/dependence liability, can be administered sublingually, and prevents opiate withdrawal while blocking the effect of street opiates (Lewis 1989; Jasinski et al 1989; Johnson el at 1992; Kosten et al 1989, 1991; Mello et al 1989). Our group is conducting a series of studies to determine the safety and effectiveness of buprenorphine for the maintenance and detoxification of opiate dependent individuals. As part of these studies, research participants are voluntarily tested for human immunovirus (HIV). The result of the test does not influence their participation in the studies. We report here the safety and efficacy of buprenorphine for an 8-day inpatient detoxification of HIV-positive opiate dependent Diagnostic and Statistical Manual of Mental Disorders, 3rd ed, revised ([DSM-IIIR], criteria) research participants. The sublingual buprenorphine/placebo daily dose was: 4 mg (day 1), 6 mg (day 2), 4 mg (day 3), 2 mg (day 4), and 0 mg (days 5−8). From a total sample of 26 patients tested for HIV, there were 2 (7.7%) whose results were positive. These two patients were African-American men, ages 40 and 41. They had completed high school, one was employed full-time and the other was unemployed. They reported daily use of heroin, had a history of more than 10 years of heroin use, and had received previous drug abuse treatments. They also reported regular use of alcohol and cocaine. Their preferred route of opiate administration was snorted, although both had a history of intravenous drug use. They had no history of legal problems and were not living with a sexual partner. One patient had cervical and inguinal adenopathy, a toe fungus, and lymphocyte surface marker (T4) of 113/mm3; the other was asymptomatic. These patients did not differ in their psychosocial and drug use histories from the other patients who were HIV-negative. The two patients completed the 8-day inpatient treatment, tolerated the medication, and experienced no serious side effects. One patient complained of mild constipation at the beginning of treatment. They did not require additional medication to help suppress opiate withdrawal and they did not use any other opiates throughout this treatment. Both patients reported reduction in the Addiction Research Center Inventory (ARCI) opiate withdrawal scale and Clinical Investigation Narcotic Assessment (CINA) scores. The medical examination, blood chemistry and hematology, and electrocardiogram (ECG) did not show differences between admission and discharge. These results suggest that buprenorphine is a safe and useful medication for short-term detoxification of opiate-dependent individuals who are HIV positive or have acquired immunodeficiency syndrome (AIDS). Treatment of opiate dependence can also help to prevent the transmission of the virus. Further research is needed to establish fully the safety and efficacy of buprenorphine for the treatment of opiate-dependent individuals who have HIV infection.