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  1. Khalid K, Anuar A, Ang WC, Jamaluddin R
    Curr Drug Saf, 2023;18(2):167-174.
    PMID: 35570535 DOI: 10.2174/1574886317666220514154931
    BACKGROUND: Per oral methadone maintenance therapy [MMT] was introduced as part of harm reduction strategy to manage rising numbers of HIV infections caused by intravenous use of illicit drugs.

    METHOD: We aim to review published articles related to the side effects of long-term methadone therapy, focusing on hematological derangements in human studies published between 1 January 2000 till 31 January 2021.

    RESULTS: Our search databases include Web of Science, Scopus, and Medline. Our search yielded 971 articles, of which 55 articles were related to the effects of MMT on various organ systems: cardiovascular [n=12], respiratory [n=1], endocrine [n=10], central nervous system [n=12], neurobehavioral [n=10], gastrointestinal [n=1], and bone [n=1]. There were eight articles specifically related to the hematological side effects of chronic methadone therapy that include [i] immune system hyperactivation, [ii] reduced circulating lymphocytes, and [iii] increased blood viscosity.

    CONCLUSION: In view of all foreseeable health risks seen with prolonged methadone therapy, pharmacological modulation is warranted to find a better substitute for managing patients with opioid dependence.

    Matched MeSH terms: Methadone/adverse effects
  2. Yee A, Loh HS, Hisham Hashim HM, Ng CG
    Int J Impot Res, 2014 Sep-Oct;26(5):161-6.
    PMID: 24990199 DOI: 10.1038/ijir.2014.18
    Methadone maintenance treatment is proven to be effective treatment for opioid dependence. Of the many adverse events reported, sexual dysfunction is one of the most common side effects. However, there may be other clinical factors that are associated with sexual dysfunction among methadone users. We conducted a meta-analysis to examine the clinical factors associated with sexual dysfunction among male patients on methadone and buprenorphine treatments, of which eligible studies were selected using prior defined criteria. A total of 2619 participants from 16 eligible studies, published from inception till December 2012, were identified from the PubMed, OVID and EMBASE databases. The included studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval (CI), 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (odds ratio=4.01, 95% CI, 1.52-10.55, P=0.0049). Our study shows that eight clinical factors are associated with sexual dysfunction among men receiving opioid substitution treatment, namely age, hormone assays, duration of treatment, methadone dose, medical status, psychiatric illness, other current substance use and familial status, and methadone versus buprenorphine treatment. Despite the methodological limitations, the findings of this meta-analysis study may offer better insights to clinicians in dealing with both sexual dysfunction and its related problems.
    Matched MeSH terms: Methadone/adverse effects*
  3. George P, Vicknasingam B, Thurairajasingam S, Ramasamy P, Mohd Yusof H, Yasin MABM, et al.
    Drug Alcohol Rev, 2018 Jan;37(1):147-151.
    PMID: 27859761 DOI: 10.1111/dar.12456
    INTRODUCTION AND AIMS: Opioid dependence remains the main type of illicit substance used in Malaysia, which has an estimated 187 771 opiate users. There are currently 333 active methadone maintenance treatment centres nationwide. Although methadone has proven to be an effective maintenance therapy, it has clinical concerns which can have an impact on its effectiveness and safety.

    DESIGN, METHODS AND RESULTS: A case series of seven patients from Malaysian private and public hospital settings who had an adverse reaction with methadone is discussed.

    DISCUSSION AND CONCLUSION: Despite methadone being an effective therapy for opioid dependence, there is a need for other alternative effective therapies, such as naltrexone, buprenorphine and the co-formulation of buprenorphine-naloxone, to be made available to physicians in both public and private sectors. There is need for individual treatment consideration to avoid adverse effects, drug-drug interactions, overdosing and in the presence of co-morbidities. An emphasis on safe storage of takeaway methadone is also needed. [George P, Vicknasingam B, Thurairajasingam S, Ramasamy P, Mohd Yusof H, Yasin MABM, Shah ZUBS. Methadone complications amongst opioid-dependent patients in Malaysia: A case series. Drug Alcohol Rev 2018;37:147-151].

    Matched MeSH terms: Methadone/adverse effects*
  4. Yee A, Danaee M, Loh HS, Sulaiman AH, Ng CG
    PLoS One, 2016;11(1):e0147852.
    PMID: 26820154 DOI: 10.1371/journal.pone.0147852
    INTRODUCTION: Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients.

    METHODS: Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders.

    RESULTS: The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables.

    CONCLUSIONS: Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when treating heroin dependents who have concerns about sexual function.

    Matched MeSH terms: Methadone/adverse effects*
  5. Yee A, Loh HS, Hisham Hashim HM, Ng CG
    J Sex Med, 2014 Jan;11(1):22-32.
    PMID: 24344738 DOI: 10.1111/jsm.12352
    INTRODUCTION: For many years, methadone has been recognized as an effective maintenance treatment for opioid dependence. However, of the many adverse events reported, sexual dysfunction is one of the most common side effects.

    AIM: We conducted a meta-analysis to evaluate the prevalence of sexual dysfunction among male patients on methadone and buprenorphine treatments.

    METHODS: Relevant studies published from inception until December 2012 were identified by searching PubMed, OVID, and Embase. Studies were selected using prior defined criteria. Heterogeneity, publication bias, and odds ratio were assessed thoroughly.

    MAIN OUTCOME MEASURES: To examine the prevalence and odds ratio of sexual dysfunctions among the methadone and buprenorphine groups.

    RESULTS: A total of 1,570 participants from 16 eligible studies were identified in this meta-analysis. The studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval [CI], 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (OR = 4.01, 95% CI, 1.52-10.55, P = 0.0049).

    CONCLUSIONS: Evidence showed that the prevalence of sexual dysfunction was higher among the users of methadone compared with buprenorphine. Patients with sexual difficulty while on methadone treatment were advised to switch to buprenorphine.

    Matched MeSH terms: Methadone/adverse effects*
  6. Yee A, Loh HS, Ng CG, Sulaiman AH
    Am J Mens Health, 2018 07;12(4):1016-1022.
    PMID: 29493379 DOI: 10.1177/1557988318759197
    Low sexual desire (SD) is not life threatening, but its negative impact on the quality of life and intimacy of a relationship among the patients on methadone maintenance therapy (MMT) is significant. This cross-sectional study involved 183 men on MMT who were interviewed and who completed the Malay version of the SDI-2 (SDI-2-BM), the Malay version of the self-rated Montgomery-Asberg Depression Rating Scale (MADRS-BM) and World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) questionnaires. Findings showed 32.8% ( n = 60) participants had low SD. Those who were older, had sexual partners, and were smokers achieved lower scores in both dyadic SD (≤24) and solitary SD (≤6), and suffered lower quality of life in their social relationship. MMT is very cost-effective in rehabilitating opioid dependence; however, as clinicians, we need to address and manage the issues of low SD and depression among patients on MMT, especially the older men.
    Matched MeSH terms: Methadone/adverse effects
  7. 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/adverse effects*
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