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  1. Lua PL, Talib NS, Ismail Z
    J Pharm Pract, 2013 Dec;26(6):541-50.
    PMID: 23764566 DOI: 10.1177/0897190013489574
    This study intended to (1) describe the baseline patient satisfaction level and preferred coping strategies and (2) assess patient satisfaction and coping mechanisms pre- and postintervention. Patients on methadone maintenance treatment (MMT) in Terengganu, Malaysia, were randomized into either MMT or MMT plus auricular acupuncture (MMT + AA) groups. All received the standard MMT, while participants on MMT + AA underwent concurrent AA session thrice weekly for 2 months (each session = 30 minutes). Data analysis was carried out using SPSS 16.0, employing descriptive and nonparametric statistics. Participations were received from 97 eligible male patients (median age = 36.0 years; Malay = 97.9%). After screening for dropouts, only 69 patients were considered for subsequent analysis (MMT = 40; MMT + AA = 29). At preintervention, both groups did not differ significantly in the parameters investigated. During postintervention, no significant difference was detected for satisfaction level but coping-wise, substance use was significantly and frequently adopted by MMT + AA patients compared to MMT respondents (P < .05). On separate analysis, those who received MMT alone adopted active coping, venting, and self-blame significantly more frequently postintervention (P < .05). Nevertheless, no significant difference for coping styles of MMT + AA patients was exhibited over time (P >.05). The addition of AA therapy into the standard MMT treatment did not seem to influence patient satisfaction and their coping ways.
    Matched MeSH terms: Methadone/administration & dosage*
  2. Nik Jaafar NR, Mislan N, Abdul Aziz S, Baharudin A, Ibrahim N, Midin M, et al.
    J Sex Med, 2013 Aug;10(8):2069-76.
    PMID: 23445463 DOI: 10.1111/jsm.12105
    INTRODUCTION: While methadone effectively treats opiate dependence, the side effect of erectile dysfunction (ED) may interfere with treatment adherence and benefits.
    AIM:To determine the rate of ED and the associated factors which predict ED in male patients on methadone maintenance therapy (MMT) in a Malaysian population.
    MAIN OUTCOME MEASURES: The main outcome measures were the International Index of Erectile Function-15 (IIEF-15) and the Beck Depression Inventory (BDI).
    METHODS: A total of 108 participants diagnosed with heroin dependence were assessed. We used the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I) on subjects who received MMT, and they were assessed using the IIEF-15, the BDI, and measures of other clinical and sociodemographic variables.
    RESULTS: The rate of ED among men on MMT was 68.5% (mild ED, 36.1%; mild to moderate ED, 22.2%; severe ED, 3.7%). The mean age of the participants was 43.45 years. Older age (P = 0.002), concurrent illicit heroin use (P = 0.024), and having an older partner (P = 0.039) were significantly associated with ED. Following multivariate analysis, it was found that older age was the only significant predictor of ED, with an adjusted odds ratio of 1.07 (95% CI = 1.02-1.16). Methadone dose and duration of methadone treatment were not significantly associated with ED.
    CONCLUSION: ED was highly prevalent among male patients on MMT. This suggests that there is a need for routine assessment of sexual function in patients on methadone. Among the risk factors, age was the only factor that was significantly associated with ED. The current use of MMT in Malaysia in terms of dosage and duration did not pose a significant risk for ED.
    KEYWORDS: Erectile Dysfunction; Methadone Therapy; Opiate Dependence
    Study site: outpatient clinic for opiate substitution therapy, Hospital Kuala Lumpur (HKL), Malaysia
    Matched MeSH terms: Methadone/administration & dosage
  3. Aziz Z, Chong NJ
    J Subst Abuse Treat, 2015 Jun;53:47-51.
    PMID: 25616750 DOI: 10.1016/j.jsat.2014.12.008
    The aim of this study was to examine opioid-dependent patients' satisfaction with the methadone maintenance treatment (MMT) program in Malaysia and identify predictors of satisfaction. We used an interviewer-administered questionnaire developed and validated by Rankin Court, New South Wales, Australia. Of 502 patients approached in 11 MMT centers in Malaysia, 425 agreed to participate giving a response rate of 85%. In terms of overall satisfaction, a high percentage of respondents (85%) were satisfied with the MMT services. A logistic regression analysis showed that only "centres" and marital status were associated with overall satisfaction and that being single (OR 3.31; 95% CI 1.52 to 7.20) or married (OR 4.06; 95% CI 1.76 to 9.38) was associated with higher odds of overall satisfaction compared to being divorced or separated. An analysis of the responses pertaining to the most desired changes required at the center found dosing hours, waiting area and staff shortages to be common. The findings acquired from this survey will be useful to attain a clearer perspective on what aspects of the MMT service need to be reviewed for the improvement of service delivery.
    Matched MeSH terms: Methadone/administration & dosage*
  4. Yee A, Loh HS, Danaee M, Riahi S, Ng CG, Sulaiman AH
    J Sex Med, 2018 02;15(2):159-166.
    PMID: 29275046 DOI: 10.1016/j.jsxm.2017.12.004
    BACKGROUND: Methadone has been recognized as an effective maintenance treatment for opioid dependence. However, its use is associated with several complications, including sexual dysfunction in men.

    AIM: To assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT).

    METHODS: 76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale.

    OUTCOMES: Prevalence and associated factors of TT level lower than the reference range in men on MMT or BMT.

    RESULTS: More than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = -0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups.

    CLINICAL IMPLICATIONS: The sex hormonal assay should be used regularly to check men on MMT.

    STRENGTHS AND LIMITATIONS: This is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin.

    CONCLUSIONS: The findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting. Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159-166.

    Matched MeSH terms: Methadone/administration & dosage*
  5. Wickersham JA, Marcus R, Kamarulzaman A, Zahari MM, Altice FL
    Bull World Health Organ, 2013 Feb 01;91(2):124-9.
    PMID: 23554524 DOI: 10.2471/BLT.12.109132
    PROBLEM: In Malaysia, human immunodeficiency virus (HIV) infection is highly concentrated among people who inject opioids. For this reason, the country undertook a three-phase roll-out of a methadone maintenance treatment (MMT) programme. In Phase 3, described in this paper, MMT was implemented within prisons and retention in care was assessed.

    APPROACH: After developing standard operating procedures and agreement between its Prisons Department and Ministry of Health, Malaysia established pilot MMT programmes in two prisons in the states of Kelantan (2008) and Selangor (2009) - those with the highest proportions of HIV-infected prisoners. Community-based MMT programmes were also established in Malaysia to integrate treatment activities after prisoners' release.

    LOCAL SETTING: Having failed to reduce the incidence of HIV infection, in 2005 Malaysia embarked on a harm reduction strategy.

    RELEVANT CHANGES: STANDARD OPERATING PROCEDURES WERE MODIFIED TO: (i) escalate the dose of methadone more slowly; (ii) provide ongoing education and training for medical and correctional staff and inmates; (iii) increase the duration of methadone treatment before releasing prisoners; (iv) reinforce linkages with community MMT programmes after prisoners' release; (v) screen for and treat tuberculosis; (vi) escalate the dose of methadone during treatment for HIV infection and tuberculosis; and (vii) optimize the daily oral dose of methadone (> 80 mg) before releasing prisoners.

    LESSONS LEARNT: Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates.

    Matched MeSH terms: Methadone/administration & dosage
  6. Teoh Bing Fei J, Yee A, Habil MH, Danaee M
    J Subst Abuse Treat, 2016 10;69:50-6.
    PMID: 27568510 DOI: 10.1016/j.jsat.2016.07.006
    Methadone maintenance therapy has been found to be an effective harm reduction treatment for opioid use disorder. However evidence of its benefits over a longer duration of treatment is limited as most studies focus on its short term benefits. As methadone maintenance therapy reaches a decade since its implementation in Malaysia, this study sought to examine the effectiveness of methadone treatment, change in quality of life among patients since entry to methadone treatment, as well as factors predicting the magnitude of change in quality of life. This study found that methadone maintenance therapy was effective in reducing heroin use, injecting practices and crime, and in improving in social functioning and physical symptoms, but not in reducing sex-related HIV risk-taking behavior. Though patients had a significantly better quality of life at follow-up than at entry to methadone maintenance therapy, the improvement in quality of life was not significantly greater as the duration of treatment increased. Age above 50 years old, human immunodeficiency virus (HIV) positive status and physical symptoms predicted a poorer improvement in quality of life between baseline and follow-up. On the other hand, patients with hepatitis B showed a greater improvement in quality of life in the social relationships domain compared to patients without hepatitis B. In conclusion, methadone maintenance therapy is an effective treatment for opioid use disorder and improves quality of life but its benefits in further improving quality of life beyond a decade of treatment need further evaluation.
    Matched MeSH terms: Methadone/administration & dosage*
  7. Motlagh F, Ibrahim F, Rashid R, Shafiabady N, Seghatoleslam T, Habil H
    Psychopharmacology (Berl), 2018 Nov;235(11):3273-3288.
    PMID: 30310960 DOI: 10.1007/s00213-018-5035-0
    Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain electrical abnormalities among heroin addicts. This study aims to investigate the acute and short-term effects of methadone administration on the brain's electrophysiological properties before and after daily methadone intake over 10 weeks of treatment among heroin addicts. EEG spectral analysis and single-trial event-related potential (ERP) measurements were used to investigate possible alterations in the brain's electrical activities, as well as the cognitive attributes associated with MMN and P3. The results confirmed abnormal brain activities predominantly in the beta band and diminished information processing ability including lower amplitude and prolonged latency of cognitive responses among heroin addicts compared to healthy controls. In addition, the alteration of EEG activities in the frontal and central regions was found to be associated with the withdrawal symptoms of drug users. Certain brain regions were found to be influenced significantly by methadone intake; acute effects of methadone induction appeared to be associative to its dosage. The findings suggest that methadone administration affects cognitive performance and activates the cortical neuronal networks, resulting in cognitive responses enhancement which may be influential in reorganizing cognitive dysfunctions among heroin addicts. This study also supports the notion that the brain's oscillation powers and ERPs can be utilized as neurophysiological indices for assessing the addiction treatment traits.
    Matched MeSH terms: Methadone/administration & dosage*
  8. AlMeman AA, Ismail R, Perola M
    Drug Metab Lett, 2016;10(3):213-218.
    PMID: 27515451
    INTRODUCTION: Methadone is accepted as an alternative therapy in opioid use disorders worldwide. Methadone responsiveness, however, is affected by a range of CYP450 enzymes and OPRM1 polymorphisms.

    OBJECTIVE: This study sought to detect CYP2B6 and OPRM1 variants and their genotypes, as major contributors to inter-variability in methadone responsiveness and methadone dose requirements.

    METHODS: We carried out a prospective experimental one-phase pharmacogenetic study in four addiction clinics in Malaysia. Patients on stable methadone maintenance therapy were recruited. The prevalence of the CYP2B6 and OPRM1 polymorphisms was determined using a nested polymerase chain reaction (PCR), followed by genotyping. A two-step multiplex PCR method was developed to simultaneously detect the 26 SNPs in these two genes.

    RESULTS: 120 males were recruited for this study. The patients were between 21and 59 years old, although the majority of the patients were in their 30s. C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1 were found to be polymorphic, and the allelic frequencies of each were calculated. We further detected eight new haplotypes.

    CONCLUSION: C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1were found to be polymorphic. The new haplotypes may give a new insight on methadone clinics.

    Matched MeSH terms: Methadone/administration & dosage
  9. Ramli FF
    Bosn J Basic Med Sci, 2021 Apr 01;21(2):145-154.
    PMID: 32841585 DOI: 10.17305/bjbms.2020.4897
    Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. Pharmacogenomic biomarkers seem promising for personalized methadone maintenance treatment. The evidence supports the use of ABCB1 single-nucleotide polymorphism (SNP) 1236C>T with genotypes C/T or C/C (Jewish) and haplotypes AGCTT carrier, AGCGC heterozygote, or non-carrier (Caucasian), which have a predicted lower methadone dose requirement. In contrast, ABCB1 SNP 1236C>T with genotype T/T (Jewish); haplotypes AGCGC homozygote, AGCTT non-carrier (Caucasian), and ABCB1 3435C>T variant carrier; and haplotypes CGT, TTC, and TGT (Han Chinese) have a predicted higher methadone dose. For methadone plasma levels, ABCB1 diplotype non-CGC/TTT (Malay) predicted lower, and diplotype CGC/TTT (Malay), 3435C>T allelic carrier, haplotypes (CGT, TTC, TGT) (Han Chinese) predicted higher methadone levels. In terms of metabolism biomarkers, a lower methadone requirement was related to carriers of CYP2B6 genotypes *4(G/G) and *9(T/T) among Jewish patients, CYP2B6*9 genotype (T/T) and haplotypes (TA/TG); and CYP2C19 (*2/*2,*2/*3, and *3/*3; Han Chinese). Higher methadone dose was observed in CYP2C19*1 allelic carriers (Han Chinese) and CYP2D6 ultrarapid metabolizer (Caucasian). Lower methadone levels were reported in CYP2B6 SNPs, haplotypes TTT, and AGATAA (Han Chinese), CYP2C19 genotype *1/*1 (Han Chinese), allelic carrier *1xN (Caucasian), and CYP3A4 genotype *1/*1 (Caucasian). Carriers of CYP2B6 genotype *6/*6 (Caucasian), CYP2B6 haplotypes ATGCAG and ATGCTG (Han Chinese), and CYP3A4 genotype *1/*1B (Caucasian) had predicted higher methadone plasma levels. Specific pharmacokinetics biomarkers have potential uses for personalized methadone treatment in specific populations.
    Matched MeSH terms: Methadone/administration & dosage
  10. Ramli FF, Syed Hashim SA, Mohd Effendy N
    Int J Med Sci, 2021;18(2):575-581.
    PMID: 33390827 DOI: 10.7150/ijms.52201
    Background: Long-term opioid therapy is a risk factor for low bone mineral density (BMD). However, other factors may also contribute to low BMD. Several studies have examined the variables that might contribute to low BMD in patients receiving opioid replacement therapy (OST). However, to our knowledge, there was no systemic review conducted to address this particular issue. Thus, we reviewed the articles on the factors associated with low BMD in the population of opioid use disorder receiving substitution therapy. Methods: The articles that examined correlates or risk factors of low BMD in OST population were retrieved from OVID, SCOPUS, and PUBMED from inception until July 2020 by two independent investigators. Results: A total of 429 articles from three databases were retrieved initially. After screening based on eligibility criteria, five articles were included in the final analysis. The risk factors or correlates found to be significantly associated with low BMD in the OST population include male gender, low body mass index, low testosterone level, methadone or heroin use, and longer duration of heavy alcohol use. The review limitations include small sample sizes and inconsistent definition of variables. Conclusion: OST patients should be screened for BMD and its associated factors. Guidelines and training of practitioners involving in the OST service should be provided to increase the detection of low BMD in the OST population.
    Matched MeSH terms: Methadone/administration & dosage
  11. Yee A, Loh HS, Ong TA, Ng CG, Sulaiman AH
    Am J Mens Health, 2018 Sep;12(5):1705-1718.
    PMID: 29973132 DOI: 10.1177/1557988318784152
    Methadone is largely recognized as an effective treatment for opiate-dependent patients; however, it causes reduced brain dopaminergic action resulting in significant sexual dysfunction. Bupropion is a dopamine reuptake inhibitor which can potentially improve erectile function among male patients on methadone (MMT). This is a phase II, randomized, double-blind, parallel-group, placebo-controlled trial, involving 80 MMT male patients (73.4%) with mean age of 42.83 years ±9.68. These MMT male patients were randomly assigned into two groups to receive bupropion and placebo, respectively. The primary efficacy outcome measure was the difference between the two groups in end-point mean improvement scores using the measurement of Clinical Global Impression Scale adapted for Sexual Function (CGI-SF) at baseline (week 0) and at weeks 2, 4, and 6. Malay version of the sexual desire inventory-2 (SDI-2-BM) and Malay version of International Index of Erectile Function 15 (Mal-IIEF-15) domain scores were evaluated as secondary parameters. Improvement of the end-point mean from baseline were seen across the scores of SDI-2-BM (mean difference = 11.77 ± 2.90, 95% confidence interval (CI) [3.89, 19.54], p < .001) and Mal-IIEF-15 (mean difference = 8.37 ± 2.71, 95% CI [15.75, 0.99], p = .02), and the total plasma testosterone level (mean difference = 4.03, 95% CI [0.90, 7.15], p = .01). A categorical improvement of "much/very much improved" (CGI-SF score = 2) was reported by 58.3% ( n = 21/36) of bupropion SR-assigned versus 27.7% ( n = 10/36) placebo-assigned patient. Bupropion was well tolerated with no serious adverse events reported other than insomnia (17.7%). Six weeks of bupropion SR treatment reported significant improvement in key aspects of sexual function among male opiate-dependent patients on methadone maintenance treatment with emergent sexual dysfunction.
    Matched MeSH terms: Methadone/administration & dosage
  12. Wickersham JA, Zahari MM, Azar MM, Kamarulzaman A, Altice FL
    Drug Alcohol Depend, 2013 Sep 01;132(1-2):378-82.
    PMID: 23414931 DOI: 10.1016/j.drugalcdep.2013.01.005
    OBJECTIVE: To evaluate the impact of methadone dose on post-release retention in treatment among HIV-infected prisoners initiating methadone maintenance treatment (MMT) within prison.

    METHODS: Thirty HIV-infected prisoners meeting DSM-IV pre-incarceration criteria for opioid dependence were enrolled in a prison-based, pre-release MMT program in Klang Valley, Malaysia; 3 died before release from prison leaving 27 evaluable participants. Beginning 4 months before release, standardized methadone initiation and dose escalation procedures began with 5mg daily for the first week and 5mg/daily increases weekly until 80 mg/day or craving was satisfied. Participants were followed for 12 months post-release at a MMT clinic within 25 kilometers of the prison. Kaplan-Meier survival analysis was used to evaluate the impact of methadone dose on post-release retention in treatment.

    FINDINGS: Methadone dose ≥80 mg/day at the time of release was significantly associated with retention in treatment. After 12 months of release, only 21.4% of participants on <80 mg were retained at 12 months compared to 61.5% of those on ≥80 mg (Log Rank χ(2)=(1,26) 7.6, p<0.01).

    CONCLUSIONS: Higher doses of MMT at time of release are associated with greater retention on MMT after release to the community. Important attention should be given to monitoring and optimizing MMT doses to address cravings and side effects prior to community re-entry from prisons.

    Matched MeSH terms: Methadone/administration & dosage*
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