Anti-social personality disorder and response to methadone maintenance treatment

A sample of 183 current methadone maintenance patients were interviewed on their drug use history, criminal history, current drug use, and symptoms of Anti-social Personality Disorder (ASPD). Thirty-nine percent of patients met the DSM-III-R criteria for a diagnosis of ASPD. ASPD patients had an earlier onset of drug use, drug injecting, heroin use, had wider polydrug using histories and had been arrested earlier and more frequently than other patients. Despite the different pretreatment histories of ASPD and other patients, there were no differences between the two groups in retention in treatment, methadone dosage or heroin use. It is concluded that heroin-dependent ASPD patients can be successfully retained in methadone treatment, on similar methadone doses and with similar in-treatment drug use patterns as those of non-ASPD heroin dependent patients.     

The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment?

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.     

Effects of chronic opioid dependence and HIV-1 infection on pattern shift visual evoked potentials

The goal of the present study was to examine the effects of opioid dependence, alone and in combination with asymptomatic HIV-1 infection, on the pattern shift visual evoked potential (PSVEP). For this purpose, three groups of patients were evaluated, including patients characterized by: (1) a past history (2–4 months abstinent) of DSM-IIIR opioid dependence (i.e. in partial remission); (2) a recent history (7 days abstinent) of opioid dependence with ongoing methadone maintenance; and (3) a recent history of opioid dependence, ongoing methadone maintenance, and asymptomatic HIV-1 infection. A group of healthy, non-drug dependent volunteers was also evaluated. Analyses revealed no PSVEP differences between patients with a past history of opioid dependence and healthy volunteers. There were also no PSVEP differences between methadone-maintained patients with or without HIV-1 infection. Collectively, however, the two methadone maintenance groups exhibited significant delays in the N75 and P100 components of the PSVEP relative to the other two groups. The delay in N75 latency was strongly correlated with self-reported years of heroin abuse, but not with years of cocaine, alcohol, or other drug abuse. These results are interpreted as reflecting an adverse effect of chronic opioid dependence on neural transmission within primary visual areas of the brain.     

Co-consumption of benzodiazepines in heroin users, methadone-substituted and codeine-substituted patients

Concomitant consumption of benzodiazepines (BZDs) and opioids is a major problem in patients with opioid dependence. It may have substantial impact on morbidity, mortality and clinical course. The current retrospective study aims to determine whether there are differences in the additional use of BZDs among addicts regularly taking methadone or codeine medications in treatment and untreated addicts injecting heroin. The records of 1,685 patients admitted for detoxification were analyzed using bivariate analysis and multiple logistic regression analysis. Demographic and drug related variables were considered, both as possible confounders and predictors of concomitant BZD use. Daily intake of BZDs was reported in 44.4% of the patients. Patients treated with methadone or codeine medications report daily intake of BZDs significantly more often than the heroin-dependent patients (p < 0.01).Using multiple regression analyses, the results were confirmed as independent from the assessed possible confounders. Further we found that daily use of alcohol or barbiturates, early onset of opioid use (p < 0.01), unemployment, having a substance dependent family member with, and a history of imprisonment (for all p < 0.05) were associated with concomitant daily consumption of BZDs in opioid dependent subjects. These finding underline the need to further explore the causes, interactions and consequences of concomitant BZD and opiate use.     

Buprenorphine for opioid dependence

In England and Wales, estimates suggest around 250,000 people have serious drug problems such as dependency, that cause considerable harm to themselves and others, and give rise to high social and economic costs. The number of people receiving specialist treatment for drug problems has increased greatly in recent years. Many people dependent on opioids will require opioid substitution treatment at some time. This may involve long-term maintenance to reduce use of illicit drugs, and/or short-term detoxification to stop such use completely. Standard management involves methadone maintenance therapy. Buprenorphine (Subutex-Schering-Plough) is also licensed for the management of patients with opioid dependence. Here we review the evidence for the use of buprenorphine compared with methadone for opioid dependence.     

Retention rate and illicit opioid use during methadone maintenance interventions: a meta-analysis

The efficacy of methadone maintenance in opioid addiction was assessed in terms of programme retention rate and reduction of illicit opioid use by means of a meta-analysis of randomised, controlled and double blind clinical trials. The results were compared with interventions using buprenorphine and levo-acetylmethadol (LAAM). Trials were identified from the PubMed database from 1966 to December 1999 using the major medical subject headings 'methadone' and 'randomised controlled trial'. Data for a total of 1944 opioid-dependent patients from 13 studies were analysed. Sixty-four percent of patients received methadone, administered either as fixed or adjusted doses. Thus, 890 patients received > or = 50 mg/day (high dose group) and 392 were given < 50 mg/day (low dose group). Of 662 controls, 131 received placebo, 350 buprenorphine (265 at doses > or = 8 mg/day and 85 at doses < 8 mg/day) and 181 LAAM. High doses of methadone were more effective than low doses in the reduction of illicit opioid use (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.26--2.36). High doses of methadone were significantly more effective than low doses of buprenorphine (< 8 mg/day) for retention rates and illicit opioid use, but similar to high doses of buprenorphine (> or = 8 mg/day) for both parameters. Patients treated with LAAM had more risk of failure of retention than those receiving high doses of methadone (OR 1.92, 95% CI 1.32--2.78). It is proposed that in agonist-maintenance programmes, oral methadone at doses of 50 mg/day or higher is the drug of choice for opioid dependence.     

Opiate Dependence,Comorbidity and Seasonality of Birth

Objective: In contrast with the non-opiate dependent population, persons biologically-dependent upon opioids display an excess life-time prevalence of affective and anxiety disorders. Many of these addicts state that opiates, particularly methadone, relieve or diminish the severity of their dysphoria. The purpose of this study is to explore this phenomena by analyzing how a specific population of long-term addicts (mean years of addiction 16.9, SD 3.8) differs from a non-opiate dependent population regarding seasonality of birth. Methods: Birth months were determined for 457 opiate dependent patients, placed onto methadone maintenance for intractable opiate dependence, born between 1930-1970 (sorted by sex, race, year and place of birth), and compared to normal US birth statistics. Affective and anxiety disorders were screened for using psychometric testing, verified by structured clinical interviews. Results: A significant difference was noted when comparing monthly births rates for patients and normals. Grouping the monthly data into birth trimesters (Oct- Jan; Feb-May; Jun-Sep) clearly shows this difference: opioid dependent persons--38.5/29.8/31.8%; normals--33.4/32.0/34.7%. As a group, intractable, opioid dependent patients demonstrate an increased lifetime prevalence, relative to normals, of anxiety (27.8 vs. 13.9%), dysthymia (23.4 vs. 6.4%) and combined anxiety+dysthymia (17.9 vs. 1.5%); opioid dependent persons born between Oct-Jan demonstrated more anxiety (32.0 vs. 25.1%), dysthymia (29.3 vs. 19.5) and combined anx+dys (23.3 vs. 14.4) than those born in the other two trimesters. Conclusion: Persons entering methadone maintenance for opiate dependence with comorbid anxiety, dysthymia or combined anxiety + dysthymia are more likely to have been born in the period of Oct-Jan. This may be due to a higher risk of developmental aberrations occurring in infants born during the light-limited portion of the year creating a later propensity for intractable, opiate dependence.     

Addiction Diagnostic Update: DSM-III-R Psychoactive Substance Use Disorders

Abstract

This article reviews the Community Reinforcement Approach (CRA) in the treatment of opioid dependence. It covers the use of CRA with both methadone maintenance patients and patients withdrawing from opioids. The data reviewed in the use of CRA in combination with methadone maintenance shows improvement in a number of areas. These include the reduction of opioid use, as well as other drugs of abuse, improved legal status, less psychiatric symptoms, and improved vocational and social functioning. CRA coupled with vouchers can assist in retaining patients in treatment long enough to improve opioid detoxification rates from buprenorphine and coupled with naltrexone may sustain abstinence. Further, the use of a standardized computerized format may extend the utility of CRA.     

Neuropsychological correlates of opioid dependence and withdrawal

Severity of opioid dependence, and performance on two successive runs of the Wisconsin Card Sorting Test (WCST), were assessed in 39 right-handed male and female methadone patients who had been randomly assigned to either a recently dosed (n=21) or 24 hr abstinent (n=18) condition. Results indicated that severity of opioid dependence was positively correlated with perseverative responses and errors on the second run of the WCST, p<.05. Further, controlling for the effect of dependence severity, patients in early methadone withdrawal made selectively more perseverative responses and errors than did recently dosed patients, p<.05, with no difference on nonperseverative errors. Findings were consistent with the hypothesis that opioid dependence, like alcoholism and cocaine addiction, is associated with disruption of executive cognitive functions mediated by the prefrontal cortex.     

Extended-release naltrexone for alcohol and opioid dependence: A meta-analysis of healthcare utilization studies

Through improved adherence, once-monthly injectable extended-release naltrexone (XR-NTX) may provide an advantage over other oral agents approved for alcohol and opioid dependence treatment. The objective of this study was to evaluate cost and utilization outcomes between XR-NTX and other pharmacotherapies for treatment of alcohol and opioid dependence. Published studies were identified through comprehensive search of two electronic databases. Studies were included if they compared XR-NTX to other approved medicines and reported economic and healthcare utilization outcomes in patients with opioid or alcohol dependence. We identified five observational studies comparing 1,565 patients using XR-NTX to other therapies over 6 months. Alcohol dependent XR-NTX patients had longer medication refill persistence versus acamprosate and oral naltrexone. Healthcare utilization and costs was generally lower or as low for XR-NTX-treated patients relative to other alcohol dependence agents. Opioid dependent XR-NTX patients had lower inpatient substance abuse-related utilization versus other agents and $8170 lower total cost versus methadone.     

Methadone combined with clonidine versus clonidine alone in opiate detoxification

The availability and use of a methadone/clonidine combination versus clonidine alone in opiate detoxification were studied. In Phase I of the study, a sequential combination of methadone followed by clonidine was utilized in those patients presenting with a primary diagnosis of opiate dependence. During the Phase II of the study, only clonidine was available. Medications were administered only if the history and clinical findings indicated impending or acute opiate withdrawal syndrome. Overall, there was no difference between the Phase I and Phase II groups when the number of opiate dependent admissions, patients completing detoxification, and the patients completing a follow-up rehabilitation program were compared. However, the patients in Phase I whose clinical symptomatology warranted the use of methadone were more likely to complete the detoxification program when compared to the patients in Phase II who received clonidine only. There was no difference between the two groups in completion of a follow-up rehabilitation. Detoxification with clonidine alone was more likely to be successful if the patient has had prior detoxification experience with methadone or if there was a secondary dependence of alcohol, sedative, or tranquilizer present coexisting with the primary opiate dependence diagnosis.     

Predictors of outcome in LAAM, buprenorphine, and methadone treatment for opioid dependence

This study examined (1) predictors of treatment outcome for opioid-dependent participants in a single-site controlled trial comparing methadone, buprenorphine, and LAAM treatments and (2) the extent to which various subpopulations of patients may have more successful outcomes with each medication. The relationships between patient demographics, drug use history, and psychological status and outcome measures of treatment retention, opiate use, and cocaine use were assessed. We believe this study to be the first to demonstrate that predictors of treatment success appear to be largely similar in LAAM, buprenorphine, and methadone treatment for opioid dependence. We did not find any factors that would strongly guide selection of one medication over others.     

Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone,buprenorphine or implant naltrexone

BackgroundIllicit opioid use is associated with high rates of fatal and non-fatal opioid overdose. This study aims to compare rates of fatal and serious but non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose.MethodsOpioid dependent patients treated with methadone (n = 3515), buprenorphine (n = 3250) or implant naltrexone (n = 1461) in Western Australia for the first time between 2001 and 2010, were matched against state mortality and hospital data. Rates of fatal and non-fatal serious opioid overdoses were calculated and compared for the three treatments. Risk factors associated with fatal opioid overdose were examined using multivariate cox proportional hazard models.ResultsNo significant difference was observed between the three groups in terms of crude rates of fatal or non-fatal opioid overdoses. During the first 28 days of treatment, rates of non-fatal opioid overdose were high in all three groups, as were fatal opioid overdoses in patients treated with methadone. However, no fatal opioid overdoses were observed in buprenorphine or naltrexone patients during this period. Following the first 28 days, buprenorphine was shown to be protective, particularly in terms of non-fatal opioid overdoses. After the cessation of treatment, rates of fatal and non-fatal opioid overdoses were similar between the groups, with the exception of lower rates of non-fatal opioid overdose in the naltrexone treated patients compared with the methadone treated patients. After the commencement of treatment, gender, and hospitalisations with a diagnosis of opioid poisoning, cardiovascular or mental health problems were significant predictors of subsequent fatal opioid overdose.ConclusionsRates of fatal and non-fatal opioid overdose were not significantly different in patients treated with methadone, buprenorphine or implant naltrexone. Gender and prior cause-specific hospitalisations can be used to identify patients at a high risk of fatal opioid overdose.     

Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence

BACKGROUND: Slow-release oral morphine (SROM) has been proposed as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence. However, the pharmacodynamics and pharmacokinetics of SROM have not been previously assessed in a methadone maintenance population. METHODS: In 14 methadone maintenance patients reporting adequate (holders, n=7) or inadequate (non-holders, n=7) withdrawal suppression between doses, plasma drug concentrations and indices of opioid effect (withdrawal severity, pupil diameter, and respiratory rate) were determined across a 24 h inter-dosing interval on one occasion at steady-state for methadone and SROM (once-daily Kapanol) using an open-label, crossover design. RESULTS: Opioid effects were of a similar overall magnitude following dosing for each drug and showed an inverse association with plasma drug concentrations, which peaked later for morphine compared to (R)-methadone (6.5 +/- 2.3 h vs. 2.5 +/- 1.4 h, P<0.001). For methadone non-holders, the number of self-reported opioid withdrawal symptoms prior to dosing was less for SROM compared to methadone (3.4 +/- 2.6 vs. 9.0 +/- 3.2, P<0.01); for holders it was approximately equal (4.4 +/- 3.0 vs. 4.0 +/- 3.7, P<0.76). Maintenance doses were more strongly related to plasma drug concentrations for SROM compared to methadone and may thus be more predictive of therapeutic response for the former medication. Twelve of the 14 subjects preferred SROM to methadone (P=0.01). CONCLUSIONS: The pharmacodynamics and pharmacokinetics of SROM support its use as an alternative once-daily agonist option in the treatment of opioid dependence, particularly for patients responding poorly to methadone maintenance treatment.     

Ketoconazole increases cocaine and opioid use in methadone maintained patients

Stress plays an important role in substance abuse problems. For example, in studies with rodents stress induces reinstatement of opioid and cocaine self-administration. In addition, attenuation of the stress response by pharmacological adrenalectomy using ketoconazole, a cortisol synthesis inhibitor, reduces cocaine self-administration in rodents. In contrast, studies in primates and humans have produced conflicting results using cortisol synthesis inhibitors for attenuating cocaine-related behaviors and subjective effects. To explore the treatment implications of these findings, ketoconazole's (600-900 mg daily) ability to reduce heroin and cocaine use was compared with placebo in 39 methadone maintained patients with a history of cocaine abuse or dependence during a 12-week double blind trial. Contrary to the predicted effects, both heroin and cocaine use increased after patients were stabilized on methadone and ketoconazole. Depressive and withdrawal symptoms improved no more with ketoconazole than with placebo treatment, and side effects were greater on ketoconazole than placebo. As reported before with methadone treatment, morning cortisol levels were significantly lower than normal values throughout the clinical trial, but were not lower with ketoconazole than placebo treatment. Thus, in agreement with the negative results from acute dosing studies in primates and humans, chronic ketoconazole treatment does not appear to reduce cocaine or opioid use in humans maintained on methadone.     

Buprenorphine: a controlled clinical trial in the treatment of opioid dependence

Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence.     

Mobile opioid agonist treatment and public funding expands treatment for disenfranchised opioid-dependent individuals

The New Jersey Medication Assisted Treatment Initiative (NJ-MATI) sought to reduce barriers to treatment by providing free, opioid agonist treatment (OAT, methadone or buprenorphine) via mobile medication units (MMUs). To evaluate barriers to OAT, logistic regression was used to compare opioid dependent patients enrolled in NJ-MATI to those entering treatment at fixed-site methadone clinics or non-medication assisted treatment (non-MAT). Client demographic and clinical data were taken from an administrative database for licensed treatment providers. The MMUs enrolled a greater proportion of African-American, homeless, and uninsured individuals than the fixed-site methadone clinics. Compared to non-MAT and traditional methadone clients, NJ-MATI patients were more likely to be injection drug users and daily users but less likely to have a recent history of treatment. These observations suggest that the patient-centered policies associated with NJ-MATI increased treatment participation by high severity, socially disenfranchised patients who were not likely to receive OAT.