Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth

Background

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment.

Methods

Opioid dependent adolescents and young adults (n = 152), aged 15–21, were randomized to 12 weeks (BUP, n = 74) or 2 weeks of detoxification (DETOX, n = 78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression.

Results

In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition.

Conclusions

Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.     

Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision

Aims

Several studies have demonstrated the importance of agonist therapies such as methadone and buprenorphine for preventing relapse for individuals being released from jail or prison to the community. No studies have examined the impact of methadone for increasing the completion of community supervision requirements and preventing opioid relapse for individuals under community corrections supervision. This observational study compared the community corrections completion rate and opioid relapse rate of individuals receiving methadone maintenance therapy (MMT) to individuals who did not.

Methods

Of the 2931 individuals enrolled under criminal justice supervision in the community, Treatment Accountability for Safer Communities (TASC), and who met criteria for opioid dependence, 329 (11%) individuals reported receiving MMT in the community.

Results

The majority of participants were White (79.8%) and male (63.5%), with a mean age of 31.33 years (SD = 9.18), and were under supervision for 10.4 months (SD = 9.1). MMT participants were less likely to fail out of supervision compared to individuals not in MMT (39.0% vs. 52.9%, p < 0.001), and had a lower rate of relapse (32.9%) and longer time to relapse (average days = 89.7, SD = 158.9) compared to the relapse rate (55.9%) and time to relapse (average days = 60.5, SD = 117.9) of those not on MMT.

Conclusions

While the observational nature of this study prevents causal inferences, these results suggest that utilization of MMT in community corrections may increase the likelihood of completing supervision requirements and delay time to opioid relapse. Providing agonist therapies to opioid dependent individuals under supervision appears to be a critical strategy in this important population.     

Primary care patient characteristics associated with completion of 6-month buprenorphine treatment

Background

Opioid addiction is prevalent in the United States. Detoxification followed by behavioral counseling (abstinence-only approach) leads to relapse to opioids in most patients. An alternative approach is substitution therapy with the partial opioid receptor agonist buprenorphine, which is used for opioid maintenance in the primary care setting. This study investigated the patient characteristics associated with completion of 6-month buprenorphine/naloxone treatment in an ambulatory primary care office.

Methods

A retrospective chart review of 356 patients who received buprenorphine for treatment of opioid addiction was conducted. Patient characteristics were compared among completers and non-completers of 6-month buprenorphine treatment.

Results

Of the 356 patients, 127 (35.7%) completed 6-month buprenorphine treatment. Completion of treatment was associated with counseling attendance and having had a past injury.

Conclusions

Future research needs to investigate the factors associated with counseling that influenced this improved outcome. Patients with a past injury might suffer from chronic pain, suggesting that buprenorphine might produce analgesia in addition to improving addiction outcome in these patients, rendering them more likely to complete 6-month buprenorphine treatment. Further research is required to test this hypothesis. Combination of behavioral and medical treatment needs to be investigated for primary care patients with opioid addiction and chronic pain.     

The effect of telephonic patient support on treatment for opioid dependence: outcomes at one year follow-up

Objective

The present study examined the impact of a telephonic patient support program known as HereToHelp™ (HTH) on compliance and treatment outcomes among opioid dependent (OD) patients new to buprenorphine treatment (BUP).

Method

A total of 1426 OD patients new to BUP were randomized to receive BUP alone (standard care) or BUP plus the HTH patient support program. All patients completed the Addiction Severity Index (ASI) at the time of enrollment, and at 12 months post-enrollment.

Results

Subjects randomized to the HTH support program who accepted at least 3 care coach intervention calls were more compliant with BUP than the standard care group at month 12 (64.4% vs. 56.1%, χ² = 5.09, p < .025). Compared to patients who were non-compliant with BUP, compliant patients reported significantly lower scores on all 7 of the ASI composite scores, indicating lower severity on addiction-related problems.

Conclusions

The HTH intervention seemed to improve patient treatment outcomes indirectly by improving compliance with BUP. Supplementing BUP with a structured, telephonic compliance-enhancement program is an effective way to improve compliance with medication which then improves patient outcomes.     

Differential effects of methadone and buprenorphine on the response of D2/D3 dopamine receptors in adolescent mice

Background

There is a lack of studies that examine the effects of opioid maintenance drugs on the developing adolescent brain, limiting the ability of physicians to conduct a science-based risk assessment on the appropriateness of these treatments for that age group. Our recent observations indicate higher potential risks in repeated exposure to morphine during adolescence, specifically to the D2/D3 dopamine receptors’ signaling. Disturbances in dopaminergic signaling could have broader implications for long-term mental health. Thus, this study examined whether buprenorphine and methadone differentially alter the responses of the D2/D3 dopamine receptors in adolescents.

Methods

Adolescent mice were orally administered buprenorphine (0.1–0.4 mg/kg), methadone (25–100 mg/kg), or saline once daily for 6 days. Two hours or three days later, the mice were tested for their locomotor response to 10 mg/kg quinpirole, a D2/D3 dopamine receptor agonist.

Results

Buprenorphine-treated adolescent mice did not significantly differ from control drug-naïve animals in their response to quinpirole. However, an enhanced response was observed in methadone-treated adolescent animals. This enhanced locomotion was significantly higher two hours following the final dose of methadone, as compared to three days afterwards.

Conclusions

This study suggests that exposure to various opioids carries differential probabilities of altering the highly sensitive neurochemistry of adolescent brains. Methadone exposure disturbs the D2-like receptor's response, indicating a potential risk in administering methadone to adolescents (either for the treatment of opioid dependency/abuse or for pain management). In contrast, buprenorphine appears to have a significantly lower effect on the behavioral sensitivity of D2/D3 dopamine receptors in adolescents.     

Non-opioid induction of morphine-6-glucuronide synthesis is elicited by prolonged exposure of rat hepatocytes to heroin

Background

Liver metabolism of morphine leads to the formation of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), the latter possessing strong opioid activity that however differs from that of the parent compound. In previous studies conducted in rats we have shown that repeated in vivo exposure to phenanthrene class of mu opioid receptor (MOR) agonists or antagonists (heroin, morphine, and naltrexone), but not to non-phenanthrene class of MOR agonist methadone, affects morphine glucuronidation by liver microsomes.

Methods

In the present study, we measured the in vitro formation of M3G and M6G by rat hepatocytes incubated for 120 min with morphine (0.1–1.0 mM) after 72 h pre-incubation with one of the following MOR agonists: heroin (3.3 or 6.6 μM), morphine (7.8 μM), or methadone (12 μM). The MOR antagonist naltrexone (10 or 25 μM) was also tested, alone or in combination with heroin. The amount of M3G and M6G synthesized was then measured by HPLC method.

Results

Heroin inhibited M3G synthesis and induced the formation of M6G, which under basal conditions is not synthesized in rats. Heroin effects were not blocked by naltrexone. Morphine, but not methadone, produced effects similar to those of heroin but more modest in intensity. Pre-incubation with naltrexone alone slightly increased M3G synthesis, but had no effect on M6G formation.

Conclusions

These results are in agreement with those of previous ex vivo studies and indicate that exposure to heroin or, to a lesser extent, morphine, can affect morphine glucuronidation via direct non-opioid actions on the hepatocytes.     

Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline

Objective

The hospital can be an important opportunity for smoking cessation interventions. This is the first randomized, double-blinded, placebo-controlled pilot trial utilizing varenicline and post-discharge, in-person behavioral treatment for hospitalized smokers.

Method

Seventy-nine smokers admitted to a university-based hospital with various diagnoses were enrolled from 2007 to 2009. The primary outcome was biochemically confirmed abstinence at 24 weeks following discharge. Secondary outcomes included withdrawal symptoms, motivation, utilization of treatment, and medical events.

Results

Overall abstinence at 24 weeks was 27% with no difference between varenicline and placebo treatment groups (23% vs. 31%). There were no significant differences in motivation to stop smoking or withdrawal symptoms. Over 40% of all subjects utilized post-discharge behavioral treatment with significantly higher abstinence rates compared with those who did not (53.1% vs. 8.5%, p < 0.01). Overall adverse events were similar in both treatment groups with the only significant difference being more nausea in the varenicline group (25% vs. 5%; p < 0.01). Twenty-three subjects were re-hospitalized with no significant differences between treatment groups (13 varenicline vs. 10 placebo).

Conclusion

This pilot trial of varenicline in hospitalized smokers demonstrated feasibility of implementation, produced some hypothesis-generating findings, and suggested the potential benefit of face-to-face treatment following discharge.     

A “community-friendly” version of integrated group therapy for patients with bipolar disorder and substance dependence: A randomized controlled trial

Background

Integrated group therapy, a new treatment for patients with bipolar disorder and substance use disorder, has previously been found to be efficacious in reducing substance use, but its length (20 sessions) and need for highly trained therapists may limit its adoption in substance use disorder community treatment programs. This paper compares a briefer (12 session) version of integrated group therapy, led by substance use disorder counselors without previous cognitive-behavioral training or bipolar disorder experience, to group drug counseling.

Methods

Sixty-one patients with bipolar disorder and substance dependence, taking mood stabilizers, were randomized to 12 sessions of integrated group therapy (n = 31) or group drug counseling (n = 30).

Results

Analyses of primary outcomes showed trends favoring integrated group therapy, with greater reduction in substance use during follow-up and a greater decline in risk of mood episodes during treatment. Secondary analyses favored integrated group therapy, with a significantly greater likelihood of achieving total abstinence, a significantly shorter time to the first abstinent month, and a significantly greater likelihood of achieving a “good clinical outcome” (a composite measure encompassing both substance use and mood simultaneously).

Conclusions

A shortened version of integrated group therapy can be delivered successfully by substance use disorder counselors, with better overall outcomes than those achieved with group drug counseling.     

The construct and measurement equivalence of cocaine and opioid dependences: A National Drug Abuse Treatment Clinical Trials Network (CTN) study

Introduction

Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups.

Methods

Item response theory (IRT) and multiple indicators–multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N = 383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist.

Results

IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. “Withdrawal” identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence.

Conclusions

Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.     

A preliminary study of the neural effects of behavioral therapy for substance use disorders

Background

The mechanisms by which behavioral therapies for substance use disorders (SUDs) exert their effects and the components of treatment that contribute most to substance use outcome remain unclear. Disruptions to aspects of impulse control and attention have been hypothesized to contribute to the development and maintenance of addiction; moreover, alterations in these processes may underlie responses to treatment.

Methods

Individuals participating in a randomized clinical trial evaluating computer-assisted cognitive behavioral therapy (CBT) for substance abuse participated in fMRI Stroop before and after treatment. A non-substance-using comparison group performed the same task under test–retest conditions.

Results

The patient group demonstrated decreased Stroop-related BOLD signal in regions including the anterior cingulate, inferior frontal gyrus and midbrain at post-treatment relative to pre-treatment, and displayed a greater decrease in the subthalamic nucleus and surrounding regions compared to healthy controls following test–retest.

Conclusions

Behavioral therapies may be associated with reduction in substance use and effects on neural systems involved in cognitive control, impulsivity, motivation and attention.     

Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: a comparison of fetal neurobehaviors and infant outcomes

Background

It is suspected that there is a continuum of impairment among prenatally drug-exposed infants, such that opioid and/or poly-drug exposure confers the highest risk for adverse neonatal outcomes than other classes of substances or single substance exposures. Suitable control groups are difficult to identify. This study compared fetal neurobehavioral development and infant outcomes in offspring of three groups of pregnant women in drug treatment. Exposure groups include: Methadone + other illicit substances (MM + Poly) and two groups currently abstinent for poly drug exposures: Methadone only (MM/A) and Non-Methadone (NM/A).

Methods

Forty-nine women (19 MM + Poly, 18 MM/A, and 12 NM/A) underwent fetal monitoring at 36 weeks gestation at peak and trough levels of methadone (MM + Poly; MM/A) or at comparable morning and afternoon times (NM/A). Fetal heart rate (FHR), heart rate variability (FHRV) and motor activity (FM) data were collected. Infant measures included birth outcomes and Neonatal Abstinence Syndrome (NAS) assessment.

Results

As compared to the NM/A group, cardiac measures were decreased in methadone-exposed fetuses at peak levels. FHR was significantly more suppressed in the MM + Poly group. FM was significantly lower in the MM/A vs. the NM/A group at both peak and trough, indicative of more persistent exposure effects. The MM + Poly group delivered 1 week earlier and required NAS pharmacological treatment twice as often as the MM/A group.

Conclusions

Results support the notion that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlights the need for intensified treatment for methadone-maintained women who abuse other substances.     

Methadone and buprenorphine-naloxone are effective in reducing illicit buprenorphine and other opioid use,and reducing HIV risk behavior—Outcomes of a randomized trial

Aims

Determine the extent to which buprenorphine injectors continue treatment with buprenorphine-naloxone or methadone, and the impact of these treatments on substance use and HIV risk in the Republic of Georgia.

Methods

Randomized controlled 12-week trial of daily-observed methadone or buprenorphine-naloxone followed by a dose taper, referral to ongoing treatment, and follow-up at week 20 at the Uranti Clinic in Tbilisi, Republic of Georgia. Eighty consenting treatment-seeking individuals (40/group) aged 25 and above who met ICD-10 criteria for opioid dependence with physiologic features and reported injecting buprenorphine 10 or more times in the past 30 days. Opioid use according to urine tests and self-reports, treatment retention, and HIV risk behavior as determined by the Risk Assessment Battery.

Results

Mean age of participants was 33.7 (SD5.7), 4 were female, mean history of opioid injection use was 5.8 years (SD4.6), none were HIV+ at intake or at the 12-week assessment and 73.4% were HCV+. Sixty-eight participants (85%) completed the 12-week medication phase (33 from methadone and 35 from buprenorphine/naloxone group); 37 (46%) were in treatment at the 20-week follow-up (21 from methadone and 16 from the buprenorphine/naloxone group). In both study arms, treatment resulted in a marked reduction in unprescribed buprenorphine, other opioid use, and HIV injecting risk behavior with no clinically significant differences between the two treatment arms.

Conclusions

Daily observed methadone or buprenorphine-naloxone are effective treatments for non-medical buprenorphine and other opioid use in the Republic of Georgia and likely to be useful for preventing HIV infection.     

Quality of life under maintenance treatment with heroin versus methadone in patients with opioid dependence

Background

There is increasing evidence that health-related quality of life (HRQOL) is associated with a successful treatment and better outcome in opioid addiction. The aim of the present study was the longitudinal investigation of HRQOL in patients with severe opioid dependence, who were randomly assigned to four groups of medical and psychosocial treatment: heroin (diacetylmorphine) versus methadone and case management (CM) versus psychoeducation (PSE) respectively.

Methods

HRQOL (MSQoL) and physical health (OTI) were investigated in 938 subjects, who participated in the German multi-centre study examining the effects of heroin-assisted treatment in patients with severe opioid dependence. Data for the present analysis were taken from baseline and 12-month follow up.

Results

Under both forms of maintenance and psychosocial treatment HRQOL improved significantly during the observation period. HRQOL improvement under maintenance with heroin exceeded improvement under methadone, especially with regard to subjective physical health. HRQOL improvement was significantly associated with better expert-rated physical health. Further analyses showed significant better improvement of HRQOL in subjects treated with PSE compared with CM.

Conclusions

The advantage of heroin with regard to the improvement of HRQOL may be partially explained by a better improvement of physical health under maintenance with heroin compared with methadone, which highlights the importance of a comprehensive model of health care for patients with severe opioid dependence. Future studies need to investigate the benefits of PSE for patients in maintenance therapy.     

Receipt of opioid agonist treatment in the Veterans Health Administration: facility and patient factors

Background

Opioid agonist treatment (OAT)—through licensed clinic settings (C-OAT) using methadone or buprenorphine or office-based settings with buprenorphine (O-OAT)—is an evidence-based treatment for opioid dependence. Because of limited availability of on-site C-OAT (n = 28 of 128 facilities) in the Veterans Health Administration (VHA), O-OAT use has been encouraged. This study examined OAT utilization across VHA facilities and the patient and facility factors related to variability in utilization.

Method

We examined 12 months of VHA administrative data (fiscal year [FY] 2008, October 2007 through September 2008) for evidence of OAT utilization and substance use disorder program data from an annual VHA survey. Variability in OAT utilization across facilities and patient and facility factors related to OAT utilization were examined using mixed-effects, logistic regression models.

Results

Among 128 VHA facilities, 35,240 patients were diagnosed with an opioid use disorder. Of those, 27.3% received OAT: 22.2% received C-OAT and 5.1% received O-OAT with buprenorphine. Substantial facility-level variability in proportions of patients treated with OAT was found, ranging from 0% to 66% with 44% of facilities treating <5%. Significant patient-level predictors of OAT receipt included being male, age ≥56, and without another mental health diagnosis. Significant facility-level predictors included offering any OAT services (C-OAT or O-OAT) and specialty substance abuse treatment services on weekends.

Conclusion

In FY2008, prior to the VHA national mandate of access to buprenorphine OAT, substantial variation in the use of OAT existed, partially explained by patient- and facility-level factors. Implementation efforts should focus on increasing access to this evidence-based treatment, especially in facilities at the low end of the distribution.     

Adolescents' self-reported reasons for using nicotine replacement therapy products: a population-based study

Background

Available research provides evidence that adolescents use nicotine replacement therapy (NRT) products. Yet, little is known about reasons and motives behind their use. The present study examined the reasons for NRT use among 14–18-year-old Finnish adolescents.

Method

A national Adolescent Health and Lifestyle Survey was conducted in Finland in 2009 (N = 4834, response rate 55%). Main measures were prevalence of NRT use, self-reported reasons for using NRT and smoking status.

Results

Overall, 10% had used NRT. Boys used NRT more often than girls (11.5% versus 8.7%, p < .001). The three most commonly reported reasons were ‘just try’ (56%), ‘to quit’ (33%) and ‘smoking not possible’ (24%). “Just try” was the most common reason given by non-smokers/experimental smokers whereas daily/occasional smokers used NRT mainly for quitting purposes and when smoking was impossible.

Conclusions

These findings suggest that when planning treatment plans for adolescent smokers, health care personnel should pay particular attention to adolescents' primary reasons and motives for using NRT before suggesting its use.     

Factors associated with dropout among patients in opioid maintenance treatment (OMT) and predictors of re-entry. A national registry-based study

Background

Retention in treatment is often highlighted as one of the key indicators of success in opioid maintenance treatment (OMT).

Aims

To identify factors associated with long-term retention in opioid maintenance treatment and to analyse predictors of subsequent treatment episodes.

Methods

Treatment retention and re-entry were examined for a national cohort of patients admitted to OMT in Norway in the period 1997–2003. Multivariate Cox regression models were used to investigate factors associated with treatment dropout 18 months after treatment entry.

Results

The 18 month retention rate among patients admitted to OMT in Norway (n = 2431) was 65.8% (n = 1599). Dropout from OMT within 18 months was associated with younger age (HR 0.97 [0.96–0.98]), high levels of general pre-treatment criminal offences (HR 1.66 [1.32–2.09]) and having drug-related offences during the 30 days prior to dropout (HR 1.80 [1.36–2.38]). Of the patients who dropped out (n = 832), 42.7% (n = 355) were re-engaged in subsequent treatment episodes. Pre-treatment criminal offences were associated with increased odds for treatment re-entry, whereas being younger and having drug-related offences during the first OMT episode were associated with lower odds for re-engagement in OMT. Gender was not associated with treatment dropout and re-entry.

Conclusion

High levels of pre-treatment criminal offences and drug offences during the 30 days prior to dropout were associated with treatment dropout. Efforts to increase support services to these patients may contribute to higher rates of retention in OMT.