METHODS: The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose.
RESULTS: Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016).
CONCLUSIONS: This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively.
METHODS: The cold pressor pain responses of 148 opioid dependent patients receiving MMT were evaluated using the cold pressor test (CPT). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping.
RESULTS: Of the 148 subjects, 77 (52.0%) were carriers of CYP2B6*6 allele. CYP2B6*6 allele carriers had shorter cold pain threshold and pain tolerance times than non-carriers of CYP2B6*6 allele (21.05s vs 33.69s, p=0.036 and 27.15s vs 44.51s, p=0.020, respectively). Pain intensity scores of the CYP2B6*6 allele carriers was 67.55, whereas that of the CYP2B6*6 allele non-carriers was 64.86 (p=0.352).
CONCLUSION: Our study indicates that the CYP2B6*6 allele is associated with a lower pain threshold and lower pain tolerance among males with opioid dependence on MMT. The CYP2B6*6 allele may provide a mechanistic explanation for clinical observations of heightened pain sensitivity among opioid dependent patients receiving MMT.
Materials and Methods: Patients with opioid dependence (n = 148) were recruited from MMT clinics. Pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality were assessed using cold pressor test (CPT), Subjective Opiate Withdrawal Scale (SOWS-M), and Pittsburgh Sleep Quality Index (PSQI)-Malay, respectively. Deoxyribonucleic acid (DNA) was extracted from whole blood, and then was used for genotyping of Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms.
Results: Among 148 patients, 8.1% (n = 12), 60.8% (n = 90), 27.7% (n = 41), and 29.1% (n = 43) had at least one risk allele for Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms, respectively. There were no significant differences in pain responses (pain threshold, tolerance, and intensity), SOWS, and PSQI scores between DRD2 polymorphisms.
Conclusion: The common DRD2 polymorphisms are not associated with pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality in patients with opioid dependence on MMT. However, this may be unique for Malays. Additional research should focus on investigating these findings in larger samples and different ethnicity.
MATERIALS AND METHODS: Participants comprised Malay male opioid-naive subjects (n = 159) and opioid-dependent patients (n = 160) from MMT clinics in Kelantan, Malaysia, between March and October 2013. Sleep quality was evaluated using the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI).
RESULTS: The opioid-dependent patients exhibited higher global PSQI scores [adjusted mean (95% CI) = 5.46 (5.02, 5.90)] than the opioid-naive group [4.71 (4.26, 5.15)] [F (1, 313) = 4.77, P = 0.030].
CONCLUSION: This study confirmed the poorer sleep quality among opioid-dependent patients on MMT, as manifested by their higher global PSQI scores. The sleep complaints in this patient population are a factor to consider and, when necessary, sleep evaluation and treatment should be undertaken to improve MMT patients' quality of sleep and overall treatment outcome.
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.
METHODS: Clinical records of active opioid dependents who underwent MMT between 1 January 2007 and 31 March 2021 in Hospital Tuanku Fauziah, Perlis, Malaysia were retrospectively reviewed. Data collected included baseline demographics, history of illicit drug use, temporal trend in methadone dosage modulation, and co-use of illicit drugs during the MMT.
RESULTS: A total of 87 patients (mean age, 43.9 ± 8.33 years) were included. Their mean duration of involvement in MMT was 7.8 ± 3.69 years. The most commonly used drug was heroin (88.5%), followed by kratom (51.7%). Between 2019 and 2021, 61 (70.1%) patients had ceased abusing opioid, but 51 (58.6%) patients continued using any of the illicit drugs. Methamphetamine and amphetamine co-use was most common (n = 12, 37.5%). Hepatitis C status was not associated with the current methadone dose (U = 539.5, p = 0.186) or the highest dose required (t = -0.291, df = 74, p = 0.772). No predictor for illicit drug abstinence during MMT was identified. Methadone dose positively correlated with frequency of defaulting treatments (r = 0.22, p = 0.042).
CONCLUSION: Among our patients, MMT for opioid dependents cannot sufficiently curb illicit drug use, and there is a shift toward stimulants abuse.
METHODS: We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098).
FINDINGS: Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse 31 days [IQR 26-32] vs 352 days [256-unestimable], log rank test, p<0·0001). VTC participants had an 84% (95% CI 75-90) decreased risk of opioid relapse after adjustment for control variables and inverse propensity of treatment weights. Time-varying effect modelling revealed the largest hazard ratio reduction, at 91% (95% CI 83-96), occurs during the first 50 days in the community.
INTERPRETATION: Opioid-dependent individuals in CDDCs are significantly more likely to relapse to opioid use after release, and sooner, than those treated with evidence-based treatments such as methadone, suggesting that CDDCs have no role in the treatment of opioid-use disorders.
FUNDING: The World Bank Group, Doris Duke Charitable Foundation, National Institute on Drug Abuse, Australian National Health & Medical Research Council, National Institute of Mental Health, and the University of Malaya-Malaysian Ministry of Higher Education High Impact Research Grant.