Long-term Treatment Retention Research Articles

Nine-year substance use treatment outcomes with buprenorphine for opioid use disorder in a federally qualified health center

BackgroundPrescribing medication for opioid use disorder (MOUD) in primary care helps meet treatment demand, but few studies examine long-term treatment retention among medically-underserved primary care patients. MethodsThis 9-year retrospective study assessed overall retention at 6 months, and yearly up to 9 years, among 1451 patients with at least 6 months of buprenorphine prescription data from a federally-qualified health center (FQHC). We also examined whether patients who had gaps in treatment (>14 days without medication) later returned to care. Associations with treatment retention over total time in care were assessed. ResultsOn average, patients received buprenorphine treatment for 2.26 years. Among patients who experienced gaps in treatment but returned to care within 90 days, 64% were still receiving buprenorphine at six months (n=930 of 1451), and 70% (n =118 of 169) at 9 years, with an average yearly interval retention of 69% (range: 58–74%). Patients were on MOUD treatment and not in a gap about 81% of the time, and averaged 1.0 gap per patient per year (SD: 1.09; range 0–7.87). The mean gap length over the treatment period was 33.16 days. Older age, higher percentages of negative opioid tests, negative cocaine tests, and positive buprenorphine tests, and having diabetes were associated with longer treatment retention. ConclusionsOpioid use disorder (OUD) can be treated successfully in primary care FQHCs. Treatment gaps are common and reflect the chronic relapsing nature of OUD.

10-year retention of a comprehensive treatment model of buprenorphine for opioid use disorder

Background There has been extensive research demonstrating the effectiveness of medications for opioid use disorder (MOUD) but limited investigation into its long-term retention rate. Objective Assess the long-term treatment retention of a buprenorphine-based MOUD clinic with additional stratifications by age and gender. Methods This retrospective study analyzed 10-years of data from a MOUD clinic in West Virginia that served 3,255 unique patients during the study period (2009-2019). Retention was measured by summation of total treatment days with a new episode of care defined as re-initiating buprenorphine treatment after 60+ consecutive days of nonattendance. Kaplan-Meier survival analysis, with the log-rank test, was used to compare retention by gender and age. Results The mean age was 38 (SD = 10.6) and 95% were non-Hispanic white. Irrespective of treatment episode, 56.8% of patients were retained ≥ 90 days, and the overall median time in treatment was 112 days. Considering only the first treatment episode, 48.4% of 3,255 patients were retained at least 90 days and the overall median was 77 days. Female patients had a ≥ 90 day retention rate of 52.2% for the first admission and 60.1% for multiple admissions, both significantly higher than those of male subjects (44.1% and 53.0%). Additionally, patients ≤ 24 years old had the lowest rate of treatment retention, while patients aged ≥ 35 had the highest. Conclusions This study adds to the limited data regarding long-term retention in MOUD. Our findings indicate gender and age were highly correlated with retention in MOUD treatment.

Long-term treatment retention of an emergency department initiated medication for opioid use disorder program

IntroductionMedication for Opioid Use Disorder (MOUD) has been shown to decrease mortality, reduce overdoses, and increase treatment retention for patients with opioid use disorder (OUD) and has become the state-of-the-art treatment strategy in the emergency department (ED). There is little evidence on long-term (6 and 12 month) treatment retention outcomes for patients enrolled in MOUD from the ED. MethodsA prospective observational study used a convenience sample of patients seen at one community hospital ED over 12 months. Patients >18 years with OUD were eligible for MOUD enrollment. After medical screening, patients were evaluated by the addiction care coordinator (ACC) who evaluated and counselled the patient and if eligible, directly connected them with an addiction medicine appointment. Once enrolled, the patient received treatment with buprenorphine in the ED. A chart review was completed for all enrollments during the first year of the program. Treatment retention was determined by review of the prescription drug monitoring program and defined as patients receiving regular suboxone prescriptions at 6 and 12 months after index ED visit date. ResultsFrom June 2018 - May 2019 the ACCs evaluated patients during 691 visits, screening 571 unique patients. Of the 571 unique patients screened, 279 (48.9%) were enrolled into the MOUD program. 210 (75.3%) attended their first addiction medicine appointment, 151 (54.1%) were engaged in treatment at 1 month, 120 (43.0%) at 3 months, 105 (37.6%) at 6 months, and 97 (34.8%) at 12 months post index ED visit. Self-pay insurance status was associated with a significantly decrease in the odds of long-term treatment retention. ConclusionOur ED-initiated MOUD program, in partnership with local addiction medicine services, produced high rates of long-term treatment retention.

Factors Associated with Long-Term Retention in Buprenorphine-Based Addiction Treatment Programs: a Systematic Review.

The average length of buprenorphine treatment for opioid use disorder is less than 6 months. We conducted a systematic review to determine what factors were associated with longer retention in buprenorphine treatment. We searched Medline, Embase, and Cochrane Database of Systematic Reviews in February 2018. Articles were restricted to randomized controlled trials on human subjects, written in English, which contained ≥ 24 weeks of objective data on retention in buprenorphine treatment. We assessed whether dose of buprenorphine, treatment setting, or co-administration of behavioral therapy was associated with retention rates. Over 14,000 articles were identified. Thirteen articles (describing 9 studies) met inclusion criteria. Measures of retention varied widely. Three studies compared doses of buprenorphine between 1 and 8 mg and showed significantly higher rates of retention with higher doses (p values < 0.01). All other studies utilized buprenorphine doses between 8 and 24 mg daily, without comparison. No study found a significant difference in retention between buprenorphine alone and buprenorphine plus behavioral therapy (p values > 0.05). Initiating buprenorphine while hospitalized or within criminal justice settings prior to outpatient treatment programs was significantly associated with retention in buprenorphine treatment (p values < 0.01 respectively). Setting of treatment initiation and a higher buprenorphine dose are associated with improved long-term treatment retention. More objective data on buprenorphine treatment programs are needed, including a standardized approach to defining retention in buprenorphine treatment programs. This review was registered with PROSPERO (#CRD42019120336) in March 2019.

Treatment retention in a specialized alcohol programme after an episode of alcoholic hepatitis: Impact on alcohol relapse

AimsAlcoholic hepatitis (AH) is a life-threatening complication of alcohol use disorder (AUD). Alcohol abstinence is the main predictor of the long-term prognosis of AH. It is unknown whether AUD treatment retention (TR) after an AH episode impacts alcohol relapse and mortality or what baseline factors influence TR. MethodsDesign: case-control study; Study population: hospitalized patients (1999–2012) with an episode of biopsy-proven AH were included (n = 120); Assessment: demographic and clinical data, the High-Risk Alcoholism Relapse (HRAR) scale, mortality and alcohol relapse were assessed through clinical records and telephone or personal interviews; Follow-up period: short-term and long-term TRs were assessed at 12 and 24 months, respectively. ResultsThe overall short-term and long-term TRs were 37% and 27.8%, respectively. The severity of liver disease at baseline predicted both short-term and long-term TR (OR 3.7 and 3.3, respectively), whereas HRAR >3 and a history of psychiatric disorders predicted long-term TR (OR 2.9 and 2.6, respectively). Moreover, HRAR >3 (OR 3.0) and previous treatment for AUD (OR 2.9) increased the risk of relapse in the short term. Importantly, receiving alcohol therapy in a centre different from the hospital where the patient was admitted was associated with increased risk of alcohol relapse over the long term (OR 5.4). ConclusionExperiencing an alcohol-related life-threatening complication is insufficient motivation to seek treatment for AUD. AUD treatment after an episode of AH is suboptimal, with a low TR rate, high risk of alcohol relapse and poor impact of treatment on alcohol relapse.

Patterns and predictors of long-term retention of inflammatory bowel or rheumatoid disease patients on innovator infliximab: an analysis of a Canadian prescriptions claims database.

BackgroundLong-term effectiveness is an important factor when considering treatment decisions.ObjectiveTo determine the long-term retention patterns of Canadian inflammatory bowel disease (IBD) and rheumatologic disease (RD) patients, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with innovator infliximab (IFX) and to assess the impact of year-over-year cumulative IFX exposure on retention in both patient populations.Patients and methodsThis analysis used a Canadian longitudinal prescription claims database to measure retention on IFX over a period of 5 years. Twelve-month unadjusted odds ratios of retention by time on IFX were calculated for the overall cohort, and within-group comparisons evaluated differences according to age, sex, region, insurance coverage, use of concomitant immunosuppressant therapy, indication (RD cohort only), and previous biologic experience. Between-group analyses compared unadjusted 5-year retention among the same variables. Variables that were independently associated with longer retention on IFX were identified using multivariable regression.ResultsSeven thousand eight hundred and six IBD patients and 2,935 RD patients on stable treatment with IFX were included in the analysis. Sixty-nine percent of IBD patients and 66% of RD patients were retained on IFX after 1 year and 33% and 29%, respectively, were retained after 5 years. Moreover, the probability of being retained on IFX significantly increased with cumulative time on IFX. Independent predictors of 5-year retention included sex, region, and type of insurance coverage among IBD patients and region, type of insurance, prior biologic therapy, and specific indication among RD patients. Patients with IBD were 17% more likely to be retained on IFX over 5 years compared to patients with RD.ConclusionReal-world Canadian IBD and RD patients on IFX have good overall long-term treatment retention. Previous duration of IFX treatment predicts better future retention, and this knowledge could help inform treatment decisions when patients have been stable on IFX treatment for varying periods of time.

Public sector low threshold office-based buprenorphine treatment: outcomes at year 7

BackgroundBuprenorphine maintenance for opioid dependence remains of limited availability among underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care treatment models including the use of unobserved, “home,” buprenorphine induction may simplify initiation of care and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently among large, naturalistic cohorts treated in low threshold safety net primary care settings.MethodsThis prospective clinical registry cohort design estimated rates of induction-related adverse events, treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic retention, buprenorphine dosages, and urine sample results.ResultsOf the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%; serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a median 38 weeks (range 0–320) for inductions, compared to 110 (0–354) weeks for transfers and 57 for the entire clinic population. Older age, later years of first clinic visit (vs. 2006–2007), and baseline heroin abstinence were associated with increased treatment retention overall.ConclusionsUnobserved “home” buprenorphine induction in a public sector primary care setting appeared a feasible and safe clinical practice. Post-induction treatment retention of a median 38 weeks was in line with previous naturalistic studies of real-world office-based opioid treatment. Low threshold treatment protocols, as compared to national guidelines, may compliment recently increased prescriber patient limits and expand access to buprenorphine among public sector opioid use disorder patients.

Long-term retention in Office Based Opioid Treatment with buprenorphine

BackgroundGuidelines recommend long-term treatment for opioid use disorder with buprenorphine; however, little is known about patients in long-term treatment. The aim of this study is to examine the prevalence and patient characteristics of long-term treatment retention (≥1year) in an Office Based Opioid Treatment (OBOT) program with buprenorphine. MethodsThis is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014 in a large urban safety-net primary care OBOT program. The primary outcome was retention in OBOT for at least one continuous year. Potential predictors included age, race, psychiatric diagnoses, hepatitis C, employment, prior buprenorphine, ever heroin use, current cocaine, benzodiazepine and alcohol use on enrollment. Factors associated with ≥1year OBOT retention were identified using generalized estimating equation logistic regression models. Patients who re-enrolled in the program contributed repeated observations. ResultsThere were 1605 OBOT treatment periods among 1237 patients in this study. Almost half, 45% (717/1605), of all treatment periods were ≥1year and a majority, 53.7% (664/1237), of patients had at least one ≥1year period. In adjusted analyses, female gender (Adjusted Odds Ratio [AOR] 1.55, 95% CI [1.20, 2.00]) psychiatric diagnosis (AOR 1.75 [1.35, 2.27]) and age (AOR 1.19 per 10year increase [1.05, 1.34]) were associated with greater odds of ≥1year retention. Unemployment (AOR 0.72 [0.56, 0.92]), Hepatitis C (AOR 0.59 [0.45, 0.76]), black race/ethnicity (AOR 0.53 [0.36, 0.78]) and Hispanic race/ethnicity (AOR 0.66 [0.48, 0.92]) were associated with lower odds of ≥1year retention. ConclusionsOver half of patients who presented to Office Based Opioid Treatment with buprenorphine were ultimately successfully retained for ≥1year. However, significant disparities in one-year treatment retention were observed, including poorer retention for patients who were younger, black, Hispanic, unemployed, or with hepatitis C.

Opioid use and dropout in patients receiving oral naltrexone with or without single administration of injection naltrexone

BackgroundAdherence to oral naltrexone has been poor and can be improved somewhat with behavioral therapy. We compared behavioral naltrexone therapy (BNT) to compliance enhancement (CE) and tested efficacy of single-dose injection naltrexone (XR-NTX; 384mg) with behavioral therapies at further improving adherence to oral naltrexone. MethodsA 24-week, randomized, placebo-controlled trial (n=125) compared four treatment conditions following inpatient detoxification and oral naltrexone induction: (1) BNT+XR-NTX; (2) BNT+placebo injection; (3) CE+XR-NTX; and (4) CE+placebo injection. All participants were maintained on oral naltrexone throughout the trial. Primary outcome was retention in treatment. ResultsOf 89 randomized participants, 78.7% (70/89) completed 4 weeks, 58.2% (54/89) completed 8 weeks, 47.2% (42/89) completed 12 weeks, and 25.8% (23/89) completed 24 weeks. A Cox proportional hazards regression modeled time to dropout as a function of treatment condition, baseline opioid dependence severity (bags per day of heroin use), and their interaction. Interaction of conditions by baseline severity was significant (X32=9.19, p=0.027). For low-severity patients (≤6 bags/day), retention was highest in the BNT−XR-NTX group (60% at 6 months), as hypothesized. For high-severity (>6 bags/day) patients, BNT−XR-NTX did not perform as well, due to high early attrition. ConclusionFor low-severity heroin users, single-dose XR-NTX improved long-term treatment retention when combined with behavioral therapy. In higher-severity opioid-dependent patients, XR-NTX was less helpful, perhaps because, combined with oral naltrexone, it produced higher blood levels and more withdrawal discomfort. When cost considerations recommend oral naltrexone following XR-NTX, the latter should be phased in slowly.

The time course of gastric methotrexate intolerance in patients with rheumatoid arthritis and psoriatic arthritis

Objectives This study aimed to evaluate the incidence and the time course of methotrexate (MTX)-associated gastric intolerance in patients with rheumatoid arthritis and psoriatic arthritis.Methods Four hundred twenty subjects undergoing MTX treatment for rheumatoid arthritis (n = 346) and psoriatic arthritis (n = 74) were retrospectively assessed. The incidence and time course of gastric MTX intolerance resulting in treatment discontinuation were investigated. In addition, the relations between gastric intolerance and patient characteristics, including gender, age, diagnosis, and rheumatoid factor (RF) positivity, were examined.Results Overall, oral MTX discontinuation rate due to gastric intolerance was 28.6 %. The time to discontinuation for oral MTX was 8.1 ± 11.5 months on average, with more than half of the discontinuations occurring within the first three months of treatment. Discontinuation was not associated with gender, age, diagnosis, or RF positivity. More than half of the patients that switched to a parenteral treatment regimen (52.6 %, 20/38) could tolerate the agent.Conclusions Gastric MTX intolerance usually develops within the first year of treatment and presents a major obstacle to long-term treatment retention in patients with rheumatologic disease. However, parenteral MTX appears to be a good alternative for patients intolerant of oral MTX.

The time course of gastric methotrexate intolerance in patients with rheumatoid arthritis and psoriatic arthritis

This study aimed to evaluate the incidence and the time course of methotrexate (MTX)-associated gastric intolerance in patients with rheumatoid arthritis and psoriatic arthritis. Four hundred twenty subjects undergoing MTX treatment for rheumatoid arthritis (n = 346) and psoriatic arthritis (n = 74) were retrospectively assessed. The incidence and time course of gastric MTX intolerance resulting in treatment discontinuation were investigated. In addition, the relations between gastric intolerance and patient characteristics, including gender, age, diagnosis, and rheumatoid factor (RF) positivity, were examined. Overall, oral MTX discontinuation rate due to gastric intolerance was 28.6 %. The time to discontinuation for oral MTX was 8.1 ± 11.5 months on average, with more than half of the discontinuations occurring within the first three months of treatment. Discontinuation was not associated with gender, age, diagnosis, or RF positivity. More than half of the patients that switched to a parenteral treatment regimen (52.6 %, 20/38) could tolerate the agent. Gastric MTX intolerance usually develops within the first year of treatment and presents a major obstacle to long-term treatment retention in patients with rheumatologic disease. However, parenteral MTX appears to be a good alternative for patients intolerant of oral MTX.

Oxcarbazepine long-term treatment retention in patients switched over from carbamazepine

We evaluated the long-term outcome of oxcarbazepine (OXC) monotherapy in a population of patients switched over from carbamazepine (CBZ) monotherapy. Subjects of the study were recruited among patients who had successfully completed the PRIMO study, a recent multicentre Italian study that assessed the therapeutic equivalence of immediate (overnight) and more progressive switching from CBZ to OXC monotherapy in patients with partial seizures unsatisfactorily maintained on CBZ monotherapy due to poor tolerability or scant clinical efficacy. Treatment retention rate was chosen as a composite parameter for both efficacy and tolerance of OXC. Twelve months after having completed the PRIMO study, 91 of 105 patients (87%) were still taking OXC, 80 of them (76%) as monotherapy. Mean OXC dose was 1250+/-459 mg/day. Eighty-four out of 105 patients (80%) rated OXC tolerability as "good" or "very good". The mean ratio of the last dose of OXC to the last dose of CBZ increased from 1.54 (end of PRIMO study) to 1.69 (end of follow-up). The large majority of a population of patients who were successfully switched from CBZ monotherapy to OXC monotherapy maintained OXC treatment for at least a further 12 months. The 1.5 OXC/CBZ ratio appears to be close to the optimal for the switch from CBZ to OXC, at least in patients treated with CBZ monotherapy.

The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review

To examine the clinical effectiveness and cost-effectiveness of newer antiepileptic drugs (AEDs) for epilepsy in children: gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate and vigabatrin. Electronic databases. Drug company submissions. For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria. Data extraction and quality assessment were also undertaken. A decision-analytic model was constructed to estimate the cost-effectiveness of the newer agents in children with partial seizures, the only condition where there were sufficient trial data to inform a model. The quality of the randomised controlled trial (RCT) data was generally poor. For each of the epilepsy subtypes considered in RCTs identified for this review (partial epilepsy with or without secondary generalisation, Lennox-Gastaut syndrome, infantile spasms, absence epilepsy and benign epilepsy with centrotemporal spikes), there is some evidence from placebo-controlled trials that the newer agents tested are of some value in the treatment of these conditions. Where active controls have been used, the limited evidence available does not indicate a difference in effectiveness between newer and older drugs. The data are not sufficient to inform a prescribing strategy for any of the newer agents in any of these conditions. In particular, there is no clinical evidence to suggest that the newer agents should be considered as a first-choice treatment in any form of epilepsy in children. Annual drug costs of the newer agents ranges from around 400 pound to 1200 pound, depending on age and concomitant medications. An AED that is ineffective or has intolerable side-effects will only be used for a short period of time, and many patients achieving seizure freedom will successfully withdraw from drug treatment without relapsing. The results of the decision-analytic model do not suggest that the use of the newer agents in any of the scenarios considered is clearly cost-effective but, similarly, do not indicate that they are clearly not cost-effective. The prognosis for children diagnosed with epilepsy is generally good, with a large proportion responding well to the first treatment given. A substantial proportion, however, will not respond well to treatment, and for these patients the clinical goal is to find an optimal balance between the benefits and side-effects of any treatment given. For the newly, or recently, diagnosed population, the key question for the newer drugs is how soon they should be tried. The cost-effectiveness of using these agents early, in place of one of the older agents, will depend on the effectiveness and tolerability of these agents compared with the older agents; the evidence from the available trial data so far suggests that the newer agents are no more effective but may be somewhat better tolerated than the older agents, and so the cost-effectiveness for early use will depend on the trade-off between effectiveness and tolerability, both in terms of overall (long-term) treatment retention and overall utility associated with effects on seizure rate and side-effects. There are insufficient data available to estimate accurately the nature of this trade off either in terms of long-term treatment retention or utility. Better information is required from RCTs before any rational evidence-based prescribing strategy could be developed. Ideally, RCTs should be conducted from a 'public health' perspective, making relevant comparisons and incorporating outcomes of interest to clinicians and patients, with sufficiently long-term follow-up to determine reliably the clinical utility of different treatments, particularly with respect to treatment retention and the balance between effectiveness and tolerability. RCTs should mirror clinical practice with respect to diagnosis, focusing on defined syndromes or, where no syndrome is identified, on groups defined by specific seizure type(s) and aetiology. Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options and outcomes. Diagnosis-specific decision-analytic models are required; further research may be required to inform parameter values adequately with respect to epidemiology and clinical practice.

Long-Term Treatment Retention with Topiramate

Long-Term Treatment Retention with Topiramate

Oral methadone self-administration: effects of dose and alternative reinforcers.

We examined the efficacy of oral methadone as a reinforcer by offering methadone maintenance patients the chance to self-administer extra doses of methadone occasionally in addition to their regular dose. Seven maintenance patients received twice-weekly choices between methadone doses or money. Doses were 0, 1, 5, 10, 25, or 50 mg methadone; the alternative money option was $1 or $5. Extra methadone doses were reliably self-administered by maintenance patients, and percent of dose choices rose as the size of the dose offered increased. Thus extra methadone doses functioned as reinforcers in this situation. Further, across the entire dose range, more dose choices were selected when $1 was offered than when $5 was offered as an alternative. Thus methadone self-administration was influenced by the alternative reinforcers available for drug refusal. Neither reports of subjective withdrawal symptoms nor reduction of symptoms after extra methadone predicted methadone self-administration, but dose selections were more likely when urinalysis results indicated recent illicit opiate use. The reinforcing effects of oral methadone in methadone-tolerant patients may be an important factor in the popularity of this treatment among drug abusers and in the long-term treatment retention generally observed during methadone maintenance.