Jennifer Casarella

Benefits of retention in methadone maintenance and chronic medical conditions as risk factors for premature death among older heroin addicts.

Background Methadone maintenance treatment reduces rates of premature mortality in heroin addicts. However, few published studies have addressed the effectiveness of treatment, mortality rates, or causes of death in older (geriatric) patients maintained on methadone. Identifying risk factors for premature mortality and potential targets for early intervention may reduce rates of premature mortality in older patients maintained on methadone. Methods We conducted a retrospective chart review for patients enrolled in the methadone maintenance program at the Atlanta Veterans Affairs Medical Center. We reviewed the charts of 91 patients and collected the following information: demographics (age, gender, marital status, and race); composite score at admission on the Addiction Severity Index (ASI); most recent ASI score for alcohol use, drug use, and medical, psychiatric, family, legal, and employment problems; results of urine drug screens for opiates, cocaine, and benzodi-azepines (first 4 screens after admission and last 4 screens); dose and duration of methadone treatment; HIV and hepatitis B and C status; tobacco smoking; presence of diabetes mellitus, hypertension, heart disease, chronic obstructive pulmonary disease, or cancer; history of intravenous drug use; andmissed primary care appointments (last five appointments). Results A statistically significant association was found between diabetes mellitus and between liver and gastrointestinal cancer and premature mortality in this sample of older patients maintained on methadone (OR=30.79, P=0.008 for diabetes mellitus; OR=19.91, P=0.017 for cancer). Patients who remained in treatment showed statistically significant improvement in ASI scores for problems related to drug use and for psychiatric, medical, and legal problems. They showed a nonsignificant trend toward reduction of problems associated with alcohol use. The group of patients who dropped out of methadone treatment did not show statistically significant improvement on any area of the ASI except family problems. The group who remained in treatment also showed a statistically significant reduction in drug use when results of the first four and last four urine drug screens for opiates, cocaine, and benzodiazepines were compared (P<0.0001 for opiates and cocaine, P=0.02 for benzodiazepines).On the other hand, the group who dropped out of methadone treatment did not show any statistically significant reduction in drug use based on urine screens (P=0.05 for opiates, P=0.38 for cocaine, and P=0.53 for benzodiazepines). Conclusions The results presented here suggest potential targets for intervention related to lifestyle risk factors and comorbid medical conditions, such as nicotine dependence and diabetes mellitus, that may have the potential to improve health outcomes for older patients with opioid dependence.

Methadone maintenance dosing guideline for opioid dependence, a literature review.

ABSTRACT To date, methadone dosing is still an issue of debate and controversy among clinicians who are involved in methadone maintenance programs. The authors conducted a literature review to update clinicians about this issue and provide recommendations for proper methadone dosing. Studies eligible for inclusion in the review were retrieved from the PubMed database by searching for reports published between 1990 and September 2008 using the major medical subject headings Methadone (all fields) and dose. Only articles written in English were included. Additional reports were identified from the reference lists of retrieved articles and by manual review of the tables of contents of journals on drug of abuse included in the psychiatry and substance abuse subject category listing 2008 of the Journal Citation Reports. Abstracts of medical meetings were excluded. Twenty-four articles were included in the review. Twelve are randomized, controlled, or double-blind clinical trials, 10 are non-randomized and observational studies, and 2 are meta-analyses. Currently, the consensus is to have a goal for methadone dosing in the range of 60 to 100 mg daily. For patients who continue to use illicit opiates while prescribed this dose range, clinicians may consider doses greater than 100 mg daily. However, this is not the current consensus but rather is based on the limited promising data the authors have; it could be considered if the benefits outweigh the risks for some patients.

Effect of Methadone Maintenance Treatment on Heroin Craving, a Literature Review

ABSTRACT Despite agreement that methadone maintenance treatment (MMT) is an effective and safe option for treatment of heroin dependence, there have been controversies about its effect on heroin craving. A systematic literature review of the PubMed database was used to find studies eligible for inclusion in the study. The authors present the results of 16 articles that met all inclusion criteria. Overall, 7 studies reported that methadone could reduce heroin craving, 4 studies reported that patients in MMT are still at risk of having heroin craving, 1 study reported that methadone could increase heroin craving, and 4 studies reported that methadone has a neutral effect on heroin craving. One may speculate from these data that methadone may help with heroin craving, but patients in MMT may still be at risk of cue-induced heroin cravings. Methadone provides a helpful tool for reducing some components of craving and risk of relapse for patient receiving MMT.

Effect of Buprenorphine Dose on Treatment Outcome

The goal of this meta-analysis is to provide evidence based information about proper dosing for buprenorphine maintenance treatment to improve treatment outcome. To be selected for the review and inclusion in the meta-analysis, articles had to be randomized, controlled, or double-blind clinical trials, with buprenorphine as the study drug; the length of buprenorphine maintenance treatment had to be 3 weeks or longer; doses of buprenorphine had to be clearly stated; outcome measures had to include retention rates in buprenorphine treatment; outcome measures had to include illicit opioid use based on analytical determination of drugs of abuse in urine samples as outcome variables; and outcome measures had to include illicit cocaine use based on analytical determination of drugs of abuse in urine samples as outcome variables. Twenty-nine articles were excluded because they did not meet the inclusion criteria. The authors present the results of 21 articles that met inclusion criteria. The higher buprenorphine dose (16–32 mg per day) predicted better retention in treatment compared with the lower dose (less than 16 mg per day) (P = .009, R2 adjusted = 0.40), and the positive urine drug screens for opiates predicted dropping out of treatment (P = .019, R2 Adjusted = 0.40). Retention in treatment predicted less illicit opioid use (P = .033, R2 Adjusted = 0.36), and the positive urine drug screens for cocaine predicted more illicit opioid use (P = .021, R2 Adjusted = 0.36). Strong evidence exists based on 21 randomized clinical trials that the higher buprenorphine dose may improve retention in buprenorphine maintenance treatment.

High Dose versus Moderate Dose Methadone Maintenance: Is There a Better Outcome?

ABSTRACT Methadone dosing has been an issue of controversy among clinicians for a long time. Few recent studies reported that doses above 100 mg daily seem promising in better control of illicit opiate use for some patients, but more research is needed to support that notion. A retrospective chart review for patients maintained on methadone at Atlanta Veterans Affairs Medical Center was conducted. Patients were categorized into two groups: patients on a methadone dose of 60 to 100 mg daily (n = 34) and patients on a methadone dose greater than 100 mg daily (n = 25). Those charts were compared for urine drug screens for opiates and cocaine (first four from admission and most recent four screens), retention or drop out from the program, and Addiction Severity Index (ASI) composite score at admission and most recent score. The results of the first and last four urine drug screens for opiates showed that the moderate dose group was positive 23% and 17%, respectively. However, the high dose group was positive 14% and 8%, respectively. These results showed statistical significance (Chi-Square = 8.04, df = 3 and p =.03). ASI scores for drugs did not show statistically significant improvement for the moderate dose group (p =.19) but showed statistically significant improvement for the high dose group (p =.0002) when the result of the first and last ASI scores among each group were compared. The ASI scores for family problems showed statistically significant improvement for the moderate dose group (p =.03). High doses of methadone greater than100 mg daily may provide a better outcome for illicit opiate use among some patients who would not respond to moderate doses.

Heroin anticraving medications: A systematic review

Background: Heroin craving is a trigger for relapse and dropping out of treatment. Methadone has been the standard medication for the management of heroin craving. Objectives: We explored the medication options other than methadone which may have heroin anticraving properties. Methods: To be selected for the review, articles had to include outcome measures of the effect of the studied medication on subjective and/or objective opiate craving and be of the following two types: (1) randomized, controlled, and/or double-blind clinical trials (RCTs) examining the relationship between the studied medication and heroin craving; (2) nonrandomized and observational studies (NRSs) examining the relationship between the studied medication and heroin craving. Thirty-three articles were initially included in the review. Twenty-one were excluded because they did not meet the inclusion criteria. We present the results of 12 articles that met all the inclusion criteria. Results: Some new medications have been under investigation and seem promising for the treatment of opiate craving. Buprenorphine is the second most studied medication after methadone for its effect on opiate craving. At doses above 8 mg daily, it seems very promising and practical for managing opiate craving in patients receiving long-term opioid maintenance treatment. Conclusions and Scientific Significance: In doses higher than 8 mg daily, buprenorphine is an appropriate treatment for opiate craving. More research with rigorous methodology is needed to study the effect of buprenorphine on heroin craving. Also more studies are needed to directly compare buprenorphine and methadone with regard to their effects on heroin craving.

Onsite QTc Interval Screening for Patients in Methadone Maintenance Treatment

ABSTRACT To improve the electrocardiogram screening process and early detection of patients at high risk for cardiac arrhythmias, the authors created a model in their clinic where they provided an onsite electrocardiogram screening that might be feasible and practical. The authors then performed a retrospective chart review to access the efficacy and feasibility of their new onsite procedure in identifying methadone maintained patients at high risk for cardiac arrhythmias. Records from all patients who are currently or had previously been maintained on methadone in the methadone maintenance program at the Atlanta VA Medical Center between 2002 and 2009 were evaluated. Of the 140 patients treated at the clinic between 2002 and 2009, 85 were excluded from the study because they had been treated as guests (had been in treatment in other clinics but received methadone dosing temporarily from our clinic), were treated in the clinic for less than 6 months, or dropped out of treatment. Thus, 55 patient charts were selected for review. Most patients (95%) received baseline and annual electrocardiogram screening. The average baseline QTc was (417 ± 30) and most recent QTc (442 ± 25). This QTc prolongation from baseline showed statistical significance (P < .0001). Sixty-seven percent of patients had statistically significant QTc prolongation from baseline but was less than 450 ms (mean: 428 ± 16, P = .008). Twenty-seven percent of patients had statistically significant QTc prolongation from baseline of more 450 ms but was less than 500 ms (mean: 460 ± 8, P < .0001). Six percent of patients had statistically significant QTc prolongation from baseline of more 500 ms (mean: 503 ± 1.15, P = .027). Recent cocaine use was the only individual variable that showed statistically significant correlation with QTc prolongation (F = 6.98, P = .01). The authors demonstrated in this study that providing an onsite electrocardiogram screening with a focus on patient education and limiting the referral to specialty care for patients at high risk for cardiac arrhythmias could be practical and feasible.

Comparison of QTc Interval Prolongation for Patients in Methadone Versus Buprenorphine Maintenance Treatment: A 5-Year Follow-Up

The authors investigated whether patients receiving buprenorphine maintenance treatment (BMT) will have corrected QT (QTc) prolongation after taking buprenorphine for an extended period of time. They also compared QTc prolongation for patients in methadone maintenance treatment (MMT) versus BMT to determine which medication is the better option for patients with heart disease. A retrospective chart review study of 73 patients in BMT and 55 patients in MMT was performed. A linear regression model with a one-sided P value was used for data analysis. The MMT group had statistically significant prolongation of QTc compared with the BMT group (F = 3.94, P = .0001). Being diagnosed with congestive heart failure and taking methadone were the only individual variables that showed a statistically significant association with a QTc prolongation > 500 ms. The model as a whole showed statistical significance (F = 5.203, P = .007). Being diagnosed with congestive heart failure was the only individual variable that showed a statistically significant association with mortality. The model as a whole also showed statistical significance (F = 17.15, P = .000). This study supports previous findings that methadone may be associated with QTc prolongation, whereas buprenorphine may not. This study has the advantage of confirming that QTc prolongation persists in patients in MMT but not in those in BMT over an extended period of time (i.e., 5 years). Buprenorphine might a better first-line opioid maintenance treatment for patients with heart disease because buprenorphine was not associated with QTc prolongation. Patients in BMT may not need to be screened routinely for QTc prolongation.

On-site Basic Health Screening and Brief Health Counseling of Chronic Medical Conditions for Veterans in Methadone Maintenance Treatment.

Background:To improve the delivery of health services for chronic medical conditions in our methadone clinic, we added an onsite health screening and brief health counseling to the treatment plans for patients receiving methadone maintenance treatment (MMT) at the Atlanta Veterans Affairs Medical Center. We then conducted a follow-up retrospective chart review to assess whether this intervention improved health outcome for those patients. Methods:We reviewed the charts of 102 patients who received treatment at Atlanta Veterans Affairs Medical Center methadone clinic between 2002 and 2008. We sought to determine whether our increased health education and screening intervention were associated with (1) improved drug addiction outcome (as measured by comparing percentage of opiate and cocaine positive drug screens from admission with most recent). (2) Basic health screening (as measured by the patient’s compliance with primary care physician appointments and current smoking status). (3) Management of co-occurring medical conditions (as measured by levels of low-density lipoprotein cholesterol, hemoglobin A1c, and systolic blood pressure). (4) Presence of QT interval corrected (QTc) prolongation (difference in QTc between baseline and most recent electrokardiogram). Results:Illicit drug use (opiate and cocaine) markedly decreased in patients overall. The effect was more robust for those successfully “retained” (n = 55, P < 0.0001) in treatment, compared with those who “dropped out” (n = 40, P = 0.05) of treatment. Compliance with primary care physician appointments was high (82% and 88% before and after the onsite intervention, respectively) for retained patients. Low-density lipoprotein cholesterol level was within normal range for all patients. A1c improved by 40% after the onsite intervention as reflected by the decreased percentage of patients with A1c >7% from before to after the intervention (90% vs 50%, P = 0.05). However, the prevalence of uncontrolled hypertension did not significantly improve after the onsite intervention (38% vs 28%, P = 0.34). As might be expected with MMT, the prevalence of QTc prolongation actually increased from 399 (±92) to 439 (±22) milliseconds after the onsite intervention (P = 0.003). Conclusions:Our retrospective study supports the previous literature that methadone maintenance therapy is effective in reducing illicit drug use. Although patients with history of heroin dependence and in MMT are at increased risk for chronic medical conditions, such as hepatitis C and diabetes, there are minimal federal guidelines for medical care, except than a physical examination on admission, and basic screening for some infectious diseases, eg, HIV and hepatitis C for those patients. Our study demonstrated the need for and potential benefit of enhancing the delivery of health promotion services for chronic medical conditions in methadone maintained patients. Improving management of hepatitis C, diabetes, hypertension, and other related conditions, in this high risk, difficult-to-treat, and underserved population may reduce their morbidity and premature mortality.

QTc interval prolongation for patients in methadone maintenance treatment: a five years follow-up study

Abstract Background: QTc prolongation for patients in methadone maintenance treatment (MMT) has been reported. In this study we wanted to identify the predictor factors for QTc prolongation >500 ms and other medical risk factors for mortality in this population. Methods: A retrospective chart review study with 55 patients who had previously been included in our performance improvement project and who were eligible to be reviewed. A linear regression model with one-sided p value was used for data analysis. Results: Over 5 years, 41% to 56% of patients had QTc > 450 and <500 ms and 4% to 10% of patients had at least one reading of QTc > 500 ms. This QTc prolongation from baseline showed statistical significance (p < 0.0001). Being diagnosed with congestive heart failure (CHF), elevated HgA1c level and recent cocaine use were significantly associated with QTc prolongation >500 ms. The model as a whole showed statistical significance (F = 3.50, p = 0.02). Being diagnosed with CHF and elevated HgA1c level was significantly associated with mortality. The model as a whole also showed statistical significance (F = 4.63, p = 0.01). Conclusions: This study confirms that methadone may be associated with QTc prolongation. It identified three risk factors for significant QTc prolongation for patients on MMT which are recent cocaine use, uncontrolled blood glucose and CHF. Two of these three risk facts (uncontrolled blood glucose and CHF) were associated with mortality in this cohort. Patients with these medical co-morbidities may benefit from EKG screening and aggressive treatment of the medical risk factors while taking MMT.