Higher Methadone Research Articles

The "Micro"cosm: Magnifying the Nuance of Low Dose Buprenorphine Inductions.

Now that the X-wavier is a thing of the past, patients with Opioid Use Disorder (OUD) who previously lacked access to buprenorphine may have access to lower barrier care and may be looking to make the transition from either methadone or illicit fentanyl to buprenorphine. This can be quite challenging and both fentanyl and methadone are hihghly potent drugs and can result in a difficult transtition to buprenorphine. A transition from high potency opioids to buprenorphine is challenging and can cause discomfort or withdrawal in patients. Procedures/data/observations: Patients tend to have a difficult time when undergoing a transition from significant fentanyl use (> 1 bundle/day) or high dose methadone to buprenorphine. Over the last year, we've supported this transition for our hospitalized patients and have learned some tips and tricks to ease the transitions. Through our work we've come up with a strategy to transition patients that includes utilizing full mu agonists while initiating a low dose buprenorphine induction. We have developed an informal protocol for this transition that takes advantage of the flexibility of low dose buprenorphine induction strategies and includes the use of non-opioid adjuvant medications to control symptoms of discomfort and withdrawal. A transition from the use of significant fentanyl or high dose methadone to buprenorphine is possible and can take place over a matter of a few days. Such a transition requires careful attention to patient symptoms, availability of as needed short acting opioids, and the judicious use of non-opioid adjuvants.

Biochemical differences between high and low dose methadone clients on stable maintenance therapy

The methadone dose required to prevent withdrawal symptoms in chronic methadone users varies dramatically from 5 to 300 mg/day, which could be attributed to a number of biochemical factors, including human µ-opioid receptor (hMOR) density, down-stream desensitization, concurrent drug use or P-glycoprotein (P-gp) expression, or other, possibly genetic factors. Here we describe some biochemical changes of patients taking higher versus lower doses in chronic methadone maintenance therapy (MMT). hMOR density was measured in leukocytes from methadone-maintained patients receiving lower dose (<100 mg/day) or higher dose (≥100 mg/day) and naive subjects by flow cytometry. Desensitization of receptor signaling was examined by measuring in vivo and attenuated cyclic AMP (cAMP) levels in response to increasing methadone concentrations. P-gp expression and the presence of other drugs were measured using validated methods.

Exploring factors jointly associated with recurrent relapse and dropout of methadone maintenance treatment clients in Guangdong, China: A retrospective cohort study

BackgroundClients receiving methadone maintenance treatment (MMT) may experience multiple relapses, which may lead to dropout. However, previous studies mostly only explored the influencing factors of relapse or dropout separately. In this study, we investigated the influencing factors jointly associated with both recurrent relapse and dropout. MethodsThis study was conducted in 16 MMT clinics in Guangdong, China. Data on the clients’ demographic characteristics; drug-related behavior; HIV, HCV, and urine morphine test results; and daily methadone doses were collected. The outcomes were time to recurrent relapse and time to dropout. A joint frailty model was used to explore factors jointly associated with recurrent relapse and dropout. The hazard ratios (HRs) of the covariates in the multivariable model were adjusted, with HR > 1 indicating a faster time to recurrent relapse and dropout. ResultsAmong 1539 clients, 39.5% had ≥ 2 relapse events, and 90.8% of the clients dropped out. A high attendance rate was protective for recurrent relapse (HR50–80%=0.63, 95% CI: 0.51, 0.79; HR>80%=0.35, 95% CI: 0.28, 0.44) and dropout (HR50–80%=0.56, 95% CI: 0.47, 0.68; HR>80%=0.27, 95% CI: 0.23, 0.33). Being married (HR=0.80, 95% CI: 0.67, 0.96), having a fair relationship with family (HR=0.79, 95% CI: 0.67, 0.93) and drug injection (HR=0.80, 95% CI: 0.67, 0.96) were also protective for recurrent relapse. Female (HR=0.64, 95% CI: 0.50, 0.82) and a high methadone dose (≥60 ml/day; HR=0.79, 95% CI: 0.65, 0.96) were protective for dropout, and a longer traveling time to the clinic (>60 min; HR=1.59, 95% CI: 1.20, 2.10) was associated with an increased risk of dropout. ConclusionsIt is common for clients to experience recurrent relapse and dropout. The findings suggest that MMT clinics should provide holistic interventions and appropriate methadone doses for clients to improve treatment compliance.

Biochemical Differences Between High and Low Dose Methadone Clients on Stable Maintenance Therapy

Biochemical Differences Between High and Low Dose Methadone Clients on Stable Maintenance Therapy

The prevalence of constipation and its relation to sweet taste preference among patients receiving methadone maintenance treatment

BackgroundPreference for sweet-tasting foods, weight gain, and constipation characterize patients receiving methadone maintenance treatment (MMT). The prevalence of constipation in MMT and its relation to preference for sweet taste and body mass index (BMI) are undetermined. MethodsA random sample of 83 patients was interviewed for constipation with the Patient Assessment Constipation Quality of Life (PAC-QOL) questionnaire. They rated taste intensity and reward of sweet, salty, and sour solutions by means of a nine-point Likert scale. Data on their BMI, drugs in urine, methadone dose, and serum levels were analyzed. ResultsForty-two patients reported minimum to severe constipation. They characterized as having longer durations of opioid usage before MMT and worse sleep quality than non-constipated patients (logistic regression). Constipation intensity was inversely correlated with duration in MMT and linearly correlated with the Patient Assessment Constipation Quality of Life score. Patients with constipation rated reward to sweet taste significantly higher with no differences in taste intensity compared to non-constipated patients. Patients with high methadone serum levels (≥750 ng/mL) rated taste intensity significantly lower compared to those with normal methadone serum levels (<750 ng/mL), and the lowest rates were reported among patients with no constipation and high methadone serum levels. ConclusionsConstipation was highly prevalent among MMT patients and associated with poor sleep and lower quality of life. The relation to preference for sweets, as reflected by higher reward rating, strongly supports the need for nutritional intervention to alleviate constipation symptoms and improve quality of life and sleep.

Low-dose Buprenorphine Initiation in Hospitalized Adults With Opioid Use Disorder: A Retrospective Cohort Analysis.

Patients with opioid use disorder (OUD) can initiate buprenorphine without requiring a withdrawal period through a low-dose (sometimes referred to as "micro-induction") approach. Although there is growing interest in low-dose buprenorphine initiation, current evidence is limited to case reports and small case series. We performed a retrospective cohort study of patients with OUD seen by a hospital-based addiction medicine consult service who underwent low-dose buprenorphine initiation starting during hospital admission. We then integrated our practice-based experiences with results from the existing literature to create practice considerations. Sixty-eight individuals underwent 72 low-dose buprenorphine initiations between July 2019 and July 2020. Reasons for low-dose versus standard buprenorphine initiation included co-occurring pain (91.7%), patient anxiety around the possibility of withdrawal (69.4%), history of precipitated withdrawal (9.7%), opioid withdrawal intolerance (6.9%), and other reason/not specified (18.1%). Of the 72 low-dose buprenorphine initiations, 50 (69.4%) were completed in the hospital, 9 (12.5%) transitioned to complete as an outpatient, and 13 (18.1%) were terminated early. We apply our experiences and findings from literature to recommendations for varied clinical scenarios, including acute illness, co-occurring pain, opioid withdrawal intolerance, transition from high dose methadone to buprenorphine, history of precipitated withdrawal, and rapid hospital discharge. We share a standard low-dose initiation protocol with potential modifications based on above scenarios. Low-dose buprenorphine initiation offers a well-tolerated and versatile approach for hospitalized patients with OUD. We share lessons from our experiences and the literature, and provide practical considerations for providers.

Methadone overdose in patients following methadone mainte- nance treatment:A three years overview in the district of Bari (South-Italy).

Methadone maintenance treatment (MMT) is reco-gnized as a reference treatment for opioid dependence. According to Italian Law, at the beginning of the treatment patients must receive medication under the supervision of a physician, to avoid overdose. After a period of stability, patients could be allowed to take methadone at home in pre-arranged and personalized concentrations, in order to empower their self-responsibility. The aim of the present investigation is to underline the presence of a "glitch in the system" of the MMT. In the last three years, 7 forensic autopsies and toxi-cological analysis on corpses of regular opioid users were performed into the Institute of Legal Medicine of Bari. Therefor an improvement of the MMT's guideline is needed to reduce methadone overdose deaths in future. In all these cases very high methadone concentration in blood were found. All the 7 subjects were following a MMT in a Public Health Institute and the cause of death was respiratory depression by overdose of methadone in 6 cases.

Endocrinopathies Associated With High Dose Methadone

Abstract Introduction: The opioid epidemic is a public health crisis and clinicians should be aware of the many under-recognized endocrinopathies associated with opioids. Herein, we present a case that exemplifies the endocrine-related adverse effects of methadone therapy. Clinical Case: A 43-year-old Caucasian female with chronic back pain with opioid dependence, high dose methadone use (195 mg daily), and diabetes presented with refractory hypoglycemia. She was diagnosed with ketone prone diabetes eight months prior. She had since been weaned off insulin and her most recent HbA1c was 4.2%. During this time, she had an intentional weight loss of 60 pounds. On examination, she had bilateral lower extremity pitting edema with scaly plaques on the extremities. Laboratory tests showed C-peptide of 0.8 (0.9–7.1 ng/mL), insulin level of &amp;lt; 2 (3–25 mcIntUnits/mL), proinsulin of 4.6 (&amp;lt;18.8 pMol/L) with concurrent glucose of 48 mg/dl. She failed the ACTH stimulation test with 60 minute cortisol of 16.8 mcg/dL and was started on prednisone for adrenal insufficiency (AI). The pituitary and adrenal were normal on imaging. Her albumin was 1.5 (3.7–5.5 gm/dL) and she had vitamin and micronutrient deficiencies including copper, zinc, thiamine, selenium, and vitamin A. The insulin antibody test, paraneoplastic panel, celiac panel, A1 antitrypsin test, EGD, and colonoscopy were all non-revealing. A liver biopsy showed glycogenic hepatopathy. She improved clinically after prednisone initiation and treatment of malnutrition. The hypoglycemia improved but did not resolve as she refused to reduce methadone dose. Discussion: The proposed mechanism of opioid-induced AI is the inhibitory effect on the hypothalamic-pituitary-adrenal axis, similar to the effect on the gonadal axis which causes hypogonadism. The risk for hypoglycemia is increased in patients taking more than 40 mg of oral methadone per day, and although the mechanism remains unclear, it is independent of adrenal function. Our patient had adrenal insufficiency and hypoglycemia related to methadone, which was further complicated by malnutrition. The glycogenic hepatopathy is a benign reversible condition that is believed to be a consequence of fluctuation in glucose levels. Conclusion: Given the life-threatening nature of adrenal crisis and the overlap in symptomatology with opiate overdose, clinicians should be prompt in evaluating for endocrinopathies in patients on chronic high dose opiates, and patients should be appropriately counseled on the potential consequences of methadone use.

Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway

BackgroundThere is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments.MethodsThis naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data.ResultsThe mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p < 0.001); the specific subjective withdrawal symptoms of anxiety (p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049).ConclusionsThe findings suggest that the patient’s self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.

Strategies for Transfer From Methadone to Buprenorphine for Treatment of Opioid Use Disorders and Associated Outcomes: A Systematic Review.

Objectives:To review the currently available evidence on transfer strategies from methadone to sublingual buprenorphine used in clinical trials and observational studies of medication for opioid use disorder treatment, and to consider whether any strategies yield better clinical outcomes than others.Methods:Six medical and public health databases were searched for articles and conference abstracts. The Cochrane Central Register of Controlled Trials and the World Health Organization International Clinical Trials Registry Platform were used to identify unpublished trial results. Records were dually screened, and data were extracted and checked independently. Results were summarized qualitatively and, when possible, analyzed quantitatively.Results:Eighteen studies described transfer from methadone to buprenorphine. Transfer protocols were extremely varied. Most studies reported successful rates of transfer, even among studies involving transfer from high methadone doses, although lower pretransfer methadone dose was significantly associated with higher rate of successful transfer. Precipitated withdrawal was not reported frequently. A range of innovative approaches to transfer from methadone to buprenorphine remains untested.Conclusions:Few studies have used designs that enable comparison of different approaches to transfer patients from methadone to buprenorphine. Most international clinical guidelines provide recommendations consistent with the available evidence. However, clinical guidelines should be perceived as providing “guidance” rather than “protocols,” and clinicians and patients need to exercise judgment when attempting transfers.

Effect of methadone on QTc in infants

ObjectiveMethadone has been associated with prolongation of the QTc interval (QTc) on electrocardiogram (ECG). In infants, the effects of methadone on the QTc are not well described. Our study's objective is to evaluate the QTc in infants being treated with methadone. MethodsWe conducted a retrospective study in infants receiving methadone. We collected demographic data, methadone dose, and QTc. A blinded-to-disease-state pediatric electrophysiologist determined the QTc. Baseline ECG was defined as an ECG obtained while not on methadone therapy, and QTc on baseline ECG was compared with treatment QTc. A significant change was defined as any absolute QTc greater than 500 or a QTc greater than 460 with an increase from baseline of greater than 40 ms. ResultsA total of 44 infants comprised the study population. The mean gestational age was 32.3 ± 5.51 weeks. The median age of initiation was 66 days. The median dose was 0.52 mg/kg/day in oral methadone equivalents. Nine patients were on high dose methadone (>1 mg/kg/day in oral methadone equivalents). The mean baseline QTc was 421 ± 27 and the mean change on methadone was −2 ms. No patient had a QTc greater than 500 on methadone. One patient had a QTc of 467 and 46 ms change from baseline, with no clinically significant impact. ConclusionIn our study population, methadone did not significantly prolong the QTc. Further prospective study is warranted to determine the utility and frequency of ECGs in infants receiving methadone.

OPRM1 and CYP3A4 association with methadone dose in Iranian patients undergoing methadone maintenance therapy

Background Investigations proposed that genetic polymorphisms within proteins in methadone pharmacokinetic and pharmacodynamics are critical factors in determination of methadone dose in methadone maintenance therapy (MMT). Objective This study aimed to assess the associations between two polymorphisms, CYP3A4 (rs2740574) and OPRM1 (rs1799971), with dose of methadone in Iranian patients undergoing MMT. Methods A total of 124 Iranian male subjects aged 18–65 years old who were confirmed to be addicted by the addiction diagnostic tests and underwent MMT were assessed. Patients were divided into three groups of low (less than 40 mg/day), moderate (more than 40 mg/day and less than 110 mg/day) and high (more than 110 mg/day) methadone dose consumption. DNAs of included patients were extracted from their blood samples and were assessed for CYP3A4 and OPRM1 polymorphisms. Results Results showed that there was no significant association between the studied polymorphisms and methadone dose in Iranian addicted patients underwent MMT (P > 0.05). Conclusions CYP3A4 and OPRM1 single variations cannot explain variability in methadone dosage in MMT. Studying the interactions of more genetic factors in larger samples may elucidate factors influencing the required dose of methadone and better individualized therapy.

Associations between opioid dependence and sweet taste preference.

Past research suggests that people with opioid dependence show increased consumption of sweet food, but it is unclear if this is influenced by altered taste preference and/or taste perception. We tested whether people prescribed opioid substitution therapy (OST) exhibited a shift in preference towards sweeter flavours, and altered perception of sweetness, and explored whether these measures of taste preference/perception were associated with measures of opioid use. Three groups of participants (people prescribed OST, n=36; people with past opioid dependence, but now abstinent from all opioids, n=18; and controls with no history of substance dependence other than nicotine, n=29) provided ratings of "sweetness", "liking", and "desire" of 4 solutions with varying concentrations of sucrose. We did not find significant differences between groups in the effect of sucrose concentration on "sweetness", "liking", or "desire" ratings. However, among those prescribed OST, frequency of recent illicit opioid use was associated with reduced perception of "sweetness" of low sucrose concentrations. Higher methadone dose was associated with a shift towards liking sweeter concentrations. Among those with past opioid dependence, longer duration of abstinence from opioids was associated with a shift towards liking sweeter concentrations. Among people currently dependent on opioids, reduced sensitivity to low levels of sweetness and increased preference for sweeter flavours may be associated with increased dependence on opioids. Among those who have ceased opioid use, the association between preference for sweeter flavours and duration of abstinence is a novel finding that deserves further investigation.

Higher methadone dose reduces risky drug injecting behaviours among methadone clients in Myanmar

BackgroundHIV prevalence rate among people who inject drugs (PWIDs) in Myanmar is marginally high (34.9%). HIV transmission can be reduced and prevented through harm reduction programs such as methadone maintenance treatment (MMT) and needle syringe exchange program (NSEP). We sought to determine the relationship between methadone dose and injecting behaviours among clients enrolled in the MMT program in Myanmar. MethodA total of 210 MMT clients, who had a minimum of six-month methadone treatment history, were recruited from five cities through stratified random sampling for this cross-sectional study. A semi-structured questionnaire with the timeline flow back (TLFB) scale was administered. Respondents were also screened for illicit drug use. ResultsAlmost two-thirds (63.5%, n=132) received less than or equal to 80mg/day of methadone dose, and 36.5% (n=76) received more than 80mg of methadone daily, while the sample average daily methadone dose in this study was 83mg (ranging from 20mg to 300mg per day). The results indicated that methadone dose was associated with having HIV infection, antiretroviral therapy (ART) and tuberculosis (TB) treatment history, heroin injection history in the last 30 days, needle sharing history, addiction severity on employment, as well as THC (cannabis) and benzodiazepine use history (p<0.05). In addition, those who received a high methadone dose (more than 80mg/day) reduced their heroin injection use by 4 times compared to heroin injection frequency of respondents on low methadone dose (injection IRR=0.0029 vs. 0.0118, p=0.0000). Meanwhile, those who had HIV on high methadone dose were 2.6 times more likely to report reduction in risky injecting behaviours compared to low methadone dose. ConclusionA higher dose of methadone on prescription (more than 80mg/day) seems to reduce risky HIV injecting behaviours among both HIV negative and positive clients in MMT programs in Myanmar.

Cytotoxic and Senolytic Effects of Methadone in Combination with Temozolomide in Glioblastoma Cells.

Methadone is an analgesic drug used for pain treatment and heroin substitution. Recently, methadone has been proposed to be useful also for cancer therapy, including glioblastoma multiforme (GBM), the most severe form of brain cancer, because experiments on cultured glioma cells treated with doxorubicin showed promising results. Doxorubicin, however, is not used first-line in GBM therapy. Therefore, we analyzed the cytotoxic effect of methadone alone and in combination with temozolomide, a DNA-alkylating drug that is first-line used in GBM treatment, utilizing GBM-derived cell lines and a human fibroblast cell line. We show that methadone is cytotoxic on its own, inducing apoptosis and necrosis, which was observed at a concentration above 20 µg/mL. Methadone was similar toxic in isogenic MGMT expressing and non-expressing cells, and in LN229 glioblastoma and VH10T human fibroblasts. The apoptosis-inducing activity of methadone is not bound on the opioid receptor (OR), since naloxone, a competitive inhibitor of OR, did not attenuate methadone-induced apoptosis/necrosis. Administrating methadone and temozolomide together, temozolomide had no impact on methadone-induced apoptosis (which occurred 3 days after treatment), while temozolomide-induced apoptosis (which occurred 5 days after treatment) was unaffected at low (non-toxic) methadone concentration (5 µg/mL), and at high (toxic) methadone concentration (20 µg/mL) the cytotoxic effects of methadone and temozolomide were additive. Methadone is not genotoxic, as revealed by comet and γH2AX assay, and did not ameliorate the genotoxic effect of temozolomide. Further, methadone did not induce cellular senescence and had no effect on temozolomide-induced senescence. Although methadone was toxic on senescent cells, it cannot be considered a senolytic drug since cytotoxicity was not specific for senescent cells. Finally, we show that methadone had no impact on the MGMT promoter methylation. Overall, the data show that methadone on glioblastoma cells in vitro is cytotoxic and induces apoptosis/necrosis at doses that are above the level that can be achieved in vivo. It is not genotoxic, and does not ameliorate the cell killing or the senescence-inducing effect of temozolomide (no synergistic effect), indicating it has no impact on temozolomide-induced signaling pathways. The data do not support the notion that concomitant methadone treatment supports temozolomide-based chemotherapy.

Continued Use of Illicit Substance among Methadone Treatment Patients in Primary Health Care Clinics in East Coast Region of Malaysia

ABSTRACTStudies investigating the continued use of illicit substances among patients in Methadone Maintenance Treatment (MMT) programs are limited. This study aimed to determine the association of methadone dose with illicit substance misuse among MMT patients in East Coast Region of Malaysia. Validated substance use pattern questionnaire was used to fulfill the study objectives. 55% (n = 130/237) of the respondents received a ≤ 50 mg methadone dose daily. Low methadone dose (≤50 mg/daily) was associated with opiate use in the last 30 days, while high methadone dose (>50 mg/daily) was associated with methamphetamine injection in the last 30 days (OR: 1.97; 1.01–3.82; p< .044). An optimum methadone maintenance dose is deemed appropriate to reduce use of illicit opiates, and necessary psychosocial intervention to reduce methamphetamine injection behavior is suggested.

Methadone-Related Delirium: Prevalence, Causes, and Outcomes.

Goals consist of determining 5-year prevalence and recurrence of methadone-related delirium (MRD), along with causes, treatments, and outcomes. Sample comprised 81 patients in methadone maintenance treatment. Criteria for MRD encompassed delirium with high methadone serum levels plus alleviation of delirium upon lowering methadone serum levels. MRD occurred in 14 cases who had 25 episodes. MRD precipitants included physician prescribing (i.e., excessive methadone or medications slowing methadone metabolism), drug misuse, and renal-fluid alterations. Social affiliation (housing with family, intimate partner) reduced MRD; employment increased MRD. Recovery occurred in 23/25 episodes of MRD; two episodes progressed to dementia. Obtaining serum methadone levels fostered prompt recognition.

Opioid agonist treatment dosage and patient-perceived dosage adequacy, and risk of hepatitis C infection among people who inject drugs.

Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in opioid agonist treatment is unclear. We investigated the joint association of prescribed dosage of opioid agonist treatment and patient-perceived dosage adequacy with risk of HCV infection among people who inject drugs. We followed prospectively people who inject drugs at risk of acquiring HCV infection (who were RNA negative and HCV-antibody negative or positive) in Montréal, Canada (2004-2017). At 6-month, then 3-month intervals, participants were tested for HCV antibodies or RNA, and completed an interviewer-administered behavioural questionnaire, reporting the following: current exposure to opioid agonist treatment (yes/no), prescribed dosage either high (methadone ≥ 60 mg/d or buprenorphine ≥ 16 mg/d) or low, and perceived dosage adequacy (adequate/inadequate). We then assigned participants to 1 of 5 exposure categories: no opioid agonist treatment, high dosage of opioid agonist treatment perceived to be adequate, high dosage perceived to be inadequate, low dosage perceived to be adequate or low dosage perceived to be inadequate. To estimate associations between categories of opioid agonist treatment dosage and incident HCV infection, we conducted Cox regression analyses, adjusting for multiple confounding factors. Of 513 participants (median age 35.0 yr, 77.6% male), 168 acquired HCV over 1422.6 person-years of follow-up (incidence 11.8/100 person-years, 95% confidence interval [CI] 10.1-13.7). We observed a gradient in the relative risks of HCV infection across categories of opioid agonist treatment dosage. Compared with people who inject drugs not receiving opioid agonist treatment, adjusted hazard ratios were 0.43 (95% CI 0.23-0.84) for those receiving high dosages perceived to be adequate, 0.61 (95% CI 0.25-1.50) for those receiving high dosages perceived to be inadequate, 1.22 (95% CI 0.74-2.00) for those receiving low dosages perceived to be adequate and 1.94 (95% CI 1.11-3.39) for those receiving low dosages perceived to be inadequate. Risk of HCV infection varies considerably according to dosage of opioid agonist treatment and patient-perceived adequacy, with associations indicating both protective and harmful effects relative to no exposure to opioid agonist treatment.

Prophylactic Gabapentin Combined with Methadone Improves Overall Health in Patients Undergoing Chemoradiation for Head and Neck Cancer While Reducing Use of Opioids with High Abuse Potential: Early Results of a Prospective Randomized Trial

Oral mucositis occurs in the majority of patients (pts) undergoing chemoradiation therapy (CRT) for head and neck cancer (HNC). The Oral Mucositis Daily Questionnaire (OMDQ) is a validated survey for HNC patient pain. Gabapentin (GABA) has been used concurrently with opioids to improve pain control in pts with HNC. Methadone (MTD) is a low abuse potential opioid that is used for neuropathic pain. This single center prospective randomized study was undertaken to compare analgesia regimens for pts undergoing CRT. Hypothesis: We hypothesized pts treated with GABA would have improved pain control and delay the onset of narcotic requirement, and the addition of MTD would provide improved pain control. Pts with Stage II-IV HNC who were treated with definitive CRT were randomized to one of two pain regimens: 1) High-dose GABA (900mg TID) with hydrocodone-acetaminophen followed by transdermal fentanyl as needed (HD-HAF) or 2) Low-dose GABA (300mg TID) with methadone (5-15mg BID) and oxycodone as needed (LD-MTD). Pts were stratified by bilateral or unilateral radiation. At baseline and weekly on-treatment visits, clinical data including narcotic use was recorded and OMDQ was administered. Average daily narcotic use was converted to oral morphine milligram equivalents. Two sided T and Fischer exact tests were performed. A total of 60 pts were randomized; at the time of analysis not all patients had completed their scheduled evaluations. Median dose to the primary was 70 Gy. There were no attributable grade 3 adverse events. Approximately half of HD-HAF and three quarters of LD-MTD required a narcotic during CRT. The time to first narcotic was approximately 4.5 weeks for both groups. LD-MTD had better Overall Health at week 7 vs. HD-HAF (p<0.05). This study demonstrates that both pain regimens are safe and well tolerated. Methadone is associated with better overall health at the end of treatment for pts undergoing CRT. Our next study will utilize high dose GABA and methadone. Implications for practice or research: Methadone, as a low abuse potential narcotic, combined with prophylactic GABA can improve overall health at the end of CRT for HNC. Further escalating GABA dose may optimize the therapeutic benefit of MTD and will be tested in a future study.

Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a Tertiary Children's Health Service.

Methadone has the potential to assist in the management of pain in children with life-limiting illness, but its use is limited by its complex pharmacokinetic profile and limited research on its use in children. This is a retrospective review of the use of methadone as an analgesic in 16 children with life-limiting illness. Efficacy, dosing and side effect profile were analysed. Fifteen (94%) patients had improvements in their analgesia with minimal observed adverse effects. Patients were either rapidly converted from a prior opioid in one change or received methadone as an adjunct medication. Conversions were calculated using ratios frequently in the range of 10:1 to 20:1 from the oral morphine equivalent total daily dose (MEDD). Adjunct initial dosing was a low dose trial, often beginning with 1 mg at night. Only two patients required a dose adjustment due to side effects attributed to methadone. This was despite the cohort having significant underlying illnesses, extensive concurrent medications, and high methadone dosing where needed. Analysis of dosing and ratios indicates that an individualised approach is required. Based on this and on the infrequency of methadone use in this population, specialist assistance with dosing is recommended. Further research, including prospective and pharmacokinetic studies, is recommended.