Methadone Dose Research Articles

Association Between Variables and Transitions Among No Opioid Use, Opioid Use, and Subsequent Dropout Among Participants on Methadone Treatment: A Retrospective Study Utilizing a Multistate Model.

Although previous studies have reported the variables that influence opioid use or dropout among participants receiving methadone treatment, limited attention has been given to the variables related to transitions among no opioid use, opioid use, and dropout. This retrospective study utilized data collected from June 2010 to June 2022 at 11 methadone treatment clinics in Guangdong Province, China. Two transient states (no opioid use and opioid use) and 1 absorbing state (dropout) were defined based on monthly urine morphine test results and daily methadone intake records. We used a multistate model to explore the variables associated with transitions among no opioid use, opioid use, and dropout among participants. Among 3136 participants, with an average treatment duration of 497 days, 1646 (52.49%) underwent at least 1 period of opioid use, resulting in 3283 transitions from no opioid use to opioid use. The transitions between no opioid use and opioid use were significantly associated with variables such as age, gender, employment status, marital status, living situation, travel time to the clinic, human immunodeficiency virus and hepatitis C virus infection statuses, average methadone dosage, and attendance rates. The variables influencing participants' dropout varied depending on their opioid use behaviors. Additionally, the probability of a specified opioid use state remaining unchanged or transitioning to a different state at a defined time point would change over time. The opioid use behaviors of participants are dynamic. Methadone providers should offer targeted interventions based on participants' opioid use behaviors to effectively decrease rates of opioid use and improve retention.

Substance use patterns and negative urine opioid screen among patients on methadone treatment at a referral hospital in Nairobi, Kenya

Background Substance use is a global health concern, with opioids contributing significantly to the disease burden. In Kenya, Medically Assisted Therapy (MAT) programs using methadone have been implemented to address opioid use disorder. Despite the effectiveness of methadone, the concurrent use of other substances remains a critical challenge. This study aimed to assess substance use patterns at enrolment and evaluate the prevalence of negative urine opioid screens among patients attending a MAT clinic at a tertiary hospital in Kenya. Methods This retrospective cohort study analyzed data from the medical records of 713 patients enrolled in the MAT clinic between December 2014 and February 2018. Data on sociodemographic characteristics, concurrent substance use at enrolment, and urine opioid screen results at 6, 12, 18, and 24 months were collected. Multivariate analyses were performed to identify factors associated with concurrent substance use, and the likelihood of achieving negative urine opioid screens. Results At enrolment into the MAT program, nearly all participants (712 out of 713) reported concurrent use of additional substances, with tobacco (91%) and cannabis (82.9%) being the most common. Concurrent substance use was significantly influenced by participants age, gender, education level, and route of administration of the substance. The program achieved an 81.3% retention rate at 24 months. However, the prevalence of negative urine opioid screens was lower compared to other populations, with a gradual increase from 61.3% at 6 months to 81.4% at 24 months. Notably, male patients (HR = 1.411, 95% C.I. 1.063–1.873, p = 0.01700) and those receiving higher methadone doses (HR 7.052, 95% CI 3.408–14.593, p<0.0001) were more likely to achieve negative urine opioid screens. Conclusions This study reveals a high prevalence of concurrent substance use among patients enrolling in the MAT program in Kenya, which may affect their likelihood of achieving negative urine opioid screens. These findings underscore the need for methadone treatment programs to adopt comprehensive approaches that address all substance use disorders to improve treatment outcomes.

Low-dose methadone added to another opioid for cancer pain: a multicentre prospective study

ContextThe use of methadone for cancer pain management is gaining wider acceptance. However, switching to methadone treatment can still pose challenges. Consequently, there is ongoing development of its use in low doses in combination with other opioids, despite a lack of clinical evidence regarding its efficacy and safety.ObjectivesThis study aimed to evaluate the efficacy and tolerability of low-dose methadone in combination with another opioid in patients with moderate-to-severe cancer-related pain in a clinical setting.Patients and methodsThis was a prospective, open-label study conducted in 19 pain and/or palliative care centres treating patients with cancer-related pain. Pain intensity, patients' global impression of change, and adverse effects were assessed on day 7 and day 14. The main outcome measure was the proportion of responders.ResultsThe study included 92 patients. The daily dose of methadone was 3 [3–6] mg at baseline, 9 [4–10] mg on day 7 and 10 [6–15] mg on day 14. The NRS pain ratings significantly decreased from 7 [6–8] at baseline to 5 [3–6] on visit 2 (p < .0001) and 4 [3–6] on visit 3 (p < .0001). Similarly, the VRS pain ratings decreased from 3 [3–3] at baseline to 2 [2–3] on visit 2 (p = 0.026) and 2 [1–3] (p < 0.001) on visit 3. At Visits 1 and 2, half of the patients were considered Responders. Of those responders, 73.5% were High-Responders at Visit 1 and 58.7% were High-Responders at Visit 2. No adverse events related to the risk of QT prolongation, overdose, or drug interactions were reported.ConclusionFor patients experiencing moderate to severe cancer-related pain despite initial opioid treatment, our study found that low-dose methadone, when used in combination with another opioid, was both safe and effective. This supports the use of methadone as an adjunct to opioid-based treatment for cancer pain.

8798 How Low Can You Go: Suspected Methadone-Induced Hyperinsulinemia

Abstract Disclosure: L. Ravindra: None. M.G. Fernandez: None. V. Cheng: None. Background: Studies have shown that methadone use can result in severe hypoglycemia. This is thought to be related to methadone having antagonistic activity at NMDA receptors, resulting in increased pancreatic insulin release, suppressed glucagon and epinephrine, and inhibition of hepatic glycogenolysis. These mechanisms affect the normal physiologic response to hypoglycemia and can result in hyperinsulinemic-induced hypoglycemia. Clinical case: We present a case of a 56-year-old male with complex regional pain syndrome managed with a high daily dose of methadone (345 mg) who presented to the hospital for evaluation of failure to thrive and hypoglycemia. During the hospital admission, evaluation of hypoglycemia included a serum blood glucose level of 41 mg/dL (normal &amp;gt;60 mg/dL), with an inappropriately normal level of insulin 10 (Reference Range (RR) 3-25 mU/L), C-peptide 2.9 (RR 0.5-3.3 ng/ml), Pro-insulin 2.9 (RR 3-20 pmol/L), an undetectable level of Beta-hydroxybutyrate &amp;lt;0.10 (RR 0.02-0.27 mMol/L) negative insulin antibodies &amp;lt;0.4 (RR 0.0 - 0.4 U/mL), and negative sulfonylurea screen. Additional labs included a normal TSH of 2.8 (RR 0.3-5.5 mIU/ml) and appropriate morning cortisol of 23 (RR &amp;gt;14-15 μg/dL). The abdominal CT and follow-up MRI did not reveal any definite abnormalities in the pancreas. Given persistent evidence of hyperinsulinemic-induced hypoglycemia, a PET Dotatate scan was performed, confirming the absence of a neuroendocrine tumor. While admitted, management included nutritional optimization, close glucose monitoring, and an intravenous dextrose infusion. Diazoxide was also initiated and gradually increased to 150 mg three times a day. Addiction Medicine assisted in tapering down the methadone dose from 115 mg to 105 mg three times a day. With these interventions, the patient had no further episodes of hypoglycemia. On discharge, the patient was provided with a continuous glucose monitor. On follow-up, the patient has continued to show improvement and the diazoxide dose has been decreased without recurrent hypoglycemia. Given this, a selective arterial calcium stimulation test was not pursued. Conclusion: Methadone is an uncommon cause of hyperinsulinemic-induced hypoglycemia. Suspicion should arise, particularly in patients on high doses. Current evidence suggests tapering methadone dosage as the primary intervention, as insulin levels can decrease drastically and improve hypoglycemia. This therapeutic approach should be considered before pursuing invasive and costly diagnostic testing. Presentation: 6/3/2024

Sedative effects of intramuscular alfaxalone–methadone–midazolam versus ketamine–methadone–midazolam in cats

ObjectiveTo assess depth and quality of sedation and the ability to place an intravenous catheter in cats after intramuscular (IM) injection with alfaxalone–methadone–midazolam (AMM) or ketamine–methadone–midazolam (KMM). Study designBlinded randomized clinical trial. AnimalsA group of 46 healthy Domestic Short Hair cats. MethodsCats were randomly assigned to be administered IM methadone 0.3 mg kg–1 and midazolam 0.3 mg kg–1 with either alfaxalone 2 mg kg–1 (AMM group, n = 23) or ketamine 3 mg kg–1 (KMM group, n = 23). Before IM injection, a temperament score was assigned. The reaction to injection was scored. After 15 minutes, the depth of sedation was scored using a simple descriptive scale (SDS) and multidimensional sedation score. Success or failure to place an intravenous catheter at first attempt was recorded; p < 0.05. ResultsCats in the AMM group had a significantly higher median temperament score (p = 0.026). Behavioural reaction to injection with AMM was significantly less compared with KMM (p = 0.016). Median sedation scores were significantly higher in the AMM group than in the KMM group: SDS 4 (0–4) versus 2 (0–4), p = 0.01, respectively; multidimensional sedation score AMM 13 (0–13) versus 3 (0–10), indicating superior sedative effect in the AMM group, p = 0.01. Success rate of catheter placement was significantly higher in the AMM group (18/23) than in the KMM group (10/23), p = 0.033. Conclusionsand clinical relevance Addition of 2 mg kg–1 alfaxalone to 0.3 mg kg–1 methadone and 0.3 mg kg–1 midazolam provided better sedation after IM injection than ketamine 3 mg kg–1 combined with the same doses of methadone and midazolam. This combination of drugs may be particularly desirable as an alternative to α-2 adrenoceptor agonist-based protocols for cats requiring IM sedation.

Variation in Opioid Agonist Dosing in Clinical Trials by Race and Ethnicity

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials. This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. Combined race and ethnicity as self-classified by the patient at trial enrollment. The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥16 mg and methadone ≥60 mg) were compared across race and ethnicity groups. A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥16 mg; methadone ≥60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients. In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

The effect of intraoperative methadone on postoperative opioid requirements in children undergoing orchiopexy: A randomized clinical trial

AbstractBackgroundChildren undergoing outpatient surgery are at risk of inadequate postoperative pain control. Methadone has a long duration of action and an intraoperative dose may provide stable analgesia throughout the postoperative period. Intraoperative methadone has been shown to improve pain control in adolescents but its use for postoperative pain in pediatric patients undergoing outpatient surgery has not been studied before. Therefore, we conducted a double‐blind randomized placebo‐controlled trial to investigate the effects of a single dose of intraoperative methadone in children aged less than 5 years undergoing orchiopexy for undescended testis.MethodsA total of 68 children were randomized to receive either methadone (0.1 mg/kg) or isotonic saline following induction of anesthesia. Exclusion criteria included preterm birth, previous scrotal surgery, and parents' inability to consent. Primary outcomes were opioid requirements (first primary outcome) and pain intensity in the post‐anesthesia care unit. Secondary outcomes included episodes of desaturation and time until readiness to discharge from the post‐anesthesia care unit, sleep on the first postoperative night, pain intensity, and opioid requirements at home until the evening on the first postoperative day. Follow‐up was 4 days.ResultsSixty children completed the study (age, mean ± SD, 26.2 ± 13.9 months), 29 children received methadone, and 31 children received placebo. Eighteen children required opioids in the post‐anesthesia care unit, five children in the methadone group (proportion = 0.17, 95% confidence interval (CI): 0.07, 0.36) compared to thirteen patients in the placebo group (0.42, 95% CI: 0.26, 0.60) (mean difference = −0.24 and 95% CI: −0.03, −0.47) (p = 0.037). Five children in the methadone group (0.17, 95% CI: 0.03, 0.31) versus ten in the placebo group (0.32, 95% CI: 0.16, 0.49) had a face, legs, activity, cry, consolability score of ≥5 in the post‐anesthesia care unit (mean difference = −0.15, 95% CI: −0.36, 0.06) (p = .179). More children in the placebo group woke up due to pain the first night following surgery (seven children vs. one child). The methadone group had a longer stay in the post‐anesthesia care unit. There were no differences between the two groups regarding the other secondary outcomes.ConclusionA single dose of intraoperative methadone reduces short‐term postoperative opioid requirements in children after orchiopexy for nondescended testes but prolongs the duration of their stay in the post‐anesthesia care unit.

Alternative Reinforcers Enhance the Effects of Opioid Antagonists, but Not Agonists, on Oxycodone Choice Self-Administration in Nonhuman Primates.

Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration-approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032-1.0 mg/kg), nalbuphine (0.32-10 mg/kg), buprenorphine (0.0032-0.032 mg/kg), methadone (0.32-1.0 mg/kg), or flumazenil (1-3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a μ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy μ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy μ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse-related behaviors. SIGNIFICANCE STATEMENT: Clinical treatment programs for opioid use disorder use a combination of pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective have not been fully characterized. This study examined whether the effectiveness of μ-opioid medications to decrease oxycodone self-administration is altered in the presence of an alternative reinforcer. The results suggest that alternative reinforcers enhance the effects of antagonist or low-efficacy partial agonists, suggesting they may be a more effective strategy to curtail opioid use.

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.

Impact of chronic opioid on cognitive function and spermatogenesis in rat: An experimental study.

Opioid analgesics like morphine and methadone are widely used for managing severe pain; however, concerns over their potential misuse and adverse effects on the brain and reproductive system are significant. We aimed to investigate their impacts on spermatogenesis and cognitive function in male Norway rats. In this experimental study, 36 male Norway rats (250-300 gr, 6 months old) were divided into 6 groups: low-dose morphine, high-dose morphine, low-dose methadone, high-dose methadone, positive control (received normal saline at 5 mg/kg), and negative control (received no treatment). Morphine and methadone were administered intraperitoneally over 30 days at doses of 3 mg/kg and 7 mg/kg, respectively. Behavioral assessments evaluated anxiety, stress, and short- and long-term memory. Sperm parameters (viability, motility, morphology), hormonal analysis (testosterone, luteinizing hormone, follicle-stimulating hormone, estradiol), and gene expressions (Tp53, CatSper1) were assessed. A significant reduction in rat weight was observed in the high-dose morphine group (p = 0.0045), while testicular weights remained unchanged. Sperm abnormalities were observed with high doses of methadone and morphine. High-dose methadone significantly reduced offspring count (p = 0.0004). Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol varied significantly across treatment groups. Gene expression was altered in response to treatments (p 0.05). Prolonged exposure to methadone and morphine resulted in memory dysfunction, chronic stress, hormonal disturbances, altered gene expression, and fertility complications. These effects were more pronounced at higher doses, highlighting the importance of careful dosage management in opioid therapy.

Use of a quadratus lumborum block in queens undergoing ovariectomy: a randomised controlled trial.

The aim of the study was to evaluate the perioperative analgesic effect of a quadratus lumborum (QL) block in queens undergoing ovariectomy. A total of 37 healthy queens admitted for elective ovariectomy were randomised into two groups: control (CTRL, n = 19) and QL block (QL, n = 18). All cats were premedicated with dexmedetomidine 0.005 mg/kg, alfaxalone 1 mg/kg and methadone 0.1 mg/kg IM. Under general anaesthesia, cats allocated to the QL group received a bilateral ultrasound-guided QL block with 0.4 ml/kg of ropivacaine 0.4% (3.2 mg/kg). No treatment was administered to cats in the CTRL group. Intraoperative rescue fentanyl boluses were administered if haemodynamic and/or respiratory parameters exceeded 30% of the pre-incisional values. Postoperative methadone boluses were administered based on Feline Grimace Scale scores. Demographics, baseline vital parameter values, requirement for rescue analgesia, incidence of hypotension, sialorrhoea, vomiting and dysphoria, and number of cats accepting food at 6 h after extubation were compared between groups. A higher number of queens required intraoperative fentanyl in the CTRL group (14/18, 77.8%) compared with the QL group (1/19, 5.3%) (P <0.001). The median total fentanyl dose was 4 µg/kg (range 0-4) in the CTRL group and 0 µg/kg (range 0-4) in the QL group (P <0.001). No statistically significant difference was found between groups when comparing the number of animals requiring postoperative methadone, total methadone dose, episodes of hypotension, sialorrhoea, vomiting and dysphoria, and number of queens accepting food at 6 h postoperatively. No adverse effect or complication potentially related to the block was recorded. The QL block resulted in a lower intraoperative fentanyl requirement in queens undergoing ovariectomy. Further studies are needed to clarify the postoperative analgesic effect of this technique in cats.

Characteristics of women on opioid substitution therapy in primary healthcare in Tshwane (South Africa): a retrospective observational study.

Women who use drugs face specific challenges compared to men, such as higher rates of HIV infection, unsafe injecting practices and intimate partner violence. However, this population's access to drug dependence treatment and gender-sensitive interventions remains limited, leading to unmet needs and increased vulnerability. To investigate the characteristics of and associations with retention in care among women on opioid substitution therapy (OST) in a community based primary care setting. A descriptive observational study within the Community Orientated Substance Use Programme in Tshwane, South Africa. Data from 199 women (>18 years) on OST was extracted from an electronic database and paper-based files. Data was analysed descriptively, and inferential analysis looked for association of variables with retention on OST for≥6 months. Majority of participants were unemployed, with 44.3% falling within the 20-29 years age range. During the initiation and course of OST, 39.2% of women experienced intimate partner violence, and 19.0% were pregnant. Retention on OST was significantly associated with increasing age at initiation (p=0.047), knowledge of HIV status (p=0.029), an increase in the ASSIST score (p=0.023), and methadone dose (p<0.001). Factors such as race, employment status, health system level, pregnancy, intimate partner using substances, intimate partner violence, route of administering opioids, and having tuberculosis and/or hepatitis C exposure did not show a significant relationship with retention on OST (p>0.05). This study reveals specific vulnerabilities in women receiving OST, emphasising the need for the integration of interventions to address reproductive health, violence mitigation, infectious disease and polydrug use into care.

Erectile dysfunction among male patients receiving methadone maintenance treatment: focusing on anxiety-related symptoms.

Erectile dysfunction (ED) in patients receiving methadone maintenance treatment (MMT) is a relatively neglected issue. In this study we sought to determine the actual prevalence of ED and risky sexual behaviors in patients receiving MMT and identify clinically relevant risk factors for ED, particularly mental health conditions, that may contribute to achieving holistic healthcare and improving treatment adherence in this patient population. A cross-sectional study of male Chinese MMT patients was conducted. Comprehensive demographic and clinical data regarding age, obesity, history of major mental and physical illness, HIV infection, other substance use, methadone dose/duration, and associated risky sexual behaviors were all collected. Assessment tools, including the 5-item International Index of Erectile Function, the Chinese Health Questionnaire, and the Taiwanese Depression Questionnaire were administered. The relationship between mental health-related factors and ED was fully analyzed and elaborated. The prevalence of ED among male patients in a methadone maintenance therapy outpatient clinic was 55.7%. The prevalence rate of ED among the individuals treated for longer than 6months was 56.8%, whereas that for untreated individuals was 52.0%. Additionally, methadone-treated individuals were older and had a higher proportion of condom use and drug-assisted sexual activity than untreated individuals. Pearson correlation revealed that higher Chinese Health Questionnaire and Taiwanese Depression Questionnaire scores were negatively correlated with lower scores on the 5-item International Index of Erectile Function. In the multivariate regression model, anxiety and other psychosomatic symptoms were associated with more severe ED, whereas individuals who consumed alcohol within the past month had less severe ED after adjustment for other demographic and clinical variables. The findings of the present study revealed no association between ED and methadone treatment duration or dosage. Healthcare professionals should discuss mental health issues in patients on MMT with ED, especially anxiety symptoms and recent alcohol use. This study is one of the few reports within the limited body of research highlighting a significant association of ED with anxiety-related symptoms in patients undergoing MMT. Our study had some limitations. First, the sample size of HIV-infected individuals was insufficient. Second, the cross-sectional study design could not definitively demonstrate a causal mechanism. In patients undergoing MMT, individuals who reported less severe anxiety symptoms and alcohol consumption in the past month tended to have less severe ED, regardless of the MMT duration or dosage.

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.

W68 - Greater Coupling of Pain Intensity and Opioid Craving After Delaying Methadone Dose Among Veterans With Opioid Use Disorder

W68 - Greater Coupling of Pain Intensity and Opioid Craving After Delaying Methadone Dose Among Veterans With Opioid Use Disorder

Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). 6 MMT clinics in China. Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. Acupuncture or sham acupuncture 3 times a week for 8 weeks. The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. National Natural Science Foundation of China.

Treatment non-adherence among methadone maintenance patients and associated factors: a multicenter, cross-sectional study in Vietnam

ObjectiveThis multicenter, cross-sectional study was conducted to investigate the prevalence of treatment non-adherence and its associated factors among methadone maintenance patients in Vietnam.MethodsThis secondary data analysis was conducted using the data from a previous study. Six hundred patients were interviewed face-to-face to collect data on their demographic characteristics and social support. Information about the treatment characteristics and patients’ non-adherence was gathered from medical records and books monitoring their treatment process. Treatment non-adherence was defined as missing at least one methadone dose in the last three months.ResultsThe overall prevalence of non-adherence was 45.7%. The average social support score of patients who completely adhered to treatment was significantly higher than that of those who did not (p < 0.001). In the multivariate logistic regression model, for each one-unit increase in social support (one score), treatment time (a year), and patient’s monthly income (one million Vietnam dongs), the odds of non-adherence decreased by 28% (aOR = 0.72, 95%CI 0.59–0.88, p = 0.002), 15% (aOR = 0.85, 95%CI 0.80–0.91, p < 0.001) and 9% (aOR = 0.91, 95%CI 0.85–0.97, p = 0.004), respectively. Patients living in Son La (a mountainous province) were 1.72 times (95%CI 1.09–2.71) more likely to be non-adherent as compared to those in other areas (p = 0.020). As per univariate analyses, other associated factors could be age, education level, family monthly income, occupation, and opioid relapse (p < 0.001).ConclusionsA high non-adherence rate was found among Vietnamese methadone maintenance patients. Interventions involving social support, occupation, income, and education are needed to improve their treatment adherence.

A preliminary investigation of the acute effects of delta-9-tetrahydrocannabinol on pain and opioid attentional bias among persons with opioid use disorder

IntroductionAttentional bias (AB) is believed to be an important factor in the development and maintenance of both opioid use disorder (OUD) and chronic pain. Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), produce analgesic effects via processes that are potentially relevant to AB and is commonly used by persons with OUD. This exploratory study investigated if THC influences AB towards pain and opioid cues individuals with OUD. MethodsUsing a within-subject, crossover design, 27 adults receiving methadone were randomly assigned to receive single doses of oral THC (10 mg, 20 mg administered as dronabinol) or placebo across three, 5-h sessions. During each session, a visual probe task was used to measure AB to pain and opioid cues at baseline and 120 min post-THC administration. ResultsMixed-effects models examined main effects of THC dose, time, and their interaction across all participants; findings were then stratified by methadone dose (low dose <90 mg/day and high dose ≥90 mg/day). Among individuals receiving high doses of methadone, a significant interaction was observed such that AB towards opioids increased following 10 mg THC administration and decreased following 20 mg THC administration. Additionally, participants receiving low doses of methadone showed significant increases in the variability of opioid-related AB post THC administration. ConclusionWe provide preliminary evidence showing that THC may cause dose-dependent effects on selective attention for opioid cues among methadone patients. These results underscore the need for further clinical investigation into the effects of cannabinoids and other substances with potential analgesic and addictive properties among persons with OUD.

Standard Versus Rapid Inpatient Methadone Titration for Pregnant Patients With Opioid Use Disorder: A Retrospective Cohort Study.

Our study evaluated if rapid inpatient titration of methadone for pregnant patients with opioid use disorder (OUD) improved outcomes without increasing the risk for overdose. This is a retrospective cohort study of pregnant patients admitted for inpatient methadone titration from January 2020 to June 2022. Outcomes were compared between standard versus rapid titration protocols. Standard titration involved an initial methadone dose with additional doses every 6 hours if clinical opiate withdrawal score (COWS) is >9. Rapid titration involved an initial methadone dose with additional doses every 4 hours if COWS is >9. The primary outcome was time required to achieve stable dose. Secondary outcomes included elopement prior to achieving stable dose, methadone-related readmission, opioid overdose, and final dose. There were 97 patients in the standard titration (STP) and 97 patients in the rapid titration (RTP) groups. Demographic characteristics and substance use history did not differ between the 2 groups. Time to stable dose did not differ between the 2 groups (RTP, 5.0 days ±4.0; STP, 4.0 days ±3.0; P = 0.08). Patients in the rapid titration group were less likely to elope from the hospital prior to stabilization (RTP 23.0% vs STP 37.9%, P = 0.03) and had fewer methadone-related readmissions (P < 0.001). One patient (1.0%) in the RTP group required naloxone treatment while inpatient for concern for overdose, while none did in the STP group (P = 0.32). There was no difference in median final stable dose between the 2 groups (P = 0.07). Rapid titration of methadone for pregnant patients with OUD was associated with decreased medical elopement and methadone-related readmission, without increasing the risk for overdose.

Impact of baseline methamphetamine/amphetamine use on discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder in Canada.

Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription-type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada. Secondary analysis of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation). Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60-3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32-3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p > .05). This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population.