Benefits and challenges experienced by participants on long-term methadone maintenance treatment in China: a qualitative study.

BACKGROUND: Methadone maintenance treatment (MMT) has been implemented in China for nearly two decades, with a significant decrease in the number of participants in recent years. However, there is a lack of comprehensive research focusing on the long-term effectiveness in the context of this decline, especially from the perspectives of MMT participants themselves. This study aims to address this gap by examining the benefits and challenges experienced by long-term MMT participants in China, to uncover potential causes of the decrease in participant numbers and to improve the effectiveness of the program. METHODS: We conducted semi-structured interviews with 21 long-term MMT participants (treatment duration ≥ 5 years) recruited through purposive sampling from 6 MMT clinics in the Guangdong Province, China, between December 2021 and August 2022. Thematic analysis was employed to analyze the transcribed interviews. Two analysts independently coded the data, and a third researcher double-coded 20% of transcripts to ensure intercoder reliability. RESULTS: Overall, participants corroborated the notable decline in MMT participants during their long-term MMT, citing death, arrest, and self-perceived abstinence from heroin, as their perceived driving factors. They reported positive changes in their health, family relationships, and social functioning. However, they identified economic hardship as their greatest challenge associated with MMT, further exacerbated by other barriers including the conflict of clinic opening hours and working schedules, discrimination from employers, and COVID-19-related restrictions. Additionally, participants identified issues with dose adjustment and emergency treatment continuation. CONCLUSIONS: This study outlines the overall improvement in the quality of life of long-term MMT participants. However, it highlights the need for official guidelines for dose adjustment and emergency treatment continuation as well as the provision of health education, job referrals, and flexibility of clinic opening times to facilitate the return to society receiving participants. Establishing a follow-up mechanism for those receiving MMT is also recommended to prevent relapses to heroin and other illicit substances.

CYP2B6 and ABCB1 genotypes predict methadone plasma exposure among patients on maintenance therapy against opioid addictions in Tanzania.

AIMS: Methadone maintenance therapy (MMT) exhibits significant variability in pharmacokinetics and clinical response, partly due to genetic variations. However, data from sub-Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid-addicted Tanzanian patients. METHODS: Patients attending MMT clinics (n = 119) in Tanzania were genotyped for common functional variants of the CYP3A4, CYP3A5, CYP2A6, CYP2B6, CYP2C19, CYP2D6, ABCB1, UGT2B7 and SLCO1B1 genotypes. Trough plasma concentrations of total methadone, S-methadone (S-MTD) and R-methadone (R-MTD), with their respective metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The methadone-to-EDDP metabolic ratio (MMR) was used to categorize the phenotype. RESULTS: The proportions of MMR-predicted ultrarapid, extensive, intermediate and slow methadone metabolizer phenotypes were 2.5%, 58.2%, 23.7% and 15.6%, respectively. CYP2B6 genotype significantly correlated with S-methadone (P = .006), total methadone (P = .03), and dose-normalized methadone plasma concentrations (P = .001). Metabolic ratios of R-methadone (R-MTD/R-EDDP), S-methadone (S-MTD/S-EDDP), and total methadone (MMR) were significantly higher among patients homozygous for defective variants (*6 or *18) than heterozygous or CYP2B6*1/*1 genotypes (P < .001). The metabolic ratio for S-MTD and total methadone was significantly higher among ABCB1c.3435T/T than in the C/C genotype. No significant effect of CYP2D6, CYP2C19, CYP3A4, CYP3A5, CYP2A6, UGT2B7 and SLCO1B1 genotypes on S-methadone, R-methadone, or total methadone was observed. CONCLUSIONS: Approximately one in six opioid-addicted Tanzanian patients are methadone slow metabolizers, influenced by genetic factors. Both the CYP2B6 and ABCB1 genotypes are strong predictors of methadone metabolic capacity and plasma exposure. Further investigation is needed to determine their predictive value for methadone treatment outcomes and to develop genotype-based dosing algorithms for safe and effective therapy.

DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment.

BACKGROUND: Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). METHODS: 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. RESULTS: Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. CONCLUSION: DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.

A randomized controlled trial on the effect of cranial electrotherapy stimulation on depression, anxiety, and craving in addicted male patients undergoing methadone maintenance treatment.

BACKGROUND: Addicted patients undergoing methadone maintenance treatment are prone to several complications and the risk of relapse. OBJECTIVE: The present study aims to investigate the effect of cranial electrotherapy stimulation on depression, anxiety, and craving in addicted male people undergoing methadone maintenance treatment. METHODS: This randomized controlled trial study was conducted on 60 male patients referred to Persia addiction treatment center between 2021 and 2022. Patients were randomly divided into two equal treatment and placebo groups. The treatment group received cranial electrotherapy stimulation intervention for 48 sessions of 30 min. Depression and anxiety were evaluated using the Hamilton questionnaire before and after the intervention, and the level of craving was also evaluated with the Federdi 2008 questionnaire. RESULTS: Comparing the level of depression and anxiety before and after the intervention in both treatment and placebo groups did not show any significant difference (p < 0.05). Craving after the intervention was significantly different in both groups and was lower in the treatment group compared to the placebo group (33.43 versus 42.17, p = 0.004). In the placebo group, the level of anxiety and depression, and in the treatment group, the level of depression, anxiety and craving for consumption decreased significantly after the intervention compared to before the intervention (p < 0.05). CONCLUSION: Cranial electrotherapy stimulation did not have a significant effect on reducing the level of depression and anxiety of patients, but it is effective in the reduction of craving in addicted people undergoing methadone maintenance treatment. TRIAL REGISTRATION: This randomized clinical trial was registered on 2022/5/13 with clinical trial code of IRCT20210523051367N1.

Outcome in methadone maintenance treatment of immigrants from the former Union of Soviet Socialist Republics.

CONTEXT: Immigrants from the former Union of Soviet Socialist Republics (USSR) are more prevalent in Methadone maintenance treatment (MMT) in Israel than their percentage in the general population. AIMS: To compare their characteristics and outcomes to those of Israeli-born and other immigrant patients. METHODS: Retention and survival since admission (June/1993-Dec/2022) until leaving treatment (for retention), or at the end of follow-up were analyzed. Vital data was taken from a national registry. Predictors were estimated using Kaplan-Meier and Cox regression models. RESULTS: The USSR patients (N = 262) compared with other immigrants (N = 132) and Israeli-born (N = 696) were more educated (≥ 12y) (p < 0.001), admitted to MMT at a younger age (p < 0.001), following a shorter duration of opioid usage (p < 0.001). More of them ever injected drugs (p < 0.001) and ever drank alcohol (p < 0.001). One-year retention was comparable (77.2% vs. 75.6% and 72%, p = 0.2) as did opioid discontinuation in those who stayed (p = 0.2). Former USSR patients had longer cumulative retention of their first admission (p = 0.05) with comparable overall retention since first admission, and survival, although the age of death was younger. Specific origin within the former USSR found immigrants from the Russian Federation with the best outcome, and those from Ukraine as having high HIV seropositive and shorter retention. CONCLUSIONS: Despite several characteristics known to be associated with poor outcomes, former USSR immigrants showed better adherence to MMT, reflected by their longer cumulative retention in their first admission, lower rate of readmissions, and a comparable survival and overall retention in treatment. An in depth study is needed in order to understand why they decease at a younger age.

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

OBJECTIVE: This multicenter, cross-sectional study was conducted to investigate the prevalence of treatment non-adherence and its associated factors among methadone maintenance patients in Vietnam. METHODS: This 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. RESULTS: The 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). CONCLUSIONS: A 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.

Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment.

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of µ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.

Relapse risk revealed by degree centrality and cluster analysis in heroin addicts undergoing methadone maintenance treatment.

BACKGROUND: Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis. METHODS: Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse. RESULTS: Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical-striatal-thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse. CONCLUSION: MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.

Reduced mortality in patients with extended duration of methadone maintenance treatment: a five-year retrospective nationwide study.

BACKGROUND: The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration. METHODS: A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012-2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1-364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve. RESULTS: The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60-0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury. CONCLUSIONS: Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

The Role of Adverse Childhood Experiences on People in Opiate Agonist Treatment: The Importance of Feeling Unloved.

INTRODUCTION: Adults in opiate agonist treatment (OAT) often have a background of adverse childhood experiences (ACEs) and are more likely to be exposed to a variety of risks that may trigger post-traumatic stress disorder (PTSD). Summative ACE scores are often used to identify individuals at risk of PTSD and continued substance use. What has not been addressed is whether specific ACE factors are exerting a greater influence on the individual. This study investigated whether specific ACEs predicted PTSD, and current continued substance use among adults in long-term OAT. METHODS: An analysis of data that were collected at the follow-up stage of a study among 131 adults who attended OAT was conducted. Participants attended one of six OAT settings, covering 45% (n = 890) of clients in a defined area of Dublin, Ireland in 2017. Interviews were conducted with 104 participants, 66 males (63%) and 38 females (37%), with an average age of 43 years (SD = 7.4). The Adverse Childhood Questionnaire (ACQ); PTSD checklist (PCL-5); heroin; tranquilliser; cannabis; alcohol; and cocaine used in the previous 28 days were measured using the quantity used score within the Opiate Treatment Index. Socio-demographics and age of first use of these four substances were also collected. The analysis has focussed on relating ACEs to PTSD, age of first drugs use, and current drug use of the participants. RESULTS: Bivariate analysis showed that the summative ACQ score was significantly correlated with age of first opiate use (p = 0.004). Multiple regression analysis showed that the summative ACQ score and tranquilliser use predicted higher levels of PTSD (R2 = 0.50). Four specific ACEs predicted 54% of the variance in PTSD, these were feeling unloved (ß = 0.328) living with a household member who had a problem with alcohol or used illicit street drugs (ß = 0.280); verbal abuse (ß = 0.219); and living with a person who had a mental illness (ß = 0.197). CONCLUSIONS: While a summation of all ten ACEs predicted higher levels of PTSD, the factor "feeling unloved" as a child provided the single strongest predictor and may represent an overarching risk of PTSD and continued substance use in later life among adults in treatment for an opiate use disorder.

The rising threat of illicit amphetamine-type stimulant use among methadone maintenance treatment patients in East Coast Malaysia: a retrospective observational study.

Background: In recent years, amphetamine-type-stimulants (ATS) have been extensively misused in South-East Asia, inducing major problems among methadone-maintenance-treatment (MMT) patients.Objective: We examine ATS-misuse prevalence and its determinants among MMT patients in East-Coast-Malaysia.Methods: A retrospective-observational study was conducted on government-subsidized medication for opioid-use-disorder (MOUD) treatment clinics involving 292 MMT-patients (98% males) who were selected using a multilevel-proportional-stratified random sampling technique. Information obtained during the mandatory monitoring procedure from January 1 to December 31 2019, was utilized to determine ATS misuse prevalence from consecutive random urine drug screening. The determinants associated with its use, namely sociodemographics, social networks, comorbidities, and pharmacological assessments were analyzed via a logistic model.Results: Overall, 52.2% of the MMT-patients (95% CI: 0.42-0.54) had misused ATS at least once during their methadone treatment. These misusing patients were active smokers, hepatitis B and C seronegative, concurrently misused opioids, and had received suboptimum prescribed doses of methadone. Multiple logistic regression analysis demonstrated that the odds of misusing ATS during methadone treatment were 37 times higher among those who concurrently misused opioids (AOR: 37.60, 95% CI: 14.03-100.74) and 12 times higher among those who received suboptimal methadone doses (<60 mg/day) (AOR: 12.24, 95% CI: 5.58-25.43).Conclusion: This study demonstrated the significant prevalence of ATS misuse among MMT-patients in East-Coast-Malaysia, especially among patients who were prescribed suboptimal doses of methadone and/or demonstrated concomitant opioid-misuse. Stringent urine-monitoring is crucial to prevent diversion to ATS misuse. Nonetheless, to avoid negligence and improve physician engagement, the relevant authorities should immediately plan a comprehensive national-standard training module comprising support activities for professional methadone-prescribers.

Opioid relapse and its predictors among methadone maintenance patients: a multicenter, cross-sectional study in Vietnam.

BACKGROUND: Opioid relapse, one of the common and severe problems during methadone maintenance treatment, can give rise to poor treatment outcomes. This study measured the opioid relapse rate and its associated factors among methadone maintenance patients in Vietnam. METHODS: Information about the demographic characteristics and social support of 655 patients was collected through direct interviews. Medical records were used to gather data on treatment characteristics. Relapse was determined via urine opioid test results. RESULTS: The overall relapse rate of patients during treatment was 13.1%. According to the multivariate logistic regression model, living in mountainous areas (adjusted odds ratio (aOR) = 3.63, 95% CI 1.90-7.46) and long duration of drug use in the past (aOR = 1.06, 95% CI 1.03-1.09) were associated with an increase in the odds of opioid relapse. By contrast, living with many family members (aOR = 0.69, 95% CI 0.55-0.85), having longer treatment time (aOR = 0.80, 95% CI 0.73-0.87), and completely adhering to treatment (aOR = 0.38, 95% CI 0.23-0.64) were protective for opioid relapse. As per the univariate analyses, the odds of opioid relapse declined by 25% for each increase of one close friend or relative (OR = 0.75, 95% CI 0.66-0.86). Regarding social support (range score: 0-100), each additional increase of one score was associated with a 1% decrease in the odds of opioid relapse (OR = 0.99, 95% CI 0.98-0.99). Patient sex, education level, occupation type, patient's monthly income, family's monthly income, the number of previous treatments, daily methadone dose, comorbidity, and received antiretroviral therapy were not associated with opioid relapse among patients (p > 0.05). CONCLUSIONS: Residence, the role of family and social support, and treatment adherence should be paid more attention to guarantee and enhance the success of methadone maintenance treatment.

The effect of multivitamins on anxiety and depression in patients undergoing methadone maintenance treatment: A double-blind randomized controlled trial.

BACKGROUND: The prevalence of addiction is increasing in the world. Methadone Maintenance Treatment (MMT) can be associated with severe stress and mild to moderate depressive symptoms. Vitamins and minerals are commonly found in multivitamins seem to improve mood. Therefore, the aim of this study was to evaluate the effect of multivitamins on anxiety and depression in patients undergoing MMT in a double-blind randomized controlled trial. METHODS: The study was designed as a double-blind, randomized controlled trial and involved 70 male MMT patients over the age of 18. Participants were randomized to one of two groups, either those receiving multivitamins or those receiving a placebo for 12 weeks. The multivitamin capsule included vitamin E, B1, B2, B3, B5, B6, B12, C, biotin, folic acid, and zinc. Anxiety and depression were measured using standard questionnaires, before and after the intervention. RESULTS: The between-group comparison (i.e., intervention vs. placebo) indicated there was no significant difference in anxiety scores; however, there was a significant between-group difference in depression scores, favoring the intervention group. CONCLUSIONS: Multivitamin supplementation improved depression but did not have a significant impact on anxiety in patients undergoing MMT.

Stigma experienced by people living with HIV who are on methadone maintenance treatment and have symptoms of common mental disorders in Hanoi, Vietnam: a qualitative study.

BACKGROUND: Stigma around human immunodeficiency virus (HIV), injection drug use (IDU), and mental health disorders can be co-occurring and have different impacts on the well-being of people living with HIV (PWH) who use drugs and have mental health disorders. This stigma can come from society, health professionals, and internalized stigma. A person who has more than one health condition can experience overlapping health-related stigma and levels of stigma which can prevent them from receiving necessary support and healthcare, serving to intensify their experience with stigma. This study investigates HIV, drug use, and mental health stigmas in three dimensions (social, internalized, and professional) around PWH on methadone maintenance treatment (MMT) who have common mental disorders (CMDs) including depression, anxiety, and stress-related disorders in Hanoi, Vietnam.Please check and confirm whether corresponding author's email id is correctly identified.The cooresponding author's email is correct METHODS: We conducted semi-structured, in-depth interviews (IDIs) (n = 21) and two focus group discussions (FGDs) (n = 10) with PWH receiving MMT who have CMD symptoms, their family members, clinic health care providers, and clinic directors. We applied thematic analysis using NVIVO software version 12.0, with themes based on IDI and FGD guides and emergent themes from interview transcripts. RESULTS: The study found evidence of different stigmas towards HIV, IDU, and CMDs from the community, family, health care providers, and participants themselves. Community and family members were physically and emotionally distant from patients due to societal stigma around illicit drug use and fears of acquiring HIV. Participants often conflated stigmas around drug use and HIV, referring to these stigmas interchangeably. The internalized stigma around having HIV and injecting drugs made PWH on MMT hesitant to seek support for CMDs. These stigmas compounded to negatively impact participants' health. CONCLUSIONS: Strategies to reduce stigma affecting PWH on MMT should concurrently address stigmas around HIV, drug addiction, and mental health. Future studies could explore approaches to address internalized stigma to improve self-esteem, mental health, and capacities to cope with stigma for PWH on MMT. TRIAL REGISTRATION: NCT04790201, available at clinicaltrials.gov.

Different outcomes of methadone maintenance therapy in rehabilitated and relapsed drug addicts: significance of liver and renal biomarkers.

Methadone eliminates heroin use, reduces death rates and criminality associated with heroin use, and improves patients' health and social productivity. This study included long-term addicts who completed a methadone therapy program as well as relapsed patients. Liver and renal markers important for methadone metabolism were analyzed. Renal markers included urea and creatinine, while hepatic markers included total bilirubin, AST, ALT, γGT, and LDH as nonspecific but significant parameters of liver metabolism. The study included 34 male and 6 female heroin-dependent patients undergoing a rehabilitation program with methadone maintenance treatment (MMT). During therapy, average values ​​of all parameters remained within the reference interval but individual parameters in some patients were very high. Significant differences for urea (0.00) and very high individual variations in all parameters, especially γGT and LDH, were found in patients who were in relapse. Age of the patients did not show a correlation with the presence of significant differences in serum biochemical parameters during therapy. Prolonged use of methadone therapy stabilizes high variations of liver and renal markers. MMT achieves a stabilization of serum indicators relevant for methadone metabolism that correlates with the duration of consumption and the type of opioid substance. The most important hepato-renal markers as indicators of therapy success are γGT, LDH, and creatinine. The validity of former enzymatic tests (AST, ALP, and ALT) should be seriously reconsidered in terms of MTT treatment success and monitoring the health of heroin addicts.

Identifying the Physical and Mental Healthcare Needs of Opioid Treatment Program Clients.

Background: Individuals with opioid use disorder (OUD) often have significant medical and behavioral health needs that are unaddressed. Opioid treatment programs (OTP) are uniquely positioned to provide integrated services for OUD, physical and mental health but are underutilized for this purpose. This study aims to describe the physical and mental healthcare needs of OTP clients in order to inform integrated care implementation in OTPs. Method: OTP clients (n = 1261) in an integrated care program in the Bronx borough of New York City were assessed for mental health symptoms (e.g., anxiety, depression), chronic disease indicators (e.g., blood pressure, cholesterol), and general functioning (e.g., capability of managing healthcare needs). Results: Symptoms of anxiety, post-traumatic stress, and depression were common. Self-reported health status and level of functioning were generally poor. Heavy smoking and obesity were the most frequent physical health risks. Other chronic disease indicators (e.g., blood pressure) showed 25-46% may be at risk. Sixty percent had multiple mental health risks and 85% had multiple physical health risks. Older clients had a higher rate of hypertension and diabetes risk than younger clients. Conclusions: Integrated care programs in OTPs must be prepared to address and coordinate care for chronic mental and physical health conditions in addition to OUD.

Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment.

Chronic opioid use disorder patients often also use other substances such as amphetamines. The gene-based analysis method was applied in the genomic database obtained from our previous study with 343 methadone maintenance treatment (MMT) patients. We found that the gene encoding gamma-aminobutyric acid type A receptors (GABA-A receptor) delta subunit isoforms (GABRD) was associated with amphetamine use in heroin dependent patients under MMT in Taiwan. A total of 15% of the 343 MMT patients tested positive for amphetamine in the urine toxicology test. Two genetic variants in the GABRD, rs2889475 and rs2376805, were found to be associated with the positive urine amphetamine test. They are located in the exon 1 of the splice variant and altered amino acid compositions (T126I, C/T, for rs2889475, and R252Q, G/A, for rs2376805). The CC genotype carriers of rs2889475 showed a four times higher risk of amphetamine use than those with TT genotype. The GG genotype carriers of rs2376805 showed a three times higher risk of amphetamine use than the AA genotype carriers. To our knowledge, this is the first report that demonstrated an association of the delta splice variant isoform in the GABA-A receptor with an increased risk of amphetamine use in MMT patients. Our results suggest that rs2889475 and rs2376805 may be indicators for the functional role and risk of amphetamine use in MMT patients.

Use of Pre-exposure Prophylaxis Among People Who Inject Drugs: Exploratory Findings of the Interaction Between Race, Homelessness, and Trust.

Scale-up of pre-exposure prophylaxis (PrEP) in people who inject drugs (PWID) remains suboptimal. Patient-level factors are often complex and may contribute to scale-up. Using cross-sectional data from 234 opioid-dependent patients on methadone who met eligibility criteria for PrEP, we conducted logistic regression analyses to assess potential moderators associated with being on PrEP (n = 60). Mean provider trust was significantly higher among Blacks vs Whites (39.4 vs 34.9; p = 0.002) and non-homeless vs homeless participants (37.5 vs 34.8; p = 0.008). Though race/ethnicity was not a significant moderator on provider trust and PrEP use, increased provider trust was marginally associated with increased PrEP use among Blacks (p = 0.058). Additionally, homelessness significantly moderated provider trust and PrEP use (p = 0.024). Provider trust among non-homeless participants was positively correlated with PrEP use (p = 0.013) but not among homeless participants. Strategies that promote provider trust in Blacks and non-homeless PWID on methadone may improve PrEP scale-up.

Thrombosis of the Renal Vein and Inferior Vena Cava Associated With Placental Fetal Vascular Malperfusion in a Neonate Exposed to Methadone Maintenance Therapy In Utero.

Methadone, an opioid agonist, is the recommended treatment for pregnant women with opioid use disorder (OUD). Fetal/neonatal autopsy findings as well as placental changes in the setting of maternal OUD or methadone maintenance therapy (MMT) are not well-characterized. Here we present a case of a neonate who had exposure to MMT while in utero and died shortly after birth and was subsequently found to have multifocal calcified renal vein thrombosis, a recent inferior vena cava thrombus, and placental features of fetal vascular malperfusion at autopsy.

Polymorphisms in Stress-Related Genes Are Associated with Reduced Cocaine Abuse and Longer Retention in Methadone Maintenance Treatment for Opioid Use Disorder.

BACKGROUND: As CRH-binding protein (CRHBP) SNP rs1500 was associated with reduced cocaine abuse after 1 year in methadone maintenance treatment (MMT) for heroin addiction, we evaluated the association of additional 28 selected SNPs, in 17 stress-related genes, with MMT outcome. METHODS: The distribution of genotypes of each SNP by cocaine abuse after 1 year in MMT was assessed under the dominant and recessive models using χ2. Cumulative retention (up to 26.5 years) was studied using Kaplan-Meier analyses. Logistic regression and Cox model were used for multivariate analyses. RESULTS: Of a nonselective sample of 404 patients, 25 patients with <50% Europeans/Middle Eastern ancestry were excluded. Of the remaining 379 patients, 330 (87.1%) stayed at least 1 year in treatment. Four SNPs were associated with cocaine abuse after 1 year in MMT. A lower proportion of cocaine abusers was found in the groups of subjects with the following genotypes: arginine vasopressin (AVP) SNP rs2282018 CC, CRHBP rs7728378 TT, galanin rs3136541 TT/TC, and neuropeptide Y receptor Y1 (NPY1R) rs4518200 AA. The following independent variables were associated with lack of cocaine in urine after 1 year (multivariate analyses): CRHBP rs7728378 TT, NPY1R rs4518200 AA, no cocaine in urine on admission, as well as opiate and benzodiazepine use after 1 year in MMT. Cumulative retention (n = 379) was longer in carriers of AVP rs2282018 CC (13.7 years, 95% CI 11.1-16.2) versus TT/TC genotypes (10.5, 95% CI 9.4-11.5) (p = 0.0230) Conclusions: The study suggests that a reduction in cocaine abuse and longer retention among MMT patients is mediated in part by variants in stress-related genes and is a step toward precision medicine.