Modulation of Attentional Bias to Drug and Affective Cues by Therapeutic and Neuropsychological Factors in Patients With Opioid Use Disorder on Methadone Maintenance Therapy

Objective: Abnormal selective attention to drug cues and negative affect is observed in patients with substance dependence, and it is closely associated with drug addiction and relapse. Methadone maintenance is an effective replacement therapy to treat heroin addiction, which significantly reduces the relapse rate. The present study examines whether the patients with opioid use disorder on chronic methadone maintenance therapy exhibit abnormal attentional bias to drug cues and negative-affective cues. Moreover, its relation to therapeutic and neuropsychological factors is also examined.Methods: Seventy-nine patients with opioid use disorder under chronic methadone maintenance therapy and 73 age-, sex-, and education-matched healthy controls were recruited and assessed for attentional bias to drug cues and negative affect using a dot-probe detection task. Correlational analysis was used to examine the relationships between the attentional bias and the demographic, therapeutic, and neuropsychological factors.Results: No significant overall patient-control group difference is observed in drug-related or negative-affective-related attentional bias scores. In the patient group, however, a significant negative correlation is found between the attentional bias scores to negative-affective cues and the duration of methadone treatment (p = 0.027), with the patients receiving longer methadone treatment showing less attentional avoidance to negative-affective cues. A significant positive correlation is found between the negative affect-induced bias and the impulsivity score (p = 0.006), with more impulsive patients showing higher attentional avoidance to negative affective cues than less impulsive patients. Additionally, the patients detect a smaller percentage of probe stimuli following the drug (p = 0.029) or negative-affective pictures (p = 0.009) than the healthy controls.Conclusion: The results of the present study indicate that the patients under chronic methadone maintenance therapy show normalized attentional bias to drug and negative-affective cues, confirming the involuntary attention of the patients is not abnormally captured by external drug or negative-affective clues. Our findings also highlight that the attentional avoidance of negative-affective cues is modulated by the duration of methadone treatment and the impulsivity level in the patients.

Client satisfaction to methadone maintenance treatment program in Myanmar

Background To tackle the long-standing opioid misuse problem, Myanmar introduced the methadone maintenance treatment (MMT) program in 2006, starting with 260 clients. Since then, the program has been expanded across different geographical sites in the country. This study was done in 2017 to explore the treatment satisfaction of the clients towards the MMT program. Method A total of 210 clients with a minimum of six-month treatment history enrolled in five MMT program sites across Myanmar were recruited through stratified random sampling. Administering the Verona Service Satisfaction Scale for Methadone-Treatment (VSSS-MT), this study assessed the satisfactory responses under three categories viz., 1) clinic staff professional skills; 2) basic drug intervention; 3) specific intervention (individual rehabilitation and psychotherapy). Results The majority (89%, n = 186) of the respondents were satisfied with the current MMT program. Specifically, 89.5% (n = 187) were satisfied with the clinic staff professional skills category, 91.9% (n = 192) with the basic program intervention and 74.6% (n = 156) with specific interventions. Among the respondents, treatment satisfaction with the MMT program was higher (p < 0.05) in those (i) with a higher quality of life score in physical, psychological, social and environmental categories, ii) who were satisfied with their current marital and leisure status, and those iii) who consumed alcohol. Results from stepwise binary logistic regression showed alcohol consumption and physical health status had a significant association with MMT treatment satisfaction. Conclusion Treatment satisfaction of the clients, in general is high. However, the lower percentage of satisfied clients (74.6%) for the specific interventions category compared with 89.5 and 91.9% respectively for staff and basic drug management categories highlights the need for improvement in this category for overall enhancement of the MMT program.

Effect of Maternal Methadone Use on Neonatal Outcomes: Results of a Cohort Study

Background: Substance abuse treatment is challenging in pregnancy, and methadone maintenance therapy (MMT) is a therapeutic choice. Methadone can cross the placenta and is poorly secreted in breast milk. Given these inconsistent findings of methadone effect on neonatal outcomes, this study was done to investigate the results in neonates of mothers treated with methadone in Mashhad. Methods: In this retrospective cohort study, mothers referring to two academic hospitals of Mashhad University of Medical Sciences were studied. Three groups were considered: MMT, other drug abusers, and healthy control. Maternal information, including demographic characteristics, fertility characteristics, and methadone treatment-related characteristics, and neonatal information, including demographic characteristics and neonatal outcomes, were assessed. Results: Overall, 122 pregnant women with a mean age of 29.14 ± 4.44 years were studied in three groups: control (n = 59), MMT (n = 32), and other drug abusers (n = 31). Baseline characteristics (mothers’ age, residence, chronic hypertension, preeclampsia, diabetes, heart disease, thyroid disease, and other diseases) were not different between the three groups. The highest history of miscarriage was seen in other drug abusers (35.5%) (P = 0.023). The mean weight, height, and head circumference of neonates in the control group were significantly higher than the methadone group (P < 0.001), and in the methadone group was higher than in the other drugs abusers (P < 0.001). The highest prevalence of malformations (16.1%) and hospitalization in the NICU (51.6%) was observed in infants of other drug abusers. After adjusting for confounding variables, the odds ratio (OR) of low-birth-weight infants was 13.7 in the methadone group and 1946 in the other drugs group compared to the healthy control group. The OR of neonates less than 50cm in height was 11.4 in the methadone group and 22.5 in the other drugs. Besides, the OR of neonates less than 35cm was 4.7 in the methadone group and 7.3 in other drugs. Conclusions: Although the neonates of mothers who used methadone had a higher rate of inappropriate intrauterine growth indices than healthy women, methadone consumption compared to other drugs had significantly reduced unacceptable outcomes in neonates. Increased gestational age and reduced preterm delivery risk were observed in methadone-treated mothers.

Effect of Methadone Maintenance on Expression of BDNF and CREB Genes in Brain VTA of Male Morphine Treated Rats

Background: Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats Methods: I Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats Results: According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to significant reduction in the expression of BDNF and CREB genes at VTA as well as BDNF serum level compared with control group. Conclusion: It was concluded that methadone, like morphine, causes significant reduction in the expression of BDNF and CREB genes in brain VTA area of rat as well as BDNF serum level compared with control group.

Cost-Effectiveness and Guidelines for Opioid Substitution Treatment

There was evidence indicating that in the treatment of opioid use disorder, injectable hydromorphone, or injectable methadone provided more benefit at less cost compared with injectable diacetylmorphine over a 6-month time horizon. Evidence suggests that in the treatment of opioid use disorder, both injectable hydromorphone and injectable diacetylmorphine are likely to provide more benefit at less cost than methadone maintenance treatment. Treatment with injectable hydromorphone was more cost-effective than injectable diacetylmorphine in opioid use disorder patients who do not respond to or relapse from drug treatments. The evidence is limited because observed data were collected during a short-term follow-up, and long-term cost-effectiveness outcomes were based on extrapolations beyond data from the actual studies. One guideline provided a weak recommendation, supported by low-quality evidence, for using slow-release oral morphine in older adults with adequate renal function in whom buprenorphine and methadone maintenance have been ineffective to treat opioid use disorder or could not be tolerated. Another guideline recommends using injectable hydromorphone or injectable diacetylmorphine for individuals with severe opioid use disorders who relapsed previous treatments failed. No relevant cost-effectiveness evidence or guidelines with recommendations regarding the use of oral hydromorphone, fentanyl patches, or fentanyl buccal tablets for opioid use disorder treatment were identified; therefore, no summary can be provided.

Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences

Genetic variants in the OPRM1 and CYP2B6 genes, respectively coding for an opioid receptor and methadone metabolizers, have been linked to negative treatment outcomes in patients undergoing methadone maintenance treatment, with little consensus on their effect. This study aims to test the associations between pre-selected SNPs of OPRM1 and CYP2B6 and outcomes of continued opioid use, relapse, and methadone dose. It also aims to observe differences in associations within the sexes. 1,172 participants treated with methadone (nMale = 666, nFemale = 506) were included in this study. SNPs rs73568641 and rs7451325 from OPRM1 and all the tested CYP2B6 SNPs were detected to be in high linkage disequilibrium. Though no associations were found to be significant, noteworthy differences were observed in associations of OPRM1 rs73568641 and CYP2B6 rs3745274 with treatment outcomes between males and females. Further research is needed to determine if sex-specific differences are present.

Acupuncture for Opioid Dependence Patients Receiving Methadone Maintenance Treatment: A Network Meta-Analysis

Objectives: Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT.Methods: Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS).Results: A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (−8.59, 95% CI: −15.96 to −1.23, P &lt; 0.01), (−6.15, 95% CI: −9.45 to −2.85, P &lt; 0.05), and (−10.44, 95% CI: −16.11 to −4.77, P &lt; 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: −5.74, 95% CI: −11.60 to −0.10) on MHOWS. TEAS was more effective than WM (MD: −15.34, 95% CI: −27.34 to −3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence.Conclusions: The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.

Lapse and Relapse Rates in Narcotics Anonymous Versus Methadone Maintenance Treatment: A 12-Month Prospective Study

Objective: The present study aimed to compare lapse and relapse-free survival between patients treated in Narcotics Anonymous (NA) groups and Methadone Maintenance Treatment (MMT) centers and to determine the relationship between social support scale and treatment outcome. Method: This study was a prospective, 12-month cohort study using the random sampling method to select 100 newcomer patients treated by the NA Association as well as 100 patients in MMT centers. The data were collected using a demographic questionnaire and Social Support Appraisals (SSA) scale at the onset of the study along with follow-up phone calls every other week. Results: All participants were male, aged between 18 and 65 with a mean (SD) age of 38.98 (± 10.85) years. Prevalence of relapse in 12 months was 60.5%. The lapses in the MMT group and relapses in the NA group were significantly higher (P < 0.001). The younger patients with lower levels of education are at greater risk of lapse/relapse. The mean score of SSA was significantly higher in the MMT group than the NA group in all subscales, including friends, family, and the others' support (P < 0.001). The mean scores of SSA subscales for the participants without relapse in the NA group was significantly higher in comparison to the MMT group. Conclusion: Detection of factors related to drug abuse relapse/lapse may help addiction therapists to identify drug abuse patients with lapse/relapse and to develop treatment and policy guidelines to prevent relapse in addiction recovery.