12 February 2017

Lower mortality and better retention in OTP patients prescribed benzos.

Bakker A, Streel E. Benzodiazepine maintenance in opiate substitution treatment: Good or bad? A retrospective primary care case-note review. Journal of Psychopharmacology 2016 1-5
Dear Colleagues,
Finally we have some strong evidence that prescribing benzodiazepines for patients on opiate maintenance treatment is not only safe and effective but in some cases may be obligatory, under careful supervision with adequate psychosocial supports. 
Dr Bakker in London has done us the great service of publishing the data he has extracted from his own general practice from over 20 years of caring for drug dependent patients.  His practice is based on sound harm reduction principles, prescribing long acting, low potency benzodiazepines such as diazepam or clonazepam using graduated supervision for dependent patients.  In this he bucked the trend based on what he considered good medical practice, albeit non-evidence based (like much prescribing practice). 
Bakker reports on 278 OTP patients since 1998 (1289 patient/treatment years) comprising a high proportion of socio-economically deprived citizens, two thirds being male.  Regarding prescription for benzodiazepines (bzd) from the practice, patients were classified ‘never prescribed bzd’, ‘occasional prescription bzd’ and ‘maintenance bzd.  Further, he examined those still in treatment against those who had departed (96% still in UK, 4% gone overseas, lost to follow-up).  From comprehensive statistics kept by the British NHS Bakker was able to derive accurate mortality figures for these six groups with surprising results for retention and mortality. 
Never              Occasional       Maintenance
Current pats:   223t/y              301t/y              765t/y  
Mortality:        1.79p100ty      0.33p100ty     1.31p100ty
Retention        34 months       51 months       72 months      
Ex-patients:     267t/y              320t/y              305t/y
Mortality:        2.24 p100t/y    0.63 p100t/y   5.90 p100t/y
Excess mort:    125%               191%               450%
T/y = treatment years
Contrary to some expectations, retention was highest in the group prescribed maintenance benzodiazepines.  Furthermore, mortality was lower than in the group never prescribed sedatives and the lowest mortality was intriguingly in those occasionally prescribed sedatives.  However, the most meaningful, and very worrying statistic is the high mortality in maintenance patients who transferred elsewhere for their treatment (more than 4 fold those remaining in treatment at Dr Bakker’s practice in London).  The authors report that following health authority directives very few maintenance prescribers in the UK allow benzodiazepine prescription in parallel as Dr Bakker’s practice does.  Hence the likely inference that these patients had legal supplies of benzodiazepines curtailed on transferring elsewhere for their OTP treatment. 
Another important finding was that the death rates were lowest, and very significantly lower, in those prescribed benzos occasionally, both in-house patients and in those transferred elsewhere. 
This report is not a randomised controlled trial, nor was it prospective, yet it involves large numbers of patients in a normal medical population over a long period with very few lost to follow-up (4%).  Hence the findings are very meaningful for those involved in comparable practice providing opiate maintenance with methadone and/or buprenorphine in a community setting. 
From this paper is it apparent that withdrawing benzodiazepines may increase mortality substantially.  Hence, official guidelines and clinical recommendations which warn against benzodiazepine prescription may be contributing to excess deaths rather than preventing them.  In my experience most OTP prescribers have a small number of patients who are prescribed benzodiazepines, some long-term.  Yet up to 70% of our patients have had problems with sedatives and so to ignore this and advise: ‘just say no’ may not be the proper approach.  However, prescribing is well beyond the comfort zone for many in our field without formal protocols. 
It is my view that all dependent patients should be able to access benzodiazepines under some clinical framework although this should not be open-ended, just like methadone.  There should be dose supervision initially ranging to normal unsupervised prescription for those who are socially integrated but unable or unwilling to cease sedative use.  Those abusing alcohol should be excluded until they can demonstrate abstinence.  Trial dose reductions should be negotiated periodically, as with methadone.  In our own practice we use diazepam and we aim to a dose of 4-15mg daily which is satisfactory for the great majority after initial reductions. 
Notes by Andrew Byrne ..
Bakker article PDF:
References: Franklyn AM, Eibl JK, Gauthier G, Pellegrini D, Lightfoot NK, Marsh DC. The impact of benzodiazepine use in patients enrolled in opioid agonist therapy in Northern and rural Ontario. Harm Reduction Journal 2017 14:6
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