9 November 2014

Something old / something new. Harm reduction in action for hepatitis C infection.

Dear Colleagues,
I have been sent several articles recently pertaining to dependency treatment and hepatitis C (HCV) - see below for citations and additional comments. 
Unsurprisingly, a 2014 Cochrane summary concurs with our own experience that methadone and buprenorphine are highly effective drugs for opiate maintenance with methadone having somewhat better statistics on retention.  While maintenance research for 40 years has shown reduced injecting, it is gratifying that this has finally translated into lower rates of HCV transmission - see two further items below.  Once again, opiate maintenance seems to be worth the expense and the indignities and should probably be mainstream medical practice which would eliminate current long waiting lists. 
A regrettable ‘guideline’ in the Pain journal advises first relating possible cardiac side effects to prospective methadone patients and then performing ECG before and during treatment despite a frank admission that such strategies are not evidence based.  [Cochrane finds ‘no evidence’ for ECG as a preventive strategy]
Finally and left of field, Mason shows evidence favouring agonist treatment for alcoholism (using gabapentin in this case), at least in a 12 week RCT. 
Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 Feb 6
White B, Dore GJ, Lloyd AR, Rawlinson WD, Maher L. Opioid substitution therapy protects against hepatitis C virus acquisition in people who inject drugs: the HITS-c study. Med J Aust 2014 201;6:326-329
Tsui JI, Evans JL, Lum PJ, Hahn JA, Page K. Association of Opioid Agonist Therapy With Lower Incidence of Hepatitis C Virus Infection in Young Adult Injection Drug Users. JAMA Intern Med. 2014 Oct 27
Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med 2014 174;1:70-77      
Methadone Safety Guidelines. Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Society. Chou R, Cruciani RA, Fiellin DA, Compton P, Farrar JT, Haigney MC, Inturrisi C, Knight JR, Otis-Green S, Marcus SM, Mehta D, Meyer MC, Portenoy R, Savage S, Strain E, Walsh S, Zeltzer L. The Journal of Pain 2014 15;4:321-337
Our own practice has been doing hepatitis monitoring every six months for the past 25 years in our OTP patients.  As with other reports, we have seen a steady decline in the rate of HCV in new patients plus a small number of new cases, even in those already in treatment.  One was a re-infection after treatment while another had two different genotypes.  About 50 have been treated with interferon and ribavirin with about 80% achieving sustained viral response and thus cure of the disease.  Five others (10%) were successfully treated on a second episode, using triple anti-viral therapy. 
White et al. and Tsui et al. have used longitudinal studies of drug using volunteers with regular testing for HCV antibodies and pcr (virus).  Whites paper describes the dramatic reduction in overall incidence from 30 cases per 100 patient years in some older studies to 8 cases in their data from Central and Western Sydney (n=150, t=3yrs).  For those with recent engagement in opiate maintenance treatment this rate was almost 6 fold lower, approximately one single case (still one too many).  Tsui and colleagues (n=550, t=6yrs) found a high rate of 25 cases per 100 pt yrs in Boston/Californian injectors, but a far lower rate in the sub-group reporting recent opiate maintenance treatment (about half), consistent with White’s findings from Sydney.  Both studies had high rates of homeless and unemployed subjects. 
Mason has published about the use of nalmefene in alcoholism 15 years ago with this recent contribution a RCT of gabapentin which increased abstinence from 4% to 17% at 12 weeks using 1800mg daily.  However, even on the full dose, less than one fifth of patients became abstinent (all patients received counselling).  For moderate drinking, the modest placebo effect was doubled but over half the patients still failed to respond.  A major question is whether the responders are the same or a different group to the responders to anti-craving drugs or Antabuse. 
One must admire Mason with the staying power to examine such diverse interventions in fields in which there are still very limited options.  She has also looked at gabapentin in cannabis withdrawals in 2012.  There have also been some promising items by others relating to the use of baclofen, topiramate and ondansetron.  These should all be subject of serious research considering the scope of the problem.  The most effective intervention I have read actually gave alcohol to homeless alcoholics in Toronto (http://methadone-research.blogspot.com.au/2006/01/supplying-alcohol-to-alcoholics-may_9924.php4). 
There has still been poor general uptake for the three approved drugs for alcoholism, disulfiram, naltrexone and acamprosate despite proven benefits in a substantial proportion of alcohol dependent patients (when used in a structured program).  In a world driven by quick profits from avaricious drug manufacturers (see stories about Gilead on hepatitis C tablets marketed at $1000 per pill!) research on drugs which are already approved is unlikely without pressure from health officials, politicians and other advocates.  For rare diseases one might understand high prices to return funds spent on research.  For common diseases like hepatitis C and alcoholism profiteering can verge on the criminal in my view. 
Last but not least is one of the least productive (unless you hold Reckitt stocks) items I have read, a guideline on methadone prescription.  My more detailed summary is on (http://methadone-research.blogspot.com.au/2014/11/a-disappointing-guideline-on-methadone.html ). 
There may be a case to examine the long term side effects of methadone (for example on calcium metabolism and androgen suppression) and try to balance this with a transfer to buprenorphine in suitable cases as a means of preventing future problems.  However, these authors only deal with one exceedingly rare non-fatal cardiac event, while ignoring the cardiac benefits attributed to methadone by Mori Krantz in 2001 (http://methadone-research.blogspot.com.au/2013/10/archive-of-mori-krantz-article-on.html ).  This article in ‘Pain’ appears to exaggerate the cardiac side effects of methadone while also using speculative advice on ECGs as prevention.  Tachycardia is a very unpleasant event but nowhere is it mentioned that there has never been a death in a methadone patient due to confirmed torsade de pointes in 50 years. 
Best regards to my readers and congratulations for your patience in reaching this point in my humble narrative. 
Andrew Byrne ..