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.

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.

Factors affecting addiction severity index (ASI) among clients enrolled in methadone maintenance treatment (MMT) program in Myanmar.

BACKGROUND: Opioid substitution with methadone maintenance treatment (MMT) is shown to reduce illicit opioid use and renew social functioning. Understanding factors that undermine clients' social functioning during MMT treatment is vital for improving treatment compliance and quality of life. METHOD: A total of 210 respondents who were already enrolled in a formal MMT program in Myanmar were recruited from five cities through stratified random sampling for this cross-sectional study. The addiction severity index (ASI) was used to objectively assess respondents social functioning in the last 30 days. Higher ASI scores denote poorer social functioning. RESULT: Respondents total ASI scores in the respective domains were: employment (47.4%), alcohol (44.4%), drug use (7.2%), legal (49.2%) and social-family relationship (10.7%). Those reported to have never injected drugs in the last 30 days had lower ASI total scores than those who reported injection drug use (p = 0.01). After identifying the differences in ASI total scores, we found there were significant associations in the clients' hepatitis C status, age category, frequency of heroin injection, quality of life score, marital status, current leisure status with family/friend, current history of injection in the last 30 days, income status, satisfaction with current marital status, as well as reported drug and alcohol use (p < 0.05). Stepwise binary logistic regression showed that alcohol and higher frequency of heroin injection were associated with higher ASI scores. Meanwhile, older age, respondents those who had leisure time with family, and satisfied with current marital status had lower ASI scores (p < 0.05). CONCLUSION: Our results indicate that those enrolled in the MMT program in Myanmar faced many challenges in their daily social functioning. Treatment providers must take heed of these apparent impediment to ensure clients chequered social functioning does not undermine their treatment compliance. TRIAL REGISTRATION: NA.

Commune Health Workers' Methadone Maintenance Treatment (MMT) Knowledge and Perceived Difficulties Providing Decentralized MMT Services in Vietnam.

BACKGROUND: With the initial establishment of countrywide methadone maintenance therapy (MMT) system, Vietnam is in the process of expanding and decentralizing the MMT program to community-based healthcare settings. OBJECTIVE: The study aimed to measure the MMT-related knowledge and perceived difficulties in treating patient who use drugs (PWUD) among community-based healthcare providers, e.g., commune health workers (CHW), and examine its correlated factors. METHODS: A total of 300 CHW from 60 communes in two provinces of Vietnam completed a survey using Audio Computer-Assisted Self-Interview (ACASI) method. Twelve true-or-false questions were used to assess the CHW's MMT-related knowledge. The CHW's background characteristics and perceived difficulties treating PWUD were recorded. RESULTS: The mean MMT knowledge score was 8.2 (SD = 1.2; range: 5-11). Misconceptions toward the benefits, procedure, and side effects of MMT were prevalent. The participants perceived varying degrees of difficulties in recruiting, engaging, and communicating with PWUD. With all covariates holding constant, younger age (standardized ẞ = -0.166; p = 0.0078) was associated with less MMT-related knowledge. Number of PWUD seen in a month and MMT-related knowledge was associated with less perceived difficulties treating PWUD. Conclusions/importance: The finding shed lights on the CHW's knowledge gap, which need to be addressed to facilitate the decentralization of MMT services in Vietnam. In preparation for a decentralized MMT service delivery model, specially designed training is warranted to equip CHW with knowledge and confidence to provide MMT-related services to PWUD.

High prevalence of willingness to use direct-acting antiviral-based regimens for hepatitis C virus (HCV) infection among HIV/HCV coinfected people who use drugs.

OBJECTIVES: Despite the high burden of hepatitis C virus (HCV)-related morbidity and mortality among HIV-positive people who use illicit drugs (PWUD), uptake of interferon-based treatments for HCV infection has been negligible among this group. Direct-acting antiviral (DAA) therapies offer an opportunity to expand treatment access among this population. The aim of this study was to explore willingness to use DAA-based regimens among HIV/HCV-coinfected PWUD in Vancouver, Canada. METHODS: Data were drawn from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), a prospective cohort of HIV-positive PWUD. Using logistic regression analyses, we investigated factors associated with willingness to use DAA-based regimens among HIV/HCV-coinfected participants. RESULTS: Of 418 HIV/HCV-coinfected PWUD surveyed between June 2014 and May 2015, 295 (71%) were willing to use DAA-based regimens. In multivariable analysis, participants enrolled in methadone maintenance therapy [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.04-2.51], those with a recent assessment by an HCV specialist (AOR 2.02; 95% CI 1.28-3.19) and those who perceived that HCV infection was affecting their health (AOR 2.49; 95% CI 1.41-4.37) were more likely to be willing to use DAA-based regimens. CONCLUSIONS: Overall, this study found a high prevalence of willingness to use DAA-based regimens among HIV/HCV-coinfected PWUD in Vancouver. Importantly, enrolment in methadone maintenance therapy was positively associated with willingness, suggesting that integrated models of HIV, HCV and addiction care should be explored as a way to address HCV-related morbidity and mortality among HIV/HCV-coinfected PWUD.

Retrospective analysis of antiretroviral therapy uptake and retention of male clients receiving methadone maintenance therapy in two provinces in Vietnam: potential synergy of the two therapies.

BACKGROUND: Vietnam has a concentrated HIV epidemic with injection drug use being the dominant mode of HIV transmission. Vietnam has rapidly expanded antiretroviral therapy (ART) and methadone maintenance therapy (MMT). This study aims to analyze ART uptake and retention among male clients receiving MMT in Vietnam in the early phase of the MMT program. METHODS: The male clients (age ≥18) who were newly enrolled in care or started ART at two HIV clinics in Hanoi (2009 to 2011) and three HIV clinics in Can Tho (2010 to 2012) were included for the analysis. The CD4 lymphocyte count at HIV care enrollment and ART initiation and retention on ART were retrospectively analyzed. The values of those receiving MMT were compared with the values of two groups: those in whom injection drug use (IDU) status was documented, but were not receiving MMT, and all male clients not receiving MMT. To analyze retention, survival analysis with log rank test and Cox proportional hazard model was used. RESULTS: During the study period, 663 adult men were newly enrolled in HIV care (237 had IDU status documented) and 456 initiated ART (167 had IDU status documented). Among those who initiated ART, 28 were receiving MMT. At care enrolment, those receiving MMT had a median CD4 count of 230 (IQR 57-308) cells/mm3, while men self-reporting IDU and not receiving MMT and all men not receiving MMT had a median CD4 count of 158 (IQR 50-370) cells/mm3 and 143 (IQR 35-366) cells/mm3, respectively. At ART initiation, men receiving MMT had significantly higher CD4 count with median at 203 (IQR 64-290) cells/mm3 than men self-reporting IDU and not receiving MMT (80, IQR 40-220, cells/mm3, p = 0.038) and all men not receiving MMT (76, IQR 20-199, cells/mm3, p = 0.009). Those receiving MMT had a significantly higher retention rate than those self-reporting IDU but not receiving MMT (hazard ratio = 0.18, p = 0.019) and men not receiving MMT (hazard ratio = 0.20, p = 0.041). CONCLUSIONS: Our analysis suggests that men receiving MMT in Vietnam are achieving relatively early uptake and high retention rates on ART. The findings support potential benefits of integrating MMT and ART services in Vietnam.

Barriers to retention in methadone maintenance therapy among people who inject drugs in Bangkok, Thailand: a mixed-methods study.

BACKGROUND: Methadone maintenance therapy (MMT) is a mainstay for treating opioid use disorder and preventing and managing HIV among people who inject drugs (PWID). While previous research suggested low dosing of methadone and high rates of discontinuation of MMT among PWID in Thailand, little is known about patients' lived experiences with MMT in this setting. Therefore, we conducted a mixed-methods study to examine barriers to retention in MMT among PWID in Bangkok, Thailand, with particular attention to methadone dosing. METHODS: Bivariate statistics were used to analyze quantitative survey data collected from methadone-treated PWID between July and October 2011. Qualitative data collected through semi-structured interviews with 16 methadone-treated PWID between July 2011 and June 2012 were analyzed thematically, with a focus on individual-level, social-structural, and environmental barriers to accessing MMT. RESULTS: Among 158 survey participants, a median dosage of methadone was 30 mg/day (interquartile range 20-50). Of these, 15.8% reported having acquired street methadone due to low prescribed dosages of methadone and 19.0% reported recent syringe sharing. Qualitative interview data indicated some methadone provider-related barriers, including discouraging patients from using methadone due to it being a Western medicine, difficulty negotiating higher doses of methadone, and abrupt dose reductions without patient consultation (involving the provision of non-medicated "syrup" in some cases). Social-structural and environmental barriers to optimal MMT access included intense police surveillance of methadone clinics; and frequent incarceration of PWID and a lack of access to methadone in prisons. CONCLUSIONS: Among our sample of methadone-treated PWID, methadone dosages were suboptimal according to the international guidelines. Poor adherence to international guidelines for opioid agonist therapies, aggressive law enforcement, and a lack of methadone in prisons need to be addressed to optimize MMT and reduce harms associated with untreated opioid use disorder in Thailand.

Client Acceptability for Integrating Antiretroviral Therapy in Methadone Maintenance Therapy Clinics in Sichuan, China.

BACKGROUND: Using methadone maintenance therapy (MMT) clinics to deliver antiretroviral therapy (ART) has proven to be effective for promoting treatment initiation and adherence in drug users living with HIV. OBJECTIVES: The objective of this study was to investigate the HIV-positive client acceptability of integrated ART services and to identify the reasons for and factors associated with service acceptability. METHODS: A total of 86 HIV-positive MMT clients were recruited from 12 MMT clinics in Sichuan Province, China. They participated in a cross-sectional survey that queried their willingness to receive seven different types of MMT-based ART services. The reasons for their willingness/unwillingness to accept these services were documented. The association between service acceptability and background characteristics was examined. RESULTS: The most accepted integrated services were ART-related counseling (75.6%) and referral (73.2%). Concerns regarding the provider's lack of ART expertise and confidentiality issues were common barriers for the acceptance of MMT-based ART services. A trust relationship with MMT providers was a reason for service acceptance. Service acceptability was associated with a poorer perceived health status. Conclusions/Importance: ART-related services, based on the client perspective, can be delivered at MMT clinics. However, service provider training and the protection of confidentiality must be strengthened for the effective implementation of integrated service delivery.

Comparison Between Urinalysis Results and Self-Reported Heroin Use Among Patients Undergoing Methadone Maintenance Treatment in China.

BACKGROUND: The validity and concordance of two main measures of drug use behavior, self-report and urinalysis, has long been discussed. More understanding is needed about the underlying factors associated with discordance between these two methods. OBJECTIVES: Describe the pattern and associated factors of discordance between self-reported heroin use and the urinalysis results of opiate use among methadone maintenance therapy (MMT) patients in China. METHODS: A total of 2,448 MMT patients from 68 clinics in five provinces of China participated in a survey, which collected information on demographics, drug use and MMT-related factors, depressive symptoms, and drug avoidance self-efficacy. The most recent urine morphine test result was obtained from medical records and compared with self-reported heroin use. Participants who had urinalysis within 14 days of the survey were included in the analysis. RESULTS: Among the 1,092 participants, 70 (6.4%) self-reported heroin use and 195 (17.9%) had positive urinalysis results. The over-reporters group had significantly higher education, and the under-reporters had significantly higher level of drug-avoidance self-efficacy and lower level of depressive symptoms. Among the participants who either self-reported heroin use or had positive urinalysis results, being young, having higher education, and having lower level of depressive symptoms were associated with discordance between self-reports and urinalysis results. CONCLUSION: The combination of both measures in assessing drug use behavior seems necessary. The validity of self-report should be considered differently based on demographic and psychosocial characteristics.

Why People Who Inject Drugs Voluntarily Transition Off Methadone in Ukraine.

Methadone maintenance therapy (MMT) treats opioid use disorder among people who inject drugs (PWID). To understand why PWID may voluntarily discontinue MMT, we analyzed data from 25 focus groups conducted in five Ukrainian cities from February to April 2013 with 199 participants who were currently, previously, or never on MMT. Using constant comparison method, we uncovered three themes explaining why PWID transition off MMT: (a) purposeful resistance to rigid social control associated with how MMT is delivered and to power asymmetries in provider-patient relationships, (b) self-management of a PWID's "wounded identity" that is common in socially stigmatized and physically sick persons-MMT serves as a reminder of their illness, and (c) the quest for a "normal life" uninterrupted by daily MMT site visits, harassment, and time inefficiencies, resources, and social capital. Focusing on holistic principles of recovery would improve addiction treatment and HIV prevention in Ukraine and globally.

Experiences of substance abusers from methadone maintenance therapy.

Background: Substance abusers are not able to withdraw drugs eternally despite the abundance of different treatments; therefore, withdrawal programs are not quite successful and notwithstanding all the successes of methadone maintenance therapy, there are some defects found in the manner this treatment is applied. Thus, this study was conducted to explore the experience of drug abusers regarding methadone maintenance therapy. Methods: This is a qualitative study using content analysis methodology. The research community includes drug abusers admitted to the treatment centers of the western cities of Mazandaran Province, Iran in 2016. The sampling was purposive and the data were collected by face-to-face single interviews with 20 patients. The interviews were continued up to data saturation. Finally, the Lundman and Grenheim method was used to analyze the interviews and the four criteria of Guba and Lincoln were applied to check data integrity. Results: "Buying time," "methadone dependence," and "looking from a narrow view to the patient" were the main three categories that fit the results. Conclusion: Governmental free services for drug abusers; paying attention to different aspects of treatment such as mental, emotional, and social recovery; lifelong support of the family and society members; and balance in prescribing and following the treatment process prescribed by health care providers can enhance both the quality and safety of the treatment process. Psychological consultation alongside social services can facilitate the recovery process in methadone maintenance therapy.

Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT).

BACKGROUND: Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Large interindividual variability in serum methadone levels for therapeutic response has been reported. Genetic variations in ABCB1 gene may be responsible for the variability in observed methadone concentrations. OBJECTIVE: This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT). METHODS: One hundred and forty-eight male opioid-dependent patients receiving MMT were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from whole blood and genotyped for ABCB1 polymorphisms [i.e. 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642)] using the allelic discrimination real-time polymerase chain reaction (PCR). Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the dose. Serum methadone concentrations were measured using the Methadone ELISA Kit. RESULTS: Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval. Patients with CGC/TTT diplotype had 32.9% higher dose-adjusted serum methadone concentration over the 24-hour dosing interval when compared with those without the diplotype [mean (SD) = 8.12 (0.84) and 6.11 (0.41) ng ml-1 mg-1, respectively; p = 0.033]. CONCLUSION: There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT. Genotyping of ABCB1 among opioid-dependent patients on MMT may help individualize and optimize methadone substitution treatment.

A placebo-controlled trial of dextromethorphan as an adjunct in opioid-dependent patients undergoing methadone maintenance treatment.

BACKGROUND: Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). METHODS: Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-ß1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. RESULTS: After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. CONCLUSIONS: We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT.

Psychosocial combined with methadone maintenance treatments versus methadone maintenance treatments alone for treatment of opioid use disorder: A meta-analysis.

BACKGROUND: Psychosocial combined with methadone maintenance treatment aimed at opioid use disorder is effective, but the efficacy of the psychosocial intervention in such treatment is questionable. OBJECTIVES: This study aims to evaluate the effectiveness of psychosocial plus methadone maintenance treatment versus methadone maintenance treatment alone for opioid use disorder in improving treatment retention and reducing drug use. METHODS: An exhaustive literature search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure database, "the Wan Fang database, the VIP database, and the Chinese Biomedical Literature Database", and randomized controlled trials were identified from their inception to February 2021. RESULTS: Twenty-four studies were included. The results of this meta-analysis showed that adding any psychosocial treatment to standard methadone maintenance treatment significantly improved the illicit drug use during the treatment relative risk (RR) 0.62 (95% CI 0.48 to 0.79), and retention in treatment RR 1.18 (95% CI 1.11 to 1.25). No statistically significant additional benefit was detected in terms of retention at follow-up RR 1.08 (95% CI 0.95 to 1.22). CONCLUSIONS: The present evidence suggests that adding psychosocial intervention to methadone maintenance treatment significantly improves the nonuse of opioids and retention in treatment. It should be noted that psychosocial treatment is only beneficial for methadone treatment when methadone is provided in subtherapeutic doses. Additionally, the finding about the improvement effect of retention at follow-up did not achieve statistical significance. Due to the diversity of outcome indicators in relevant original studies, the included studies are limited.

Impact of combination of intermittent theta burst stimulation and methadone maintenance treatment in individuals with opioid use disorder: A comparative study.

Prior studies indicate that subjects undergoing methadone maintenance therapy (MMT) may experience anxiety, depression and cravings. This study aimed to explore the impact of intermittent theta burst stimulation (iTBS)-MMT combination on craving and emotional symptoms of opioid use disorder. This comparative study included subjects with opioid use disorder at the Methadone Maintenance Clinic of Pudong New Area between September 2019 and March 2020. The subjects were divided into two groups: those who received iTBS-MMT combination treatment (iTBS-MMT) and those who received MMT treatment and sham stimulation treatment (MMT). Outcomes were reduction rate of anxiety, depression and craving. Anxiety was measured by Hamilton Anxiety (HAMA) scale, depression was determined by Hamilton Depression (HAMD) scale and craving was analyzed using visual analog scale. A total of 76 subjects completed the treatment, with 38 subjects in each group. Twenty days after treatment, subjects in the iTBS-MMT group had significant improvement of anxiety (HAMA reduction rate), depression (HAMD reduction rate) and craving (Craving reduction rate) reduction rate compared with MMT group. iTBS-MMT combination treatment may produce better drug craving reduction and emotional improvement than MMT alone.

The Prevalence and Psychosocial Correlates of Ketum (Mitragyna speciosa) Use among Individuals on Methadone Maintenance Therapy Programme in Hospital Taiping, Malaysia.

Ketum use is significantly prevalent amongst individuals in the northern states of Peninsular Malaysia. This study aims to investigate the prevalence and psychosocial correlates of Ketum use in individuals who are in the Methadone Maintenance Therapy (MMT) Programme at the Hospital Taiping. This is a cross-sectional study conducted in the methadone clinic at the Hospital Taiping. The study instruments used were Subjective Opiate Withdrawal Scale (SOWS), Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) questionnaire, and Kratom Dependence Scale (KDS). A total of 215 subjects were recruited for this study. The prevalence of ketum users was 49.3% (n = 106). Chinese and Indian ethnicity had a lower tendency to use ketum compared to Malay ethnicity, with OR = 0.386 (95% CI 0.134, 1.113) and 0.119 (95% CI 0.035, 0.408), respectively. Individuals who used other illicit drugs had a higher tendency to use ketum with the adjusted OR = 9.914 (95% CI: 1.109, 88.602). Every one unit increase in SOWS increased the odds of being a ketum user by 1.340 (95% CI: 1.070, 1.677), whereas every one unit increase in duration in the MMT programme reduced the odds of being a ketum user by 0.990 (95% CI: 0.982, 0.998). Ketum use is prevalent amongst those in the MMT programme in this study. The high prevalence of ketum use is of concern and further interventions should be carried out to address this.

Comparing the Effects of Melatonin and Zolpidem on Mental Health and Sexual Function in Men With Opioid Addiction: Evidence From a Randomized Clinical Trial.

Background: Mental health problems and impaired sexual function are widely reported among those suffering from drug abuse, particularly among those under methadone maintenance therapy (MMT). Aims: The current study aimed to, firstly, investigate the effect of melatonin and zolpidem on mental health and sexual function of those with drug abuse under MMT, and, secondly, to compare the effects of melatonin and zolpidem on the studied outcomes. Methods: The current randomized, single-blind, placebo-controlled clinical trial was conducted on 98 participants who were randomly assigned into three groups of melatonin (n = 34), zolpidem (n = 32), and placebo (n = 32). All participants received the intervention once a day for 30 days, without changes in nutrition. Mental health and sexual function were measured before and 30 days after the intervention. Results: The mean age of participants in the groups of melatonin, zolpidem, and placebo was 35.8 ± 9.6 years (22-58 years of old), 35.9 ± 9.3 years (21-58), and 37.2 ± 7.8 years (26-53), respectively. Sexual function mean score was significantly increased from 38 to 41 in the melatonin group, while it deceased in zolpidem (from 39.1 to 38) and placebo (39.25-38.59) groups. Also, mental health mean scores improved statistically significantly in the melatonin group (from 60.65 to 43.56; p = 0.002), and descriptively in the zolpidem group (57.88-51.18; p = 0.129). Concerning both outcomes, the observed improvement was considerably higher in the melatonin group. The highest improvement was observed in dimensions of overall satisfaction and depression in the melatonin group (1.18 and -8.4, respectively). Conclusion: Melatonin could significantly improve both mental health and some domains of sexual function of those with drug abuse under MMT, while zolpidem did not show a significant effect. Trial Registration Number: https://www.irct.ir/trial/53047, identifier: IRCT20201214049718N1.

Pregabalin Toxicity-Induced Posterior Reversible Encephalopathy Syndrome.

Pregabalin, a prescription medication typically used for neuropathic pain, has increasingly been overused and abused. We present a unique case of a 51-year-old woman with a history of polysubstance use disorder and on methadone therapy who presented to the emergency department with altered mental status after consuming an unknown supratherapeutic amount of pregabalin. She was stabilized and discharged. Within 24 hours, she ingested another 1000mg of pregabalin, presenting again with altered mental status, along with tachycardia and hypertension. Computed tomography (CT) without contrast and fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) revealed subcortical white matter edema in the bilateral frontal and occipital lobes as well as the left parietal lobe, suggestive of posterior reversible encephalopathy syndrome (PRES). The patient recovered after four days of supportive treatment with an antihypertensive and an antiepileptic. PRES is a neurological phenomenon in which vasogenic edema, most commonly accumulating in the posterior parieto-occipital white matter, causes headaches, altered mental status, and seizures. To our knowledge, there has not been an established link between pregabalin toxicity and PRES, and the awareness of this potential complication can help in the early diagnosis and management of the disease to prevent further progression.

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.

Experiences of Clients in Three Types of Methadone Maintenance Therapy in an Atlantic Canadian City: A Qualitative Study.

BACKGROUND: Methadone maintenance therapy remains the most common form of substitution therapy for opioid use disorder in Canada. Effectiveness of methadone maintenance therapy has been established, but recently newer treatment delivery models have emerged. Differences across these treatment models have not been examined. PURPOSE: This descriptive qualitative study used semi-structured interviews to assess client experiences in three methadone maintenance therapy treatment delivery models: (a) comprehensive programs, (b) low-threshold/high-tolerance programs, and (c) fee-for-service programs. METHODS: A total of 32 participants were recruited from methadone maintenance therapy clinics in an Atlantic Canadian city and grouped into three models of care (na = 9, nb = 11, nc = 12). Content analysis was performed on interview data to assess the frequency of relevant themes in the data. RESULTS: Participants from all groups stressed the importance of supportive staff and having access to some form of counselling. However, low-threshold/high-tolerance and fee-for-service clients voiced a need for more formal counselling and programming at their clinics. Methadone was reported as the most helpful aspect of the methadone maintenance therapy programs; however, participants also expressed negative views about the substance. CONCLUSIONS: These findings have important implications for the development and implementation of methadone maintenance therapy, specifically pertaining to further integration of addiction and mental health services.