1. Med J Aust. 2009 Sep 21;191(6):302-3.
Improving the management of chronic non-malignant pain and reducing problems associated with prescription opioids.
Wodak AD, Cohen ML, Dobbin MD, Hallinan RA, Osborn M.
St. Vincent's Hospital, Sydney, NSW, Australia. awodak@stvincents.com.au
New guidelines and a multidisciplinary approach have the potential to help patients in need while minimising inappropriate use of opioids.
PMID: 19769550 [PubMed - indexed for MEDLINE]
http://www.mja.com.au/public/issues/191_06_210909/wod10633_fm.html
2. Eur J Clin Pharmacol. 2009 Nov;65(11):1113-20. Epub 2009 Jul 29.
Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study.
Hallinan R, Crettol S, Agho K, Attia J, Besson J, Croquette-Krokar M, Hämmig R, Déglon JJ, Byrne A, Ray J, Somogyi AA, Eap CB.
The Byrne Surgery, Redfern, NSW, Australia.
PURPOSE: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. METHODS: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose.
RESULTS: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4.
CONCLUSION: Cannabis use and higher methadone doses in MMT could in part be a response to-or a cause of-more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.
PMID: 19639308 [PubMed - indexed for MEDLINE]
3. J Sex Med. 2008 Mar;5(3):684-92. Epub 2007 Dec 18.
Erectile dysfunction in men receiving methadone and buprenorphine maintenance treatment.
Hallinan R, Byrne A, Agho K, McMahon C, Tynan P, Attia J.
The Byrne Surgery, Redfern, Sydney, NSW, Australia. reichall@iprimus.com.au
INTRODUCTION: Use of opiates/opioids is associated with hypoactive sexual desire, erectile and orgasmic dysfunction. AIM: To determine prevalence and investigate etiology of sexual dysfunction in men on methadone or buprenorphine maintenance
treatment (MMT, BMT).
MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF), hormone assays, Beck Depression Inventory. METHODS: A total of 103 men (mean age 37.6 +/- 7.9) on MMT (N = 84) or BMT (N = 19) were evaluated using the IIEF, hormone assays, Beck Depression Inventory, body mass index (BMI), demographic, and other substance use measures.
RESULTS: Mean total IIEF scores for partnered men were lower for MMT (50.4 +/- 18.2; N = 53) than reference groups (61.4 +/- 16.8; N = 415; P < 0.0001) or BMT (61.4 +/- 7.0; N = 14; P = 0.048). Among partnered men on MMT, 53% had erectile dysfunction (ED) compared with 24% of reference groups; 26% had moderate to severe ED, 12.1% in under 40s and 40.0% among those 40+ years. On multiple regression, depression, older age, and lower total testosterone were associated with lower IIEF and EF domain; on multivariate analysis, there were no significant associations between IIEF or EF and free testosterone, opioid dose, cannabis or other substance use, viral hepatitis, or BMI. Total testosterone accounted for 16% of IIEF and 15% of EF variance. Men without sexual partners had lower Desire and Erection Confidence scores and less recent sexual activity, suggesting potentially higher prevalence of sexual dysfunction in this group.
CONCLUSION: Men on MMT, but not BMT, have high prevalence of ED, related to hypogonadism and depression. Practitioners should screen for sexual dysfunction in men receiving opioid replacement treatment. Future studies of sexual dysfunction in opioid-treated men should examine the potential benefits of dose reduction, androgen replacement, treatment of depression, and choice of opioid.
PMID: 18093096 [PubMed - indexed for MEDLINE]
4. Int J Androl. 2009 Apr;32(2):131-9. Epub 2007 Oct 30.
Hypogonadism in men receiving methadone and buprenorphine maintenance treatment.
Hallinan R, Byrne A, Agho K, McMahon CG, Tynan P, Attia J.
The Byrne Surgery, Redfern, NSW, Australia. reichall@iprimus.com.au
The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement.
PMID: 17971165 [PubMed - indexed for MEDLINE]
