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). White’s 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 ..
Clinic web page: http://methadone-research.blogspot.com/
