Methadone Initiation Research Articles

The effect of oral methadone on the QTc interval in cancer pain patients.

The QTc prolongation effect of methadone has been extensively studied at higher doses commonly used in opioid dependence maintenance therapy, but evidence remains limited regarding its impact at the lower doses typically prescribed for cancer pain. This study aims to evaluate the effect of oral methadone on QTc intervals in cancer pain patients. A retrospective analysis was performed on adult patients initiated on oral methadone therapy for cancer. Pre- and post-methadone QTc intervals, obtained within six months before and between six to twelve months after methadone initiation, respectively, were compared. The proportion of patients with QTc intervals greater than 450 msec and 500 msec before and after methadone therapy were compared. Among the total of 310 patients, the mean pre-methadone QTc was 384.5 ± 37.8 msec (95% CI 380.3, 388.7) and the mean post-methadone QTc was 388.5 ± 43.4 msec (95% CI 383.6, 393.3). No statistically significant difference in QTc interval was observed (p = 0.1). The proportion of patients with a QTc greater than 450 msec and 500 msec pre- and post-methadone were also not statistically different. Lower doses of oral methadone for cancer pain do not result in significant QTc prolongation.

Early Results of Implementing Rapid Methadone Titration for Hospitalized Patients: A Case Series.

With the increase in illicit fentanyl use in the USA, hospitals face challenges managing opioid withdrawal and opioid use disorder (OUD). To improve opioid withdrawal and OUD treatment among hospitalized patients with daily fentanyl use, we developed a rapid methadone titration (RMT) protocol. We describe development, implementation, and outcomes during the first 12weeks. We analyzed electronic health record data of hospitalizations seen by the Addiction Consult Team (ACT) for methadone initiation between 9/11/23 and 12/3/23. Adults aged 18-64 reporting daily fentanyl use, desiring methadone, and without end-stage organ damage or critical illness were RMT eligible. We characterized patients who received RMT, abstracting demographic and clinical characteristics, adverse events graded by the Common Terminology Criteria for Adverse Events(CTCAE), and methadone and additional full agonist opioid (FAO) dosing. Our primary outcome was adverse events. Secondary outcomes included median time to 100mg of methadone, FAO dosing, and self-directed discharge. ACT assessed 55 hospitalizations representing 47 patients for RMT eligibility. Among these, 19 (34.5%) hospitalizations representing 17 patients were eligible for and received RMT. Four (21.2%) hospitalizations that received RMT had sedation events, and all were mild or moderate grade by CTCAE. Hospitalizations achieved a median methadone dose of 100mg by day 6, with FAO doses peaking on day 5. One (5.3%) hospitalization had a self-directed discharge. With careful patient selection and ACT evaluation, a RMT protocol for hospitalized patients with fentanyl use disorder experienced few adverse events other than mild-moderate sedation, even among those receiving FAO and those with concurrent substance use disorders.

Low-dose add-on methadone for cancer pain management: a retrospective analysis of 102 Japanese patients.

Methadone was introduced in 2013 for the treatment of intractable cancer pain in Japan and is indicated for patients receiving opioid doses ≧60mg/day as an oral morphine equivalent. Low-dose (≦10mg/day) add-on methadone to prior opioids has been reported from European countries to successfully relieve various types of intractable cancer pain; however, there are few reports of such use in Japan. The aim of this study was to analyze more than a hundred cases with low-dose add-on methadone to treat intractable pain in Japanese cancer patients. All cases in which 5 or 10mg/day of methadone was added to prior opioids by the Palliative Care Team or Division of Palliative Medicine in our hospital during the period between April 2016 and September 2023 were extracted and analyzed retrospectively on electrical medical charts. A total of 102 cases were extracted with a male-to-female ratio of60:42, and the age (mean±SD) was 62.8±14.7years old. Methadone was introduced in an inpatient setting to 86 patients. The major pathologies that caused intractable pain were spinal metastases in 48, pelvis or pelvic floor lesions in 29 and pleural and/or chest wall lesions in 16. The most common mechanism of pain was the mixture of somatic and neuropathic components. The major opioids administered prior to methadone included tapentadol in 46 patients, hydromorphone in 36 and oxycodone in 19. The dose of the prior opioids [median, (interquartile range: IQR)] was 97, (62.8-167.3) (range: 15-1313) mg/day of oral morphine equivalent. Radiotherapy, chemotherapy and nerve blocks were performed as concomitant therapies in 48, 22 and 11 patients, respectively (with some overlap). The number of rescue doses [median (IQR)] was significantly decreased from three (two to five) on the day before methadone to one (zero to four) after seven days from methadone initiation. The side effects leading to discontinuation of methadone were drowsiness in three cases, nausea in three cases and dizziness in one case (with some overlap). Compared with complete switching from other opioids, low-dose add-on methadone can reduce the possibility of major dose discrepancies and can be quickly adjusted by combined opioid reduction/increase. Low-dose add-on methadone can be an effective and safe method for intractable cancer pain.

Addiction Consult Service and Inpatient Outcomes Among Patients with OUD

BackgroundDespite rising hospitalizations for opioid use disorder (OUD), rates of inpatient medications for OUD (MOUD) initiation are low. Addiction consult services (ACSs) facilitate inpatient MOUD initiation and linkage to post-discharge MOUD, but few studies have rigorously examined ACS OUD outcomes.ObjectiveTo determine the association between ACS consultation and inpatient MOUD initiation, discharge MOUD provision, and post-discharge MOUD linkage.DesignRetrospective study comparing admissions that received an ACS consult and propensity score–matched historical control admissions.SubjectsOne hundred admissions with an OUD-related diagnosis, of patients not currently receiving MOUD who received an ACS consult, and 100 matched historical controls.InterventionConsultation from an interprofessional ACS offering expertise in MOUD initiation and linkage to post-discharge MOUD.Main MeasuresThe primary outcome was inpatient MOUD initiation (methadone or buprenorphine). Secondary outcomes were inpatient buprenorphine initiation, inpatient methadone initiation, discharge prescription for buprenorphine, linkage to post-discharge MOUD (buprenorphine prescription within 60 days and new methadone administration at a methadone program within 30 days after discharge), patient-directed discharge, 30-day readmission, and 30-day emergency department (ED) visit.Key ResultsAmong 200 admissions with an OUD-related diagnosis, those that received an ACS consultation were significantly more likely to have inpatient MOUD initiation (OR 2.57 [CI 1.44–4.61]), inpatient buprenorphine initiation (OR 5.50 [2.14–14.15]), a discharge prescription for buprenorphine (OR 17.22 [3.94–75.13]), a buprenorphine prescription within 60 days (22.0% vs. 0.0%, p < 0.001; of those with inpatient buprenorphine initiation: 84.6% vs. 0.0%), and new methadone administration at a methadone program within 30 days after discharge (7.0% vs. 0.0%, p = 0.007; of those with inpatient methadone initiation: 19.4% vs. 0.0%). There were no significant differences in other secondary outcomes.ConclusionsThere was a strong association between ACS consultation and inpatient MOUD initiation and linkage to post-discharge MOUD. ACSs promote the delivery of evidence-based care for patients with OUD.

Methadone Initiation in the Emergency Department for Opioid Use Disorder.

Overdose deaths from high-potency synthetic opioids, including fentanyl and its analogs, continue to rise along with emergency department (ED) visits for complications of opioid use disorder (OUD). Fentanyl accumulates in adipose tissue; although rare, this increases the risk of precipitated withdrawal in patients upon buprenorphine initiation. Many EDs have implemented medication for opioid use disorder (MOUD) programs using buprenorphine. However, few offer methadone, a proven therapy without the risk of precipitated withdrawal associated with buprenorphine initiation. We describe the addition of an ED-initiated methadone treatment pathway and compared its 72-hour follow-up outpatient treatment engagement rates to our existing ED-initiated buprenorphine MOUD program. We expanded our ED MOUD program with a methadone treatment pathway. From February 20-September 19, 2023, we screened 20,504 ED arrivals; 5.1% had signs of OUD. We enrolled 61 patients: 28 in the methadone; and 33 in the buprenorphine pathways. For patients who screened positive for opioid use, shared decision-making was employed to determine whether buprenorphine or methadone therapy was more appropriate. Patients in the methadone pathway received their first dose of up to 30 milligrams (mg) of methadone in the ED. Two additional methadone doses of up to 40mg were dispensed at the time of the ED visit and held in the department, allowing patients to return each day for observed dosing until intake at an opioid treatment program (OTP). We compared 72-hour rates of outpatient follow-up treatment engagement at the OTP (for those on methadone) or at the addiction treatment center (ATC) (for those on buprenorphine) for the two treatment pathways. Of the 28 patients enrolled in the methadone pathway, 12 (43%) successfully engaged in follow-up treatment at the OTP. Of the 33 patients enrolled in the buprenorphine pathway, 15 (45%) successfully engaged in follow-up treatment at the ATC (relative risk 1.06; 95% confidence interval 0.60-1.87). Methadone initiation in the ED to treat patients with OUD resulted in similar 72-hour follow-up outpatient treatment engagement rates compared to ED-buprenorphine initiation, providing another viable option for MOUD.

Chart Review and Practical Recommendations for the Use of Methadone as an Alternative to Opioid Rotation in the Management of Cancer-Related Pain

Abstract Introduction Palliative care, with a focus on enhancing the quality of life for individuals facing life-limiting illnesses, relies on effective pain management as a fundamental component. Opioids, particularly methadone, play a crucial role in addressing moderate to severe pain in palliative care due to their unique pharmacological properties. Methadone, a long-acting opioid agonist and N-methyl-D-aspartate receptor antagonist, is valuable for treating both nociceptive and neuropathic pain. However, the transition to methadone from other opioids requires careful consideration. Objectives This study examines the use of methadone as an alternative to morphine or fentanyl for managing refractory cancer pain in a tertiary care hospital in India. Methods We conducted a retrospective analysis of anonymized medical records of cancer patients initiated on oral methadone for pain management at a tertiary cancer center's palliative medicine outpatient clinic from February 2020 to June 2021. Data included demographic characteristics, pain descriptions, concurrent analgesic use, reasons for transitioning to methadone, rotation methods, methadone dosages, clinical outcomes, adverse effects, and treatment discontinuations. Patients were routinely followed up, with pain scores, morphine equivalent daily doses, and methadone requirements recorded at each visit. Results Forty-four patients received methadone, either as a coanalgesic (41/44) or primary opioid (3/44). Refractory cancer pain, with a neuropathic component, was the predominant indication for methadone use. Following the methadone initiation, all patients experienced significant pain relief. Median daily methadone dose increased from 5 to 7.5 mg after 1 week. Adverse effects were minimal, with one patient experiencing QTc interval prolongation. Patient-specific factors often necessitated deviations from equianalgesic conversion tables in determining methadone dosages. Conclusion Methadone offers a viable option for refractory cancer pain when conventional treatments fall short. Physicians should prioritize personalized titration and thorough assessment during opioid rotation, rather than relying solely on conversion tables. Further research is needed to explore alternative approaches for opioid rotation and to expand our understanding of methadone's optimal use in cancer pain management.

S50 - Effectiveness of Rapid Inpatient Initiation of Methadone for Pregnant Women With Opioid Use Disorder

S50 - Effectiveness of Rapid Inpatient Initiation of Methadone for Pregnant Women With Opioid Use Disorder

Prescription psychostimulant use, admissions and treatment initiation and retention in pregnant people with opioid use disorder.

While attention deficit hyperactivity disorder is common among people with addiction, the risks and benefits of attention deficit hyperactivity disorder medication in pregnant people with opioid use disorder are poorly understood. Here, using US multistate administrative data, we examined 3,247 pregnant people initiating opioid use disorder treatment, of whom 5% received psychostimulants. Compared to peers not receiving psychostimulants, the psychostimulant cohort had greater buprenorphine (adjusted relative risk 1.81 (1.50-2.18)) but lower methadone initiation (adjusted relative risk 0.39 (0.19-0.78)). Among psychostimulant recipients who initiated buprenorphine, we observed lower buprenorphine discontinuation associated with the psychostimulant cohort compared to nonrecipients (adjusted hazard ratio 0.77 (0.67-0.88)). In within-person case-crossover analyses, person-days defined by psychostimulant fills were associated with fewer substance use disorder-related admissions compared to days without fills (odds ratio 0.50 (0.33-0.76)). Overall, our data suggest that psychostimulant use in pregnancy may be associated with increased buprenorphine initiation, decreased methadone initiation and improved buprenorphine retention. Decreased substance use disorder-related admissions were associated with person-days of psychostimulant receipt, although other risks of psychostimulant use in pregnancy warrant further investigation.

Piloting a Hospital-Based Rapid Methadone Initiation Protocol for Fentanyl.

Treating acute opioid withdrawal and offering medications for opioid use disorder (OUD) is critical. Hospitalization offers a unique opportunity to rapidly initiate methadone for OUD; however, little clinical guidance exists. This report describes our experience during the first 9 months following introduction of a hospital-based rapid methadone initiation protocol. We conducted a retrospective chart review of hospitalized patients with OUD seen by our interprofessional addiction medicine consult service at an urban academic center between December 2022 and August 2023. We identified patients who initiated methadone using the rapid methadone initiation protocol, which includes dose recommendations (maximum 60 mg day 1, 70 mg day 2, 80 mg day 3, 100 mg days 4-7) and strict inclusion and exclusion criteria (end organ failure, arrhythmia, concurrent benzodiazepine or alcohol use, age >65). There were 171 patients that received methadone for OUD during the study period. Of those, 25 patients (15%) received rapid methadone initiation. The average total daily dose of methadone on days 1-7 was 53.0 mg, 69.2 mg, 75.4 mg, 79.5 mg, 87.1 mg, 92.2 mg, and 96.6 mg, respectively. There were no adverse events requiring holding a dose of scheduled methadone, naloxone administration, or transfer to higher level of care. A rapid methadone initiation protocol for OUD can be implemented in the inpatient setting. Patients up-titrated their methadone doses quicker than with traditional induction methods, and there were no serious adverse events. Appropriate patient selection may be important to avoid harms.

Differences in Inpatient Management of Cancer-Related Pain Among Patients with Opioid Use Disorder.

The management of cancer-related pain in patients with opioid use disorder (OUD) remains complex and often challenging for clinicians and patients. There is currently a paucity of data to guide best practices, and the evidence that exists is variably applied. In this hospital-based questionnaire, we sought to understand the variation in practice patterns among clinicians in palliative medicine, addiction medicine, and hospital medicine, in caring for this complex patient population. Sixty-two questionnaire responses were analyzed and variation was found in management of pain, as well as initiation or titration of buprenorphine and methadone. There was also a significant difference in postdischarge subspecialty follow-up. Furthermore, the findings suggest that buprenorphine and methadone may be underutilized in this population. Patients and clinicians may benefit from additional support and standardization of practices to best manage coexisting cancer-related pain and OUD.

1210 Initiation of Methadone for Refractory Restless Leg Syndrome with Significant Improvement of Symptoms

1210 Initiation of Methadone for Refractory Restless Leg Syndrome with Significant Improvement of Symptoms

North Carolina Medicaid System Perspectives on Substance Use Disorder Treatment Policy Changes During the COVID-19 Pandemic.

This study aimed to describe perspectives from stakeholders involved in the Medicaid system in North Carolina regarding substance use disorder (SUD) treatment policy changes during the coronavirus disease 2019 pandemic. We conducted semistructured interviews in early 2022 with state agency representatives, Medicaid managed care organizations, and Medicaid providers (n = 22) as well as 3 focus groups of Medicaid beneficiaries with SUD (n = 14). Interviews and focus groups focused on 4 topics: policies, meeting needs during COVID, demand for SUD services, and staffing. Overall, policy changes, such as telehealth and take-home methadone, were considered beneficial, with participants displaying substantial support for both policies. Shifting demand for services, staffing shortages, and technology barriers presented significant challenges. Innovative benefits and services were used to adapt to these challenges, including the provision of digital devices and data plans to improve access to telehealth. Perspectives from Medicaid stakeholders, including state organizations to beneficiaries, support the continuation of SUD policy changes that occurred. Staffing shortages remain a substantial barrier. Based on the participants' positive responses to the SUD policy changes made during the coronavirus disease 2019 pandemic, such as take-home methadone and telehealth initiation of buprenorphine, these changes should be continued. Additional steps are needed to ensure payment parity for telehealth services.

Novel Uses of Methadone Under the "72-Hour Rule" to Facilitate Transitions of Care and Low-Dose Buprenorphine Induction in an Outpatient Bridge Clinic.

Federal regulations restrict methadone for opioid use disorder (OUD) treatment to licensed opioid treatment programs (OTPs). However, providers in other settings can administer methadone for opioid withdrawal under the "72-hour rule" while linking to further care. Prior work has demonstrated that methadone initiation in a low-barrier bridge clinic is associated with high OTP linkage and 1-month retention rates. We describe 2 other novel applications of the 72-hour rule in which methadone withdrawal management facilitated linkage to inpatient hospitalization and outpatient buprenorphine induction. Patient 1 was a 46-year-old woman with OUD complicated by serious injection-related infections. Severe opioid withdrawal limited her ability to tolerate emergency department wait times and receive inpatient care. We administered methadone for opioid withdrawal in an outpatient bridge clinic immediately before emergency department referral; this enabled hospital admission for intravenous antibiotics and anticoagulation. Patient 2 was a 36-year-old man with OUD desiring buprenorphine treatment. He had been unable to complete traditional buprenorphine induction without experiencing precipitated withdrawal. Thus, we recommended a low-dose buprenorphine induction overlapping with a full opioid agonist. Given the patient's preference to stop using fentanyl immediately, he received 72 hours of methadone for withdrawal treatment during the induction phase and successfully transitioned to buprenorphine without significant concomitant fentanyl use. In addition to facilitating OTP linkage, on-demand 72-hour methadone administration for opioid withdrawal can reduce barriers to acute medical care and buprenorphine treatment.

Initiation and rapid titration of methadone and slow-release oral morphine (SROM) in an acute care, inpatient setting: a case series

BackgroundMethadone titration in an outpatient setting typically involves initiation with subtherapeutic doses with slow titration to mitigate the risks of respiratory depression and overdose. In pregnancy, and generally, subtherapeutic doses of methadone and slow titrations are associated with poorer outcomes in terms of treatment retention and ongoing illicit opioid use. We aim to describe rapid titration of OAT in an inpatient setting for pregnant injection opioid users with high opioid tolerance secondary to a fentanyl-based illicit drug supply.MethodsRetrospective case series of patients admitted to a tertiary center with a primary indication of opioid withdrawal and treatment for severe opioid use disorder in pregnancy. ResultsTwelve women received rapid methadone titrations with or without slow-release oral morphine for opioid use disorder during a total of fifteen hospital admissions. All women included in the study were active fentanyl users (12/12). Methadone dosing was increased rapidly with no adverse events with a median dose at day 7 of 65 mg (IQR 60–70 mg) and median discharge dose of 85 mg (IQR 70–92.5 mg) during their admission for titration. Slow-release oral morphine was used in half of the titration admissions (8/15) with a median dose of 340 mg (IQR 187.5–425 mg) at discharge. The median length of admission was 12 days (IQR 9.5–15).ConclusionsA rapid titration of methadone was completed in an inpatient setting with or without slow-release oral morphine, without adverse events showing feasibility of this protocol for a pregnant population in an inpatient setting. Patients achieved therapeutic doses of methadone (and/or SROM) faster than outpatient counterparts with no known adverse events.

Maternal Perspective of Inpatient Methadone Initiation: Opportunities to Increase Retention in Treatment.

Recent trends demonstrate increases in the rates of opioid use among pregnant and parenting women. Treatment for pregnant people with opioid use disorder (OUD) includes medications for OUD, like methadone, as well as comprehensive support services. Still, inpatient treatment engagement is suboptimal and treatment drop out is common. There is little research examining the maternal perspective of the inpatient methadone initiation experience. The primary aim of this qualitative methods study was to explore patient experience and perspective of the inpatient methadone initiation period. All participants were recruited from a single urban university affiliated hospital and OUD treatment program. Data were collected from 30 maternal participants in OUD treatment about their inpatient methadone initiation experience while pregnant using semistructured interviews. Thematic analyses were conducted using an inductive approach after an iterative process of code development and application among a multidisciplinary team of 3 coders. Validity was accounted for through 2 participant feedback interviews and study team review and discussion of findings. Four themes emerged from the maternal interview data: (1) Barriers to Inpatient Methadone Initiation, (2) Facilitators to Inpatient Methadone Initiation, (3) Transition From Hospital Inpatient to Outpatient or Residential OUD Treatment Services, and (4) Opportunities for Enhanced Clinical Support. Maternal participants reported multiple barriers and facilitators to inpatient care during methadone initiation, highlighting opportunities for improvement to effectively engage pregnant individuals in treatment.

(177) A Rapid Methadone Initiation Protocol for Stabilization of Opioid Withdrawal in the Fentanyl Era

(177) A Rapid Methadone Initiation Protocol for Stabilization of Opioid Withdrawal in the Fentanyl Era

Barriers to initiate buprenorphine and methadone for opioid use disorder treatment with postdischarge treatment linkage.

Hospitals are an essential site of care for people with opioid use disorder (OUD). Buprenorphine and methadone are underutilized in the hospital. Characterize barriers to in-hospital buprenorphine or methadone initiation to inform implementation strategies to increase OUD treatment provision. Survey of hospital-based clinicians' perceptions of OUD treatment from 12 hospitals conducted between June 2022 and August 2022. Survey questions were grouped into six domains: (1) evidence to treat OUD, (2) hospital processes to treat OUD, (3) buprenorphine or methadone initiation, (4) clinical practices to treat OUD, (5) leadership prioritization of OUD treatment, and (6) job satisfaction. Likert responses were dichotomized and associations between "readiness" to initiate buprenorphine or methadone and each domain were assessed. Of 160 respondents (60% response rate), 72 (45%) reported higher readiness to initiate buprenorphine compared to methadone, 55 (34%). Respondents with higher readiness to initiate medications for OUD were more likely to perceive that evidence supports the use of buprenorphine and methadone to treat OUD (p < .001), to perceive fewer barriers to treat OUD (p < .001), to incorporate OUD treatment into their clinical practice (p < .001), to perceive leadership support for OUD treatment (p < .007), and to have great job satisfaction (p < .04). Clinicians reported that OUD treatment protocols with treatment linkage, increased education, and addiction specialist support would facilitate OUD treatment provision. Interventions that incorporate protocols to initiate medications for OUD, include addiction specialist support and education, and ensure postdischarge OUD treatment linkage could facilitate hospital-based OUD treatment provision.

Rapid Methadone Induction in a General Hospital Setting: A Retrospective, Observational Analysis.

Outpatient methadone guidelines recommend starting at a low dose and titrating slowly. As fentanyl prevalence and opioid-related mortality increases, there is a need for individuals to rapidly achieve a therapeutic methadone dose. Hospitalization offers a monitored setting for methadone initiation, however dosing practices and safety are not well described. Retrospective, observational analysis of hospitalized patients with opioid use disorder seen by an inpatient addiction consult team in an academic medical center who were newly initiated on methadone between 2016 and 2022. We calculated initial daily dose, maximum daily dose, timing interval of dose escalation, whether patients were connected to an opioid treatment program (OTP) prior to discharge, whether adverse effects or safety events occurred during the hospitalization, and whether such events were definitely or probably related versus possibly related or unrelated to methadone. One hundred twelve patients were included. The mean initial daily methadone dose administered was 32 mg (range: 10-90 mg). The mean maximum dose reached was 76.8 mg (range 30-165 mg). The mean number of days from initial to peak dose was 5.6 days (range 1-19 days). Overall, 30% of patients experienced a safety event, most commonly sedation. Only 4 safety events were deemed probably or definitely related to methadone. In regression analyses, there was no significant difference between starting doses among patients with or without sedation but there was a relationship between last dose and the likelihood of any possibly related event, with those ending at a dose of 100 mg or higher having a higher likelihood event, compared to those ending at lower doses (47.8% vs 12.4%, P < .001). Seventy-six percent were connected to OTP before discharge. Among hospitalized patients initiating methadone, rapid dose titration was infrequently associated with related safety events and most were connected to community-based methadone treatment before discharge.

Identification of Factors Contributing to Methadone-Induced Daytime Sleepiness in Cancer Patients and Proposal of the Conversion Ratio from Other Opioids to Oral Methadone: A Retrospective Cohort Study.

When methadone is used to treat cancer pain, the Japanese health insurance system recommends to determine the starting dose according to the equivalency conversion table based on the morphine-equivalent daily dose (MEDD) of prior opioids proposed by the National Comprehensive Cancer Network. Owing to the wide range in variability of the conversion table, methadone increases the incidence of daytime sleepiness. To identify the factors associated with daytime sleepiness and propose a conversion ratio from pretreatment MEDD to oral methadone that decreases the risk of daytime sleepiness. Retrospective cohort study. One hundred patients who started oral methadone to relieve cancer pain at Ashiya Municipal Hospital (Hyogo, Japan) from January 1, 2013, to August 31, 2022, were enrolled. The primary endpoint, the conversion ratio from pretreatment MEDD to oral methadone without daytime sleepiness, was determined using receiver operator characteristic (ROC) curve analysis. The incidence of daytime sleepiness within seven days of methadone initiation was 40.0%. The factors identified as contributing to daytime sleepiness were pretreatment MEDD (odds ratio [OR]: 0.941, 95% confidence interval [CI]: 0.916-0.966, p <0.001) and methadone dose (OR: 1.395, 95% CI: 1.178-1.652, p <0.001). The conversion ratio from pretreatment MEDD to oral methadone was 0.24, with an area under the ROC curve of 0.909 (p <0.001). Daytime sleepiness developed when methadone dose is high relative to pretreatment MEDD. To the best of our knowledge, this is the first study to suggest the conversion ratio from pretreatment MEDD to oral methadone without causing daytime sleepiness.

Safety of rapid inpatient methadone initiation protocol: A retrospective cohort study

BackgroundCurrent methadone titration guidelines recommend low initial doses (15–40 mg) and slow increases (10–20 mg every 3 to 7 days) to prevent dose accumulation and oversedation until reaching a target therapeutic dose between 60 and 120 mg. These guidelines were created primarily for outpatient settings in the pre-fentanyl era. Methadone initiations are becoming more common in hospitals, but no titration guidelines exist specific to this treatment setting, which has capacity for increased monitoring. Our objective was to assess the safety of rapid inpatient methadone initiation with regard to mortality, overdose, and serious adverse outcomes both in-hospital and postdischarge. MethodsThis is a retrospective, observational, cohort study conducted at an urban, academic medical center in the United States. We queried our electronic medical record for hospitalized adults with moderate to severe opioid use disorder admitted between July 1, 2018, and November 30, 2021. Included patients were rapidly initiated on methadone with 30 mg as the initial dose and 10 mg increases daily until reaching 60 mg. The study extracted thirty-day post-discharge opioid overdose and mortality data from the CRISP database. ResultsTwenty-five hospitalized patients received rapid methadone initiation during the study period. The study had no major adverse events including in-hospital or thirty-day post-discharge overdoses or deaths. The study did have two instances of sedation, but neither led to methadone dose holds. There were no instances of QTc prolongation. The study had one patient-directed discharge. ConclusionsThis study demonstrated that a small subset of hospitalized patients tolerated rapid methadone initiation. More rapid titrations can be utilized in a monitored inpatient setting to retain patients in the hospital and allow providers to account for increased tolerance in the fentanyl era. Guidelines should be updated to reflect the capabilities of inpatient settings to safely initiate and rapidly titrate methadone. Further work should determine optimal methadone initiation protocols in the fentanyl era.