29 June 2010

Should we be giving supervised Valium reductions or even maintenance? 2 recent papers.

Agonist substitution - a treatment alternative for high-dose benzodiazepine-dependent patients? Liebrenz M, Boesch L, Stohler R, Caflisch C. Addiction. 2010 Apr 27 Early View

Benzodiazepine use among heroin users: Baseline use, current use and clinical outcome. Darke S, Ross J, Mills K, Teesson M, Williamson A, Harvard A. D&A Review 2010 29:3:250-255

Dear Colleagues,

Two prominent recent articles have highlighted an often neglected problem area for drug users in treatment. Benzodiazepine use/abuse has long been the ‘elephant in the room’ in addiction treatment. It is surprising to me that a ‘Just-say-no’ approach is often espoused for this particular problem where ‘harm reduction’ is the principle underlying public health and medical treatment in recent years. Yet we know that benzos, along with alcohol, constitute a major source of harm in the drug using population.

Darke and colleagues report that tranquillizer use parallels both physical and mental deterioration. This 3 year, prospective longitudinal study finds that initial use of benzodiazepines did not, however, predict poor progress in the medium to long term. Their study group included patients entering pharmacotherapy, detoxification and rehabilitation services as well as a non-treatment group recruited from community harm reduction services (needle services).

It is possible that much of this harm may be preventable given an appropriate approach. Benzodiazepines also feature prominently as an association in mortality reports by Darke and others.

In an editorial in Addiction, some Swiss workers propose ‘agonist substitution’ as a hypothesis which needs formal testing. They point out the differences with methadone maintenance as well as some similarities. They further detail possible problems, especially with shorter acting or injectable preparations. However, they also emphasise the known dangers of ignoring this issue when, despite current interventions, a high proportion of users remain unable or unwilling to withdraw from these drugs. From reports over many years we know that there is a wide regional variation in use with relatively low levels in some American cities (<10% dependent) up to very high levels reported in Israel (>50% in some clinic populations).

Over the years I have interviewed many clinicians about the question of prescribing benzodiazepines to dependent patients. My findings have been that the great majority of experienced clinic doctors have authorised supervised dispensing of long acting benzodiazepines, usually diazepam, in short or medium term use for at least some patients. Most, however, have been reluctant to do so long-term or for large numbers of patients in the absence of clear guidelines on the subject.

This lack of an accepted protocol is partly due to a lack of research evidence. Yet benzodiazepines, like opiates, are still prescribed widely in the general population for insomnia, anxiety and panic disorders, even if their use is not first line. Hence we should ensure that we strike the right balance between discouraging their use and making them available in a manner which is safe. Only a very small proportion of those who are prescribed benzodiazepines develop dependency problems, precisely as also occurs with opioids for pain. Overall sedative prescribing has dropped significantly over the years but some preparations have seen surges in recent years such as alprazolam. Flunitrazepam has been subject to certain restrictions in Australia and was never been approved/marketed in the United States.

There is no dispute about the use of diazepam in alcohol withdrawal, status epilepticus and panic disorders (see various expert guidelines). While its effectiveness for insomnia and anxiety is limited by tolerance, most GPs still use benzodiazepine prescription in some cases. Hence there is a case for benzodiazepine availability in dependency clinics, even if just to avoid prescription of large quantities unsupervised from other doctors. Whether this should be available low-term or high-dose is still controversial. Yet such a practice could be seen potentially as a “harm minimization”, knowing that quite the opposite can easily occur with community prescribing of unsupervised or “on demand” prescriptions.

Thus smaller quantities and increased supervision may be consistent with improvements to measurable indices of stability in dual addicted patients. The safest would be one tablet per day with all tablets being supervised … yet this may not be acceptable to some patients and may not be practicable in the clinic/pharmacy setting. It is certainly a time consuming enterprise and could not possibly be offered to large numbers of patients without specific funding. And such funding is unlikely to be provided without more formal research to demonstrate safety and effectiveness of such an approach.

Comments by Andrew Byrne ..