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Journal articles on the topic 'Methadone maintenance Physiological effect'

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Author: Grafiati

Published: 10 December 2022

Last updated: 29 January 2023

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1

Rezai, Marzieh, Mohammad Reza Hajizadeh, Mehdi Mahmoodi, Seyedeh Atekeh Torabizadeh, and Mojgan Noroozi Karimabad. "Effect of Methadone Maintenance on Expression of BDNF and CREB Genes in Brain VTA of Male Morphine Treated Rats." Central Nervous System Agents in Medicinal Chemistry 21, no. 3 (October 2021): 181–86. http://dx.doi.org/10.2174/1871524922666211223153555.

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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.

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Murnion, Bridin Patricia, Consuelo Rivas, Apo Demirkol, Vicky Hayes, Nicholas Lintzeris, and Suzanne Nielsen. "Acute Experimental Pain Responses in Methadone- and Buprenorphine/Naloxone-Maintained Patients Administered Additional Opioid or Gabapentin: A Double-Blind Crossover Pilot Study." Pain Medicine 21, no. 6 (August 24, 2019): 1188–98. http://dx.doi.org/10.1093/pm/pnz178.

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Abstract Objective The study objective was to identify the analgesic efficacy of three different pharmacological strategies in patients receiving methadone or buprenorphine as opioid agonist treatment (OAT). The three pharmacological approaches, a) increasing maintenance methadone/buprenorphine dose by 30%, b) adding oxycodone, or c) adding a single dose of gabapentin, were compared with a control condition of the participant’s usual OAT dose. Design A randomized, controlled, double-blinded, double-dummy, within-subject crossover study. Subjects Nine participants on stable doses of methadone and eight participants on stable doses of buprenorphine were recruited. Setting An outpatient opioid treatment clinic in inner city Sydney, Australia. Methods The cold pressor tolerance test was used to examine experimental pain threshold and tolerance. Ratings of subjective drug effects and safety measures (physiological and cognitive) were assessed. Results There was no difference in the primary outcome measures of pain thresholds or tolerance between the conditions examined. Interindividual variability was evident. Differences in some subjective measures were identified, including lower pain recall, lower “bad effects,” and higher global satisfaction in the additional methadone condition. In the buprenorphine arm, increased drug liking and “bad effects” were detected with oxycodone administration, while increased subjective intoxication was identified with gabapentin. Conclusions There was no evidence of an objective improvement in analgesia with any condition compared with control. Further research is required to optimize pain management strategies in this population.

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Alemán-Laporte, Jilma, Luciana A. Bandini, Mariana SA Garcia-Gomes, Dennis A. Zanatto, Denise T. Fantoni, Marco A. Amador Pereira, Pedro E. Navas-Suárez, et al. "Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization." Laboratory Animals 54, no. 2 (May 30, 2019): 171–82. http://dx.doi.org/10.1177/0023677219850211.

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In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory rats of both sexes. Ultrasonic vocalization (USV) was used as an indicator of pain during the recovery period. The objective was to evaluate the physiological parameters and the analgesic effect of each protocol to determine which protocol was the safest and fulfil the requirements of a balanced anaesthesia. The better protocols were the XKA protocol for both sexes and the XKMe protocol for females because the combinations achieve surgical plane of anaesthesia in rats. However, pain assessment during the formalin test revealed that rats anaesthetized with XKA produced more numbers of USV, suggesting that it is not a good protocol for the control of immediate postoperative pain. All protocols produced depression in body temperature and respiratory and heart rates, and had important effects, such as micturition and maintenance of open eyes. Only rats anaesthetized with XKA protocol did not present piloerection. These results demonstrated that good monitoring and care during anaesthesia must be included to prevent complications that compromise the life of the animal and to ensure a good recovery. The inclusion of analgesia in anaesthesia protocols must be used routinely, ensuring minimal presence of pain and thus more reliable results in the experimental procedures.

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Daglish, Mark R. C., Tim M. Williams, Sue J. Wilson, Lindsay G. Taylor, Chin B. Eap, Marc Augsburger, Christian Giroud, et al. "Brain dopamine response in human opioid addiction." British Journal of Psychiatry 193, no. 1 (July 2008): 65–72. http://dx.doi.org/10.1192/bjp.bp.107.041228.

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BackgroundDrugs of dependence cause dopamine release in the rat striatum. Human neuroimaging studies have shown an increase in dopamine in the equivalent region in response to stimulants and other drugsAimsWe tested whether opioids provoke dopamine release and its relationship to the subjective experienceMethodIn two combined studies 14 heroin addicts on methadone maintenance treatment underwent two positron emission tomography brain scans of the dopamine system using [11C]-raclopride following an injection of placebo and either 50 mg intravenous diamorphine or 10 mg subcutaneous hydromorphone in a double-blind, random order designResultsBoth opioids produced marked subjective and physiological effects, but no measurable change in [11C]-raclopride bindingConclusionsThe absence of a dopamine response to opioid agonists contrasts with that found with stimulant drugs and suggests dopamine may not play the same role in addiction to opioids. This questions the role of dopamine in the subjective experience of heroin in opioid addicts

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5

P. Hamilton, Edward V. Nunes, Malvi, Steven. "The Effect of Sertraline on Methadone Plasma Levels in Methadone-Maintenance Patients." American Journal on Addictions 9, no. 1 (January 2000): 63–69. http://dx.doi.org/10.1080/10550490050172236.

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6

Umbricht, Annie, Jennifer R. Schroeder, Denis G. Antoine, David A. Tompkins, Crystal Barnhouser, Eric C. Strain, and George Bigelow. "Topiramate effect on weight gain during methadone maintenance." Drug and Alcohol Dependence 156 (November 2015): e227. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.611.

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7

Maddux, James F., and David P. Desmond. "Outcomes of Methadone Maintenance 1 Year after Admission." Journal of Drug Issues 27, no. 2 (April 1997): 225–38. http://dx.doi.org/10.1177/002204269702700204.

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The authors followed a cohort of 610 opioid users for 1 year after admission to methadone maintenance. At the end of the year, 52% were on methadone and 48% were off methadone. Among subjects on methadone, days of intravenous drug use, crime, and needle-sharing decreased markedly from the month preceding admission to the month preceding the first anniversary of admission. Among subjects off methadone, days of these activities also decreased, but the decreases appeared in large part to be an effect of increased days of incarceration. Among those on methadone, days of productive activity increased markedly. Subjects with more years of intravenous drug use were more likely to be on methadone at the end of the year, and subjects under compulsory supervision were less likely to be on methadone. The findings confirm previous reports of decreased illicit opioid use, decreased crime, and decreased needle risk for infection with the human immunodeficiency virus among opioid users who remain on methadone.

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Mitchell, Timothy B., Kyle R. Dyer, David Newcombe, Amy Salter, Andrew A. Somogyi, Felix Bochner, and Jason M. White. "Subjective and physiological responses among racemic-methadone maintenance patients in relation to relative (S)- vs. (R)-methadone exposure." British Journal of Clinical Pharmacology 58, no. 6 (December 2004): 609–17. http://dx.doi.org/10.1111/j.1365-2125.2004.02221.x.

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9

Stitzer, Maxine L., Warren K. Bickel, George E. Bigelow, and Ira A. Liebson. "Effect of methadone dose contingencies on urinalysis test results of polydrug-abusing methadone-maintenance patients." Drug and Alcohol Dependence 18, no. 4 (December 1986): 341–48. http://dx.doi.org/10.1016/0376-8716(86)90097-9.

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10

Zamir, S. M., H. Javdani, A. Massoudifar, M. Naghdipour, and A. Mehrnami. "The effect of aripiprazole on nicotine dependency in patients under methadone maintenance therapy." European Psychiatry 41, S1 (April 2017): S398. http://dx.doi.org/10.1016/j.eurpsy.2017.02.461.

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IntroductionThe prevalence of smoking in patients under methadone maintenance therapy is high (85–98%). Most of these patients tend to quit smoking, but only a few of them receive treatment or referred to quit smoking. Recent study on aripiprazole, has been shown to reduce smoking.AimsThe aim of this study was to evaluate aripiprazole on smoking in patients under methadone maintenance therapy.Material and methodThis study was a double-blind intervention study. Patients under Methadone maintenance therapy in 22 Bahman Hospital randomly divided into two intervention and control group. First with the FTQ questionnaire, nicotine dependency assessed in all patients. Then, 6-week aripiprazole administered to intervention group. Data were analyzed by SPSS version 21.ResultsThe age range of patients was 67–25 years. Two groups were matched in demographic characteristics. Finally, mean number of FTQ questionnaire in case group before intervention was 8.9 ± 1.4 and after intervention was 8.4 ± 1.6. This difference was statistically significant (P = 0.0007).ConclusionThe study results show the aripiprazole effect in reducing the desire to smoke in patients under methadone maintenance therapy. The overall level of dependency on nicotine on the basis of test FTQ has decreased. By choosing aripiprazole as adjunctive therapy to quit smoking, by reducing the tendency of patients to smoking, can decrease cardiovascular complications and other problems caused by smoking and we can reduce the mortality rate of these patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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11

BELL, JAMES, JOHN R. M. CAPLEHORN, and DONALD R. McNEIL. "The effect of intake procedures on performance in methadone maintenance." Addiction 89, no. 4 (April 1994): 463–71. http://dx.doi.org/10.1111/j.1360-0443.1994.tb00927.x.

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Kamal, Nik Nur Syazana Bt Nik Mohamed, Theam Soon Lim, Gee Jun Tye, Rusli Ismail, and Yee Siew Choong. "The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study." Journal of Chemistry 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/249642.

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Current methadone maintenance therapy (MMT) is yet to ensure 100% successful treatment as the optimum dosage has yet to be determined. Overdose leads to death while lower dose causes the opioid withdrawal effect. Single-nucleotide polymorphisms (SNP) in cytochrome P450s (CYPs), the methadone metabolizers, have been showen to be the main factor for the interindividual variability of methadone clinical effects. In this study, we investigated the effect of SNPs in three major methadone metabolizers (CYP2B6, CYP2D6, and CYP3A4) on methadone binding affinity. Results showed thatCYP2B6*11,CYP2B6*12,CYP2B6*18, andCYP3A4*12have significantly higher binding affinity toR-methadone compared to wild type.S-methadone has higher binding affinity inCYP3A4*3,CYP3A4*11, andCYP3A4*12compared to wild type.R-methadone was shown to be the active form of methadone; thus individuals with CYP alleles that binds better toR-methadone will have higher methadone metabolism rate. Therefore, a higher dosage of methadone is necessary to obtain the opiate effect compared to a normal individual and vice versa. These results provide an initial prediction on methadone metabolism rate for individuals with mutant type CYP which enables prescription of optimum methadone dosage for individuals with CYP alleles.

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Pani, Pier Paolo, Icro Maremmani, Matteo Pacini, Francesco Lamanna, Angelo G. I. Maremmani, and Liliana dell’Osso. "Effect of Psychiatric Severity on the Outcome of Methadone Maintenance Treatment." European Addiction Research 17, no. 2 (2011): 80–89. http://dx.doi.org/10.1159/000321465.

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14

Fareed, Ayman, Sreedevi Vayalapalli, Steven Stout, Jennifer Casarella, Karen Drexler, and Stephen P. Bailey. "Effect of Methadone Maintenance Treatment on Heroin Craving, a Literature Review." Journal of Addictive Diseases 30, no. 1 (December 30, 2010): 27–38. http://dx.doi.org/10.1080/10550887.2010.531672.

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15

Parpouchi, Milad, Akm Moniruzzaman, Stefanie N. Rezansoff, Angela Russolillo, and Julian M. Somers. "The effect of Housing First on adherence to methadone maintenance treatment." International Journal of Drug Policy 56 (June 2018): 73–80. http://dx.doi.org/10.1016/j.drugpo.2018.03.012.

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16

Rambe, Robiatun, Urip Harahap, and Citra Julita Tarigan. "INFLUENCE OF DOSAGE ON RETENTION IN PATIENTS METHADONE MAINTENANCE THERAPY PROGRAM FOR MAINTENANCE PHASE OF H. ADAM MALIK MEDAN CENTRAL GENERAL HOSPITAL." Asian Journal of Pharmaceutical and Clinical Research 11, no. 8 (August 7, 2018): 244. http://dx.doi.org/10.22159/ajpcr.2018.v11i8.24743.

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Objective: This study aims to see the effect of methadone dose on patient retention in following the program.Materials and Methods: This study is a clinical study with cross-sectional study design. Data obtained from the patient’s medical record and patient’s primary data. The study was conducted at Methadone Clinic of H.Adam Malik Hospital Medan. Results: The number of research samples is injecting drug users who follow PTRM as many as 39 people. From a study of 39 patients, the percentage of male patients (100%) was obtained; age between 25 and 35 years (64.1%); junior high school education equal to 84.6%; already married 46.2%; already working 69.2%; and the distance of the average residence with the clinic is 16.93 km. The results showed that the smallest maintenance dose of maintenance phase was 2 mg; the largest maintenance dose in the maintenance phase was 165 mg; the mean maintenance stage dose of 62.35 mg with a retention value >2 years or more (>730 days) was 79.5%.Conclusion: There was a significant effect on retention which is the biggest maintenance dose with p=0.04 value and take home dose with p=0.027. Percentage of drug use and other substances that is benzodiazepines (BZO) (64,1%); amphetamines (AMP) (38.5%); methamphetamine (MET) (20.5%); and THC (20.5%). There was no significant effect between the use of other substance to retention with p value of BZO (0.389); p AMP (0.360); p MET (0.195); and p THC (0.470). It can be concluded that the greater the dose of methadone has an effect on its retention.

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Bruce, R. Douglas, P. Winkle, J. M. Custodio, X. Wei, M. S. Rhee, B. P. Kearney, S. Ramanathan, and Gerald H. Friedland. "Investigation of the Interactions between Methadone and Elvitegravir-Cobicistat in Subjects Receiving Chronic Methadone Maintenance." Antimicrobial Agents and Chemotherapy 57, no. 12 (September 30, 2013): 6154–57. http://dx.doi.org/10.1128/aac.01229-13.

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ABSTRACTInteractions between HIV and opioid dependence therapies are known to occur. We sought to determine if such interactions occurred between methadone and elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD) boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic parameters. Safety and pharmacodynamics were monitored throughout the study. Compared to baseline values, theR-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to baseline values, theS-methadone mean AUCtau(7,040 versus 7,540 h · ng/ml) and meanCmax(446 versus 452 ng/ml) did not significantly increase in the presence of EVG/COBI. The AUCtau,Cmax, andCtauof elvitegravir and cobicistat did not significantly differ from those of historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. The addition of EVG/COBI to stabilized patients receiving methadone did not affect methadone pharmacokinetics and pharmacodynamics. These two agents can be safely coadministered.

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Trajanovska, Aneta, Viktorija Vujovic, Liljana Ignjatova, Danijela JanicevicIvanovska, and Aleksandar Cibisev. "Sexual Dysfunction as a Side Effect of Hyperprolactinemia in Methadone Maintenance Therapy." Medical Archives 67, no. 1 (2013): 48. http://dx.doi.org/10.5455/medarh.2013.67.48-50.

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Srivastava, Anita, Meldon Kahan, and Sue Ross. "The effect of methadone maintenance treatment on alcohol consumption: A systematic review." Journal of Substance Abuse Treatment 34, no. 2 (March 2008): 215–23. http://dx.doi.org/10.1016/j.jsat.2007.04.001.

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20

Moyer, Ruth A., and Greg Ridgeway. "The effect of outpatient methadone maintenance treatment facilities on place-based crime." Journal of Experimental Criminology 16, no. 2 (November 24, 2018): 227–45. http://dx.doi.org/10.1007/s11292-018-9347-1.

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21

Arora, Anshu, and Karen Williams. "Problem based review: The patient taking methadone." Acute Medicine Journal 12, no. 1 (January 1, 2013): 51–54. http://dx.doi.org/10.52964/amja.0285.

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Methadone Maintenance Treatment (MMT) is an effective therapy for opioid-dependence; its use is based on a harm reduction philosophy and represents one of a range of treatment approaches for opioid-dependent individuals. The medical literature supports MMT as a well established and cost-effective treatment for opioid-dependence that allows a return-to-normal physiological, psychological and societal functioning. The effectiveness of MMT is enhanced by psycho-social interventions such as contingency management and addressing other co-existing health and social needs. MMT saves lives and reduces violent and non-violent crime, drug use and the transmission of HIV, hepatitis C and other communicable diseases. For some people, MMT may continue for life, while others may eventually be able to discontinue and remain abstinent. Methadone interacts with numerous drugs and prolongs the corrected QT interval (QTc) with risk of sudden cardiac death. It has a prolonged half-life and premature discharge of patients after methadone overdose may be fatal. Each patient must be assessed, treated and monitored on an individual basis. Successful outcomes through MMT require knowledge, experience, vigilance, and diligence on the part of the physician, the patient and all of those involved in treatment.

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Vatter, Tatjana, Lukas Klumpp, Katrin Ganser, Nicolai Stransky, Daniel Zips, Franziska Eckert, and Stephan M. Huber. "Against Repurposing Methadone for Glioblastoma Therapy." Biomolecules 10, no. 6 (June 17, 2020): 917. http://dx.doi.org/10.3390/biom10060917.

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Methadone, which is used as maintenance medication for outpatient treatment of opioid dependence or as an analgesic drug, has been suggested by preclinical in vitro and mouse studies to induce cell death and sensitivity to chemo- or radiotherapy in leukemia, glioblastoma, and carcinoma cells. These data together with episodical public reports on long-term surviving cancer patients who use methadone led to a hype of methadone as an anti-cancer drug in social and public media. However, clinical evidence for a tumoricidal effect of methadone is missing and prospective clinical trials, except in colorectal cancer, are not envisaged because of the limited preclinical data available. The present article reviews the pharmacokinetics, potential molecular targets, as well as the evidence for a tumoricidal effect of methadone in view of the therapeutically achievable doses in the brain. Moreover, it provides original in vitro data showing that methadone at clinically relevant concentrations fails to impair clonogenicity or radioresistance of glioblastoma cells.

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Jaremko, Kellie M., Robert C. Sterling, and Elisabeth J. Van Bockstaele. "Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance." Journal of Substance Abuse Treatment 48, no. 1 (January 2015): 117–27. http://dx.doi.org/10.1016/j.jsat.2014.08.006.

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WOLK, JAEL, ALEX WODAK, JAMES J. GUINAN, PETRA MACASKILL, and JUDY M. SIMPSON. "The effect of a needle and syringe exchange on a methadone maintenance unit." Addiction 85, no. 11 (November 1990): 1445–50. http://dx.doi.org/10.1111/j.1360-0443.1990.tb01627.x.

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McMillan, Garnett P., Sandra Lapham, and Michael Lackey. "The effect of a jail methadone maintenance therapy (MMT) program on inmate recidivism." Addiction 103, no. 12 (December 2008): 2017–23. http://dx.doi.org/10.1111/j.1360-0443.2008.02361.x.

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Powers, Keiko I., and M. Douglas Anglin. "A Differential Assessment of the Cumulative Versus Stabilizing Effect of Methadone Maintenance Treatment." Evaluation Review 22, no. 2 (April 1998): 175–206. http://dx.doi.org/10.1177/0193841x9802200202.

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Corsi, Karen F., Wayne K. Lehman, and Robert E. Booth. "The effect of methadone maintenance on positive outcomes for opiate injection drug users." Journal of Substance Abuse Treatment 37, no. 2 (September 2009): 120–26. http://dx.doi.org/10.1016/j.jsat.2008.11.004.

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Chang, Kuan-Cheng, Ke-Wei Chen, Chieh-Liang Huang, Wen-Ling Liao, Mei-Yao Wu, Yu-Kai Lin, Yi-Tzone Shiao, Wei-Hsin Chung, Yen-Nien Lin, and Hsien-Yuan Lane. "Association of a Common NOS1AP Variant with Attenuation of QTc Prolongation in Men with Heroin Dependence Undergoing Methadone Treatment." Journal of Personalized Medicine 12, no. 5 (May 20, 2022): 835. http://dx.doi.org/10.3390/jpm12050835.

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Background: The effects of methadone-induced severe prolongation of the corrected QT interval (QTc) and sudden cardiac death appear unpredictable and sex-dependent. Genetic polymorphisms in the nitric oxide synthase 1 adaptor protein (NOS1AP) have been implicated in QTc prolongation in general populations. We investigated whether common NOS1AP variants interact with methadone in relation to QTc prolongation in patients with heroin dependence. Methods: We genotyped 17 NOS1AP variants spanning the entire gene in heroin-dependent patients who received a 12-lead electrocardiography (ECG) examination both at baseline and during maintenance methadone treatment in Cohort 1 and only during maintenance methadone treatment in Cohort 2. The QT interval was measured automatically by the Marquette 12SL program, and was corrected for heart rate using Bazett’s formula. Results: Cohort 1 consisted of 122 patients (age: 37.65 ± 8.05 years, 84% male, methadone dosage: 42.54 ± 22.17 mg/day), and Cohort 2 comprised of 319 patients (age: 36.9 ± 7.86 years, 82% male, methadone dosage: 26.08 ± 15.84 mg/day), with complete genotyping data for analyses. Before methadone, the QTc intervals increased with increasing age (r = 0.3541, p < 0.001); the age-adjusted QTc showed dose-dependent prolongation in men (r = 0.6320, p < 0.001), but abbreviation in women (r = −0.5348, p = 0.018) in Cohort 1. The pooled genotype-specific analysis of the two cohorts revealed that the QTc interval was significantly shorter in male carriers of the rs164148 AA variant than in male carriers of the reference GG genotype (GG: n = 262, QTc = 423 ± 1.4 ms; AA: n = 10, QTc = 404.1 ± 7 ms, p = 0.009), according to univariate analysis. The QTc remained shorter in male carriers of the rs164148 AA variant compared to GG genotype (423 ± 1.4 ms vs. 405.9 ± 6.9 ms, p = 0.016) in multivariate analysis after adjusting for age and methadone dosage. A cut-off QTc interval of <410 ms identifies 100% of AA carriers compared to none of GG carriers when receiving a daily methadone dosage of 30.6 ± 19.3 mg. There was no significant gene-drug interaction in contributing to the adjusted QTc (p = 0.2164) in male carriers of the rs164148 variants. Conclusions: Carriers of a common NOS1AP rs164148 AA genotype variant were associated with a shorter QTc interval in men receiving maintenance methadone treatment. This genetic polymorphism attenuates the QTc-prolonging effect by methadone, and thus may explain at least in part the unpredictable and heterogeneous risks for severe QTc prolongation and sudden cardiac death in patients on methadone.

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Spunt, Barry, Dana E. Hunt, Douglas S. Lipton, and Douglas S. Goldsmith. "Methadone Diversion: A New Look." Journal of Drug Issues 16, no. 4 (October 1986): 569–83. http://dx.doi.org/10.1177/002204268601600406.

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This paper examines the nature and extent of methadone diversion, drawing on interviews and ethnographic data collection with methadone maintenance clients and current narcotics users not in treatment. We explore the social as well as the economic role of diversion in the drug world and find that it is a more complex phenomenon than the simple monetary transaction it is often portrayed to be. Our data indicate that selling or sharing of methadone by methadone clients, though still uncommon, is the primary source of street methadone. We find that removal of take-home dosages from the client population would have deleterious effects on retaining in treatment many otherwise compliant clients and would have minimal effect on diversion. A flexible and differentiated approach might help to reduce diversion while a singular, punitive administrative approach is unlikely to do more than simply contain the situation on the surface and drive it underground.

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Van den Beuken-van Everdingen, MD, PhD, Marieke H. J., José W. Geurts, MSc, and Jacob Patijn, MD, PhD. "Prolonged QT interval by methadone: Relevance for daily practice? A prospective study in patients with cancer and noncancer pain." Journal of Opioid Management 9, no. 4 (July 1, 2013): 263–67. http://dx.doi.org/10.5055/jom.2013.0167.

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Introduction: Increased methadone use in patients with pain has raised concerns that the effect of methadone on the QT interval duration and the potential risk of torsades de pointes (TdP) has been underestimated. Most studies on prolonged QT intervals by methadone are performed in maintenance patients; however, doses of methadone in pain treatment are much lower. Hardly any studies have prospectively addressed QT interval prolongation by methadone in patients with pain, and this study aims to address this literature gap. Methods: In a period of 3 years, while 130 patients used methadone as pain treatment at a stable dose for at least 1 week, 12-lead electrocardiograms (ECGs) were performed. Corrected QT times, demographic features, methadone dose, duration of therapy, and relevant comedication were documented.Results: The findings included 50 percent of 130 patients, with a mean methadone dose of 18.2 mg/d, were potentially at risk for TdP. Beyond this, 5 percent were at definite risk for TdP. No correlations were found between QTc and gender, age, serum potassium or magnesium levels, methadone dose, underlying disease, or comedication.Conclusion: The study found that in our patients with pain, with relatively low doses of methadone, 5 percent had QTc times ≥500 ms and were thus at serious at risk for TdP. ECGs have to be made in all patients with methadone therapy 1 week after introducing methadone (or after dosage increases).

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Peles, Einat, Shaul Schreiber, Tal Hetzroni, Miriam Adelson, and Ruth Defrin. "The Differential Effect of Methadone Dose and of Chronic Pain on Pain Perception of Former Heroin Addicts Receiving Methadone Maintenance Treatment." Journal of Pain 12, no. 1 (January 2011): 41–50. http://dx.doi.org/10.1016/j.jpain.2010.04.009.

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Latham, Linda. "Methadone Treatment in Irish General Practice: Voices of Service Users." Irish Journal of Psychological Medicine 29, no. 3 (2012): 147–56. http://dx.doi.org/10.1017/s0790966700017171.

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AbstractThis study sets out to make a meaningful and useful contribution to the discussion surrounding the treatment of heroin addiction in Ireland. The study took place in nine urban general practices in Dublin city. Twenty five service users were interviewed in-depth. A phenomenological approach drawing on the psychological research methods of Colazzi for data analysis informed this study. Four themes emerged from the data: Service users' the significance of methadone for the service user; service users' understanding of the Methadone Treatment Protocol and the experience of addiction and its effect on families.This paper reports on the experiences of service users receiving methadone treatment in urban general practice in Dublin and in so doing highlights the influence of the GP in supporting recovery. It explores the theme - Service User's Experience of attending general practice for methadone treatment. These accounts provide insight into the harm reduction policy of methadone maintenance and highlight how - from the service users' experience - the implementation is falling short.

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Langleben, Daniel D., Kosha Ruparel, Igor Elman, Samantha Busch-Winokur, Ramapriyan Pratiwadi, James Loughead, Charles P. O’Brien, and Anna R. Childress. "Acute Effect of Methadone Maintenance Dose on Brain fMRI Response to Heroin-Related Cues." American Journal of Psychiatry 165, no. 3 (March 2008): 390–94. http://dx.doi.org/10.1176/appi.ajp.2007.07010070.

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Zhang, Guang, Yuecheng Yang, Runhua Ye, Dapeng Zhang, Duo Shan, Yifei Hu, Bing Dai, and Zhongfu Liu. "Effect of community-based extension clinics of methadone maintenance therapy for opiate-dependent clients." Medicine 97, no. 47 (November 2018): e13323. http://dx.doi.org/10.1097/md.0000000000013323.

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Novick, David M., Mary Jeanne Kreek, Patricia A. Ams, Lisa L. Lau, Stanley R. Yancovitz, and Alvin M. Gelb. "Effect of Severe Alcoholic Liver Disease on the Disposition of Methadone in Maintenance Patients." Alcoholism: Clinical and Experimental Research 9, no. 4 (July 1985): 349–54. http://dx.doi.org/10.1111/j.1530-0277.1985.tb05558.x.

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Prasad, Mona, Susie Lim, Debra Gardner, Leandro Cordero, and Philip Samuels. "619: High dose methadone maintenance (HDMM) and its effect on neonatal abstinence syndrome (NAS)." American Journal of Obstetrics and Gynecology 197, no. 6 (December 2007): S178. http://dx.doi.org/10.1016/j.ajog.2007.10.645.

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37

Joseph, David, Michael J. Schobelock, Robert R. Riesenberg, Bradley D. Vince, Lynn R. Webster, Abidemi Adeniji, Mabrouk Elgadi, and Fenglei Huang. "Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy." Antimicrobial Agents and Chemotherapy 59, no. 1 (November 10, 2014): 498–504. http://dx.doi.org/10.1128/aac.04046-14.

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ABSTRACTThe effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered atClinicalTrials.govunder registration no. NCT01637922.)

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Chawar, Caroul, Alannah Hillmer, Amel Lamri, Flavio Kapczinski, Lehana Thabane, Guillaume Pare, and Zainab Samaan. "Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences." PLOS ONE 16, no. 12 (December 15, 2021): e0261201. http://dx.doi.org/10.1371/journal.pone.0261201.

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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.

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Kovacs, S. J., J. Ke, A. Barve, Y. Cheng, J. Zhang, R. Maietta, G. Sunkara, and D. S. Stein. "840 EFFECT OF THERAPEUTIC DOSES OF ALISPORIVIR (ALV) ON METHADONE PHARMACOKINETICS IN HEALTHY SUBJECTS AND PATIENTS ON STABLE METHADONE MAINTENANCE THERAPY (MMT)." Journal of Hepatology 58 (April 2013): S344—S345. http://dx.doi.org/10.1016/s0168-8278(13)60842-9.

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Tacke, Ulrich, Kim Wolff, Emily Finch, and John Strang. "The effect of tobacco smoking on subjective symptoms of inadequacy (“not holding”) of methadone dose among opiate addicts in methadone maintenance treatment." Addiction Biology 6, no. 2 (April 2001): 137–45. http://dx.doi.org/10.1080/13556210020040217.

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Mollajavadi, Reza, Narges Beyraghi, Isa Fathi, Robab Teymouri, and Arya Hamedanchi. "Retention and Relapse in Methadone Maintenance Treatment: A Descriptive Analytical Study." Global Journal of Health Science 9, no. 2 (June 30, 2016): 15. http://dx.doi.org/10.5539/gjhs.v9n2p15.

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<p><strong>BACKGROUND:</strong> Despite the considerable efforts made in Iran to treat people with addiction, relapse is still common. This study was designed to determine retention and relapse rates and related factors at Yasin Methadone Maintenance Treatment Center.</p><p><strong>PATIENTS & METHODS:</strong> In this study, retention rate, relapse rate, and related factors were examined in 74 cases using a descriptive-analytical method. Information about 20 variables were gathered from patient medical records using an information form and a checklist and data was analyzed by the chi-square, Fisher’s exact, and Mann-Whitney tests using SPSS software.</p><p><strong>FINDINGS:</strong> The retention and relapse rates were 24.3% and 75.7%, respectively. Only three factors showed a significant difference (p<0.50) between the retention and relapse groups: (1) financial status, (2) motivation for treatment, and (3) cooperation during counseling (p=0.04, p=0.001, p=0.026, respectively). No significant differences were observed between groups for the other factors.</p><p><strong>CONCLUSION:</strong> Because it is clear that financial status, motivation, and counseling can affect retention rate, it is recommended to study the effect of these factors on retention using methods such as a randomized clinical trial.</p>

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42

Uhoegbu, Chimdi, Michael Doran, and John O'Connor. "Hypoprolactinaemic galactorrhoea in long-term methadone treatment." Irish Journal of Psychological Medicine 28, no. 2 (June 2011): 100–102. http://dx.doi.org/10.1017/s0790966700011538.

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AbstractAlthough hyperprolactinaemia is associated with galactorrhoea, galactorrhoea often occurs without any hyperprolactinaemia. This has been well established, and it has been documented in women prescribed/using methadone and other opiates. One case series described amenorrhoea and galactorrhoea in ‘female heroin addicts’, but it has not before been described in a patient with hypoprolactinaemia.We report a case of a 30 year old non-pregnant, non-puerperal, opioid-dependent, HIV positive woman on long-term methadone maintenance programme, who presented with bilateral, milky nipple discharge, associated with painful breast lumps, but with serum prolactin levels below the normal range. She was not prescribed any other medications likely to have effect on the endocrine system. This case highlights the need for prescribers to be alert to the implications of long-term use of opioids.

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43

Huang, Shizhen, Cuixian Yang, Jiaying Xin, Ronghui Xie, Xinping Yang, Ruimin Zhang, Xia Li, et al. "Outcomes of Methadone Maintenance Therapy Combined with Rilpivirine/Efavirenz in Treatment-Naive HIV-Infected Patients." Current HIV Research 19, no. 4 (August 30, 2021): 368–76. http://dx.doi.org/10.2174/1570162x19666210423123958.

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Background: Injecting drugs is associated with a high risk of HIV infection, alongside the risk of a drug overdose and mental health problems. Objective: To evaluate the effect of methadone maintenance treatment (MMT) combined with rilpivirine (RPV)-based regimens on drug use of HIV individuals. Methods: This study was a prospective, open-label, controlled, drug-drug interaction trial at a single center for 24 weeks. Participants on stable MMT were randomly divided into two groups administered RPV/TDF/3TC (RPV group) and EFV/TDF/3TC (EFV group), respectively. Adjustment doses of methadone were monitored for 12 weeks. HIV-1 RNA was used to evaluate the effects of antiretroviral therapy at week 24. Acute opioid withdrawal-, drug craving questionnaire- and MOSHIV scales were used to assess study outcomes. Results: 22 and 18 cases of HIV-infected drug users were recruited in the RPV and EFV groups, respectively. Thirty-one cases had completed monitoring and clinical evaluation at week 24. In the RPV and EFV groups, 32% and 56% of the participants had methadone dose adjustment, respectively, indicating a significantly lower rate in the RPV group. The rates of individuals with HIV RNA levels from 50-500 copies/ml were 94% (RPV group) and 90% (EFV group). The drug craving questionnaire scale scores decreased in both groups. After one week of treatments, acute opioid withdrawal scale scores increased in both groups, with no significant difference between them. Conclusion: Concomitant administration of RPV does not significantly affect methadone and could decrease withdrawal symptoms. An RPV-based regimen may be used as first-line treatment in IDUs with HIV infection.

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44

Garimella, T., R. Wang, W. L. Luo, P. Wastall, H. Kandoussi, M. DeMicco, R. D. Bruce, C. Hwang, R. Bertz, and M. Bifano. "Assessment of Drug-Drug Interactions between Daclatasvir and Methadone or Buprenorphine-Naloxone." Antimicrobial Agents and Chemotherapy 59, no. 9 (June 29, 2015): 5503–10. http://dx.doi.org/10.1128/aac.00478-15.

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ABSTRACTHepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg;n= 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg;n= 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (Cmax) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- andS-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ forR-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24),S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalizedCmaxfor both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments.

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45

Nejati, V. "P03-244 - Effect of methadone maintenance therapy on selective attention and drug related attention bias." European Psychiatry 25 (2010): 1311. http://dx.doi.org/10.1016/s0924-9338(10)71298-0.

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46

van Ameijden, E. J. C., M. W. Langendam, and R. A. Coutinho. "Dose-effect relationship between overdose mortality and prescribed methadone dosage in low-threshold maintenance programs." Addictive Behaviors 24, no. 4 (July 1999): 559–63. http://dx.doi.org/10.1016/s0306-4603(98)00083-5.

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47

Akbari, Parastoo, Mahmoud Najafi, Ali-Mohammad Rezaei, and Hossein Miladi-Gorji. "Enriched Environment Ameliorates Cognitive Deficits and Locomotor Sensitization in Morphine-Withdrawn Rats Receiving Methadone Maintenance Treatment." Neuropsychobiology 79, no. 6 (2020): 437–44. http://dx.doi.org/10.1159/000506598.

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<b><i>Objective:</i></b> This study was designed to examine whether enriched environments (EE) would attenuate object recognition and spatial learning and memory deficits and locomotor sensitization induced by methadone maintenance treatment (MMT) in morphine-withdrawn rats. <b><i>Methods:</i></b> Male Wistar rats (170 ± 10 g) were injected with bi-daily doses (10 mg/kg, 12-h intervals) of morphine for 14 days. Rats receiving MMT were reared in the standard environment (SE) or EE during 30 days of morphine withdrawal. Then, the rats were tested for object recognition (the object recognition memory test, ORMT) and spatial learning and memory (the water maze) and then challenged with morphine (1 mg/kg, i.p.) and evaluated for locomotor activity (open-field box). <b><i>Results:</i></b> The results revealed that the dependent/saline/EE (D/Sal/EE) and D/methadone/EE (D/Meth/EE) rats exhibited significant preference for the new object (<i>p</i> = 0.006 and <i>p</i> = 0.049), spent more time in the target zone (<i>p</i> = 0.045 and <i>p</i> = 0.005) on the water maze, and displayed a lower level of distance traveled (<i>p</i> = 0.002 and <i>p</i> = 0.0001) compared to their control groups reared in SE. <b><i>Conclusions:</i></b> We conclude that exposure to EE could ameliorate the object recognition and spatial memory deficits and also decrease locomotor sensitivity in morphine-withdrawn rats receiving MMT. Thus, EE may be beneficial in the treatment of addiction during MMT.

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48

Simangunsong, Dian Natalya, Juanita, and Kintoko Rochadi. "The Effect of Patients’ Characteristics and the Dosage of Methadone Maintenance on Retention of Methadone Therapy in H. Adam Malik General Hospital, Medan." Indonesian Journal of Medicine 4, no. 2 (2019): 176–82. http://dx.doi.org/10.26911/theijmed.2019.04.02.11.

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49

Ghodse, A. H., T. H. Bewley, M. K. Kearney, and S. E. Smith. "Mydriatic Response to Topical Naloxone in Opiate Abusers." British Journal of Psychiatry 148, no. 1 (January 1986): 44–46. http://dx.doi.org/10.1192/bjp.148.1.44.

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Naloxone hydrochloride eyedrops 1 mg/ml dilated the pupils of 36 out of 47 opiate addicts on methadone maintenance treatment, without precipitation of acute withdrawal effects, but not those of healthy unmedicated subjects. The response in addicts was attenuated by certain ancillary treatments and by withdrawal of methadone treatment. The size of the response suggests some potential clinical use for topical naloxone as a diagnostic test of current opioid influence and possibility of physical dependence. The local mydriatic response, which was restricted to the treated eye, indicates that the effect of opiates on the pupil in man is determined, at least in part, by a peripheral action.

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Bates, M., and D. A. Pemberton. "The Effect of Methadone Prescribing in a Clinic Setting on the Criminal Activity of Drug Users." Scottish Medical Journal 41, no. 6 (December 1996): 173–75. http://dx.doi.org/10.1177/003693309604100606.

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The objective was to examine the impact of clinic attendance and methadone prescribing on drug user criminality. Fifty-four consecutive attenders at a Drug Problem Clinic were interviewed by questionnaire. An objective assessment of the criminality on 49(91%) of the above was made by examining their conviction details, before and after clinic attendance. Seventy-seven per cent strongly agreed that fewer criminal charges had been preferred since attendance at the clinic had begun and drugs prescribed. No statistically significant difference was found in the conviction numbers for the group as a whole: mean 3.9 (before) to 3.2 (after): p=0.24, or for the females in particular: mean 2.8 (before) to 5.9 (after): p=0.97. There was, however, a significant drop in the number of convictions amongst the males: mean 4.3 (before) to 2.5 (after): p=0 02. This study confirms an association between methadone maintenance therapy in a clinic setting and a reduction in criminality amongst males.

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